Weiterführende Literatur zum Lehrbuch „Biochemie“ (Kapitel 4 – 50) Im Buch ist aus Platzgründen auf die Angabe weiterführender Literatur verzichtet worden. Auskünfte zu den thematischen Schwerpunkten der vier Hauptteile II bis V geben die im Folgenden aufgeführten knapp 1000 einschlägigen Artikel aus wissenschaftlichen Fachzeitschriften. Die Zusammenstellung von Dr. Heike Angerer folgt der Gliederung des Buchs. Über die Lesezeichen-Darstellung (links) können Sie direkt zur Literatur der einzelnen Kapitel springen, aber es ist stets auch die gesamte Literatur hinterlegt (z.B. für einen kompletten Ausdruck). Die Aufstellung enthält überwiegend Review-Artikel der letzten 4 Jahre, in denen der aktuelle Kenntnisstand zu einem ausgewählten Thema von führenden Wissenschaftlern präsentiert wird. Beim Einführungsteil (Kapitel 1 bis 3) haben wir dagegen bewusst auf Spezialliteratur verzichtet; hier sei auf einschlägige Lehrbücher der Biochemie, Molekularbiologie, Genetik und Zellbiologie, die diesen fundamentalen Aspekten breiten Raum widmen, verwiesen. Falls Sie als Leser interessante Artikel finden, die unsere Literatursammlung ergänzen und bereichern könnten, bitten wir um kurze Mitteilung an den Verlag. Werner Müller-Esterl (für die Autoren)Heike Angerer (Bearbeitung für die 2. Auflage)

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Teil II Struktur und Funktion von Proteinen

4 Proteine – Werkzeuge der Zelle

4.1 Liganden binden an Proteine und verändern deren Konformation

Wilson MA, Brunger AT (2000) The 1.0 Å crystal structure of Ca2+-bound calmodulin:

an analysis of disorder and implications for functionally relevant plasticity, J Mol Biol

301, 1237-1256

O'Day DH & Myre MA (2004) Calmodulin-binding domains in Alzheimer's disease

proteins: extending the calcium hypothesis. Biochemical and Biophysical Research

Communications, 320, 1051-1054.

4.2 Enzyme binden Substrate und setzen sie zu Produkten um

Showalter AK & Tsai MD (2002) A reexamination of the nucleotide incorporation

fidelity of DNA polymerases. Biochemistry, 41, 10571-10576.Johnson KA (2008)

Role of induced fit in enzyme specificity: A molecular forward/reverse switch. Journal

of Biological Chemistry, 283, 26297-26301.

4.3 Liganden kommunizieren über allosterische Effekte

Ridge KD et al (2003) Phototransduction: crystal clear, Trends Biochem Sci 28, 479-

487

Villaverde A (2003) Allosteric enzymes as biosensors for molecular diagnosis. Febs

Letters, 554, 169-172.

Ascenzi P & Fasano M (2010) Allostery in a monomeric protein: The case of human

serum albumin. Biophysical Chemistry, 148, 16-22.

4.4 Die Bindung und Hydrolyse von Nucleotiden steuert Motorproteine

Tomkiewicz D, Nouwen N, & Driessen AJM (2007) Pushing, pulling and trapping -

Modes of motor protein supported protein translocation. Febs Letters, 581, 2820-

2828.

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Enernark EJ & Joshua-Tor L (2008) On helicases and other motor proteins. Current

Opinion in Structural Biology, 18, 243-257. (PDF)

4.5 Regulatorproteine werden oft über Phosphorylierung gesteuert

Johnson LN (2009) The regulation of protein phosphorylation. Biochemical Society

Transactions, 037, 627-641.

Bradshaw JM (2010) The Src, Syk, and Tec family kinases: Distinct types of

molecular switches. Cellular Signalling, 22, 1175-1184.

4.6 Enzyme passen sich metabolischen Bedürfnissen an

Roach PJ (2002) Glycogen and its metabolism, Curr Mol Med 2, 101-120

4.7 Proteine können auf mechanische Spannung reagieren

Tsunozaki M & Bautista DM (2009) Mammalian somatosensory

mechanotransduction. Current Opinion in Neurobiology, 19, 362-369.

Arnadottir J & Chalfie M (2010) Eukaryotic Mechanosensitive Channels. Annual

Review of Biophysics, Vol 39, 39, 111-137.

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5 Ebenen der Proteinarchitektur

5.1 Die Proteinstruktur ist hierarchisch gegliedert

Liu M, Grigoriev A (2004) Protein domains correlate strongly with exons in multiple

eukaryotic genomes - evidence of exon shuffling?, Trends Genet 20, 399-403

Thomas A, Joris B, & Brasseur R (2010) Standardized evaluation of protein stability.

Biochimica et Biophysica Acta-Proteins and Proteomics, 1804, 1265-1271.

5.2 Aminosäuren werden zu Polypeptidketten verknüpft

Tamura K, Alexander RW (2004) Peptide synthesis through evolution, Cell Mol Life

Sci 61, 1317-1330

Rohde H & Seitz O (2010) Ligation-Desulfurization: A Powerful Combination in the

Synthesis of Peptides and Glycopeptides. Biopolymers, 94, 551-559.

Belousoff MJ, Davidovich C, Zimmerman E, Caspi Y, Wekselman I, Rozenszajn L,

Shapira T, Sade-Falk O, Taha L, Bashan A, Weiss MS, & Yonath A (2010) Ancient

machinery embedded in the contemporary ribosome. Biochemical Society

Transactions, 38, 422-427.

5.3 Polypeptide können nach ihrer Synthese modifiziert werden

Jensen ON (2004) Modification-specific proteomics: characterization of post-

translational modifications by mass spectrometry, Curr Opin Chem Biol 8, 33-41

Freitas MA, Sklenar AR, & Parthun MR (2004) Application of mass spectrometry to

the identification and quantification of histone post-translational modifications.

Journal of Cellular Biochemistry, 92, 691-700. (PDF)

5.4 Planare Peptidbindungen bilden das Rückgrat der Proteine

Takahashi K, Uchida C, Shin RW, Shimazaki K, & Uchida T (2008) Prolyl isomerase,

Pin1: new findings of post-translational modifications and physiological substrates in

cancer, asthma and Alzheimer's disease. Cellular and Molecular Life Sciences, 65,

359-375.

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5.5 Die α-Helix ist ein prominentes Sekundärstrukturelement

Chiang D, Joshi AK, & Dill KA (2006) A grammatical theory for the conformational

changes of simple helix bundles. Journal of Computational Biology, 13, 21-42.

5.6 β-Faltblätter und β-Schleifen bilden ausgedehnte Sekundärstrukturen

Khakshoor O & Nowick JS (2008) Artificial beta-sheets: chemical models of beta-

sheets. Current Opinion in Chemical Biology, 12, 722-729. (PDF)

5.7 Sekundärstrukturelemente bilden wiederkehrende Motive

Watanabe M, Kobashigawa Y, Aizawa T, Demura M, & Nitta K (2004) A non-native

alpha-helix is formed in the beta-sheet region of the molten globule state of canine

milk lysozyme. Protein Journal, 23, 335-342.

5.8 Nichtkovalente Wechselwirkungen stabilisieren die Tertiärstruktur

Boas FE & Harbury PB (2007) Potential energy functions for protein design. Current

Opinion in Structural Biology, 17, 199-204.

5.9 Globuläre Proteine falten sich zu kompakten Strukturen

Frauenfelder H et al (2003) Myoglobin: the hydrogen atom of biology and a paradigm

of complexity, Proc Natl Acad Sci U S A 100, 8615-8617. (PDF)

Elber R (2010) Ligand diffusion in globins: simulations versus experiment. Current

Opinion in Structural Biology, 20, 162-167.

5.10 Mehrere Untereinheiten bilden die Quartärstruktur der Proteine

Brinda KV, Surolia A, & Vishveshwara S (2005) Insights into the quaternary

association of proteins through structure graphs: a case study of lectins. Biochemical

Journal, 391, 1-15. (PDF)

Rosenzweig R & Glickman MH (2008) Chaperone-driven proteasome assembly.

Biochemical Society Transactions, 36, 807-812.

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5.11 Proteine falten schrittweise in ihre native Konformation

Dobson CM (2003) Protein folding and misfolding, Nature 426, 884-890

Foguel B & Silva JL (2004) New insights into the mechanisms of protein misfolding

and aggregation in amyloidogenic diseases derived from pressure studies.

Biochemistry, 43, 11361-11370.

Ito K & Inaba K (2008) The disulfide bond formation (Dsb) system. Current Opinion in

Structural Biology, 18, 450-458.

Bandopadhyay R & de Belleroche J (2010) Pathogenesis of Parkinson's disease:

emerging role of molecular chaperones. Trends in Molecular Medicine, 16, 27-36.

5.12 Proteine können reversibel denaturieren

May BC et al (2004) Prions: so many fibers, so little infectivity, Trends Biochem Sci

29, 162-165

Oberhauser AF & Carrion-Vazquez M (2008) Mechanical biochemistry of proteins

one molecule at a time. Journal of Biological Chemistry, 283, 6617-6621. (PDF)

Perrin RJ, Fagan AM, & Holtzman DM (2009) Multimodal techniques for diagnosis

and prognosis of Alzheimer's disease. Nature, 461, 916-922.

5.13 Proteine können maßgeschneidert werden

Georlette D et al (2004) Some like it cold: biocatalysis at low temperatures, FEMS

Microbiol Rev 28, 25-42

Tian J & Xie ZJ (2008) The Na-K-ATPase and calcium-signaling microdomains.

Physiology, 23, 205-211. (PDF)

Wang HX, Nakata E, & Hamachi I (2009) Recent Progress in Strategies for the

Creation of Protein-Based Fluorescent Biosensors. Chembiochem, 10, 2560-2577.

Omenetto FG & Kaplan DL (2010) New Opportunities for an Ancient Material.

Science, 329, 528-531.

Cartellieri M, Bachmann M, Feldmann A, Bippes C, Stamova S, Wehner R, Temme

A, & Schmitz M (2010) Chimeric Antigen Receptor-Engineered T Cells for

Immunotherapy of Cancer. Journal of Biomedicine and Biotechnology. (PDF)

6 Proteine auf dem Prüfstand

6.1 Proteine müssen für die Aufreinigung in wässriger Lösung vorliegen

Bowie JU (2001) Stabilizing membrane proteins, Curr Opin Struct Biol 11, 397-402

Seddon AM, Curnow P, & Booth PJ (2004) Membrane proteins, lipids and

detergents: not just a soap opera. Biochimica et Biophysica Acta-Biomembranes,

1666, 105-117.

6.2 Die Gelfiltrationschromatographie trennt Proteine nach ihrer Größe

Winzor DJ (2003) The development of chromatography for the characterization of

protein interactions: a personal perspective, Biochem Soc Trans 31, 1010-1014

Berek D (2010) Size exclusion chromatography - A blessing and a curse of science

and technology of synthetic polymers. Journal of Separation Science, 33, 315-335.

6.3 Die Ionenaustauschchromatographie trennt Proteine unterschiedlicher Ladung

Stahlberg J (1999) Retention models for ions in chromatography, J Chromatogr A

855, 3-55

Jungbauer A & Hahn R (2009) Ion-Exchange Chromatography. Guide to Protein

Purification, Second Edition, 466, 349-371.

6.4 Die Affinitätschromatographie nutzt die spezifischen Bindungseigenschaften von Proteinen

Vikis HG, Guan KL (2004) Glutathione-S-transferase-fusion based assays for

studying protein-protein interactions, Methods Mol Biol 261, 175-86

Lee WC, Lee KH (2004) Applications of affinity chromatography in proteomics, Anal

Biochem 324, 1-10

Urh M, Simpson D, & Zhao K (2009) Affinity Chromatography: General Methods.

Guide to Protein Purification, Second Edition, 466, 417-438.

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6.5 Die Elektrophorese analysiert Proteingemische qualitativ

Kleparnik K & Bocek P (2010) Electrophoresis today and tomorrow: helping

biologists' dreams come true. Bioessays, 32, 218-226.

6.6 Die isoelektrische Fokussierung trennt Proteine nach Neutralpunkten

Van den Bergh G, Arckens L (2004) Fluorescent two-dimensional difference gel

electrophoresis unveils the potential of gel-based proteomics, Curr Opin Biotechnol

15, 38-43

Barnouin K (2004) Two-dimensional gel electrophoresis for analysis of protein

complexes, Methods Mol Biol 261, 479-98

Zilberstein G, Bukshpan S, & Righetti PG (2010) Third generation of focusing: Gel

matrices with immobilized cation gradients. Electrophoresis, 31, 1747-1753.

6.7 Antikörpersonden identifizieren Proteine

Shaw CE, Zheng J (1998) Western immunoblot analysis, Methods Mol Biol 105, 295-

306

Ahmed FE (2002) Detection of genetically modified organisms in foods, Trends

Biotechnol 20, 215-223

Kurien BT & Scofield RH (2009) A brief review of other notable protein detection

methods on blots. Methods Mol Biol, 536.

6.8 Enzymimmuntests quantifizieren Proteine in komplexen Gemischen

Plested JS et al (2003) ELISA, Methods Mol Med 71, 243-61

6.9 Die Fluoreszenzmikroskopie lokalisiert Proteine in Zellen

Huang B, Bates M, & Zhuang XW (2009) Super-Resolution Fluorescence

Microscopy. Annual Review of Biochemistry, 78, 993-1016. (PDF)

7 Die Erforschung der Proteinstruktur

7.1 Die Edman-Sequenzierung entziffert die Primärstruktur eines Proteins

Grant GA et al (1997) Edman sequencing as tool for characterization of synthetic

peptides, Methods Enzymol 289, 395-419

7.2 Die chemische Synthese von Peptiden erfolgt im Merrifield-Verfahren

Merrifield B (1997) Concept and early development of solid-phase peptide synthesis,

Methods Enzymol 289, 3-13

Marasco D, Perretta G, Sabatella M, & Ruvo M (2008) Past and Future Perspectives

of Synthetic Peptide Libraries. Current Protein & Peptide Science, 9, 447-467.

7.3 Die Massenspektrometrie bestimmt exakt Protein- und Peptidmassen

Steen H, Mann M (2004) The ABC's (and XYZ's) of peptide sequencing, Nat Rev Mol

Cell Biol 5, 699-711

Bergeron JJM, Au CE, Desjardins M, McPherson PS, & Nilsson T (2010) Cell biology

through proteomics - ad astra per alia porci. Trends in Cell Biology, 20, 337-345.

7.4 Die Röntgenstrukturanalyse entschlüsselt Proteinkonformationen

Torres J et al (2003) Membrane proteins: the 'Wild West' of structural biology, Trends

Biochem Sci 28, 137-144

Vrielink A, Sampson N (2003) Sub-Angstrom resolution enzyme X-ray structures: is

seeing believing?, Curr Opin Struct Biol 13, 709-715

Joachimiak A (2009) High-throughput crystallography for structural genomics.

Current Opinion in Structural Biology, 19, 573-584.

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7.5 Die Kernresonanzspektroskopie untersucht Proteine in Lösung

Baldwin AJ & Kay LE (2009) NMR spectroscopy brings invisible protein states into

focus. Nature Chemical Biology, 5, 808-814.

Sakurai K, Konuma T, Yagi M, & Goto Y (2009) Structural dynamics and folding of

beta-lactoglobulin probed by heteronuclear NMR. Biochimica et Biophysica Acta-

General Subjects, 1790, 527-537.

Jensen MR, Markwick PRL, Meier S, Griesinger C, Zweckstetter M, Grzesiek S,

Bernado P, & Blackledge M (2009) Quantitative Determination of the Conformational

Properties of Partially Folded and Intrinsically Disordered Proteins Using NMR

Dipolar Couplings. Structure, 17, 1169-1185.

8 Proteine als Strukturträger

8.1 Strukturproteine bilden die Matrix des Bindegewebes

Persikov AV, Ramshaw JA et al (2002) Peptide investigations of pairwise interactions

in the collagen triple-helix, J Mol Biol 316, 385-394

Brodsky B, Thiagarajan G, Madhan B, & Kar K (2008) Triple-helical peptides: An

approach to collagen conformation, stability, and self-association. Biopolymers, 89,

345-353.

Shoulders MD & Raines RT (2009) Collagen Structure and Stability. Annual Review

of Biochemistry, 78, 929-958. (PDF)

8.2 Posttranslationale Modifikationen stabilisieren die Tripelhelix

Olsen DR, Leigh SD et al (2001) Production of human type I collagen in yeast reveals

unexpected new insights into the molecular assembly of collagen trimers, J Biol

Chem 276, 24038-24043 (PDF)

Myllyharju J (2008) Prolyl 4-hydroxylases, key enzymes in the synthesis of collagens

and regulation of the response to hypoxia, and their roles as treatment targets.

Annals of Medicine, 40, 402-417.

8.3 Chemische Quervernetzung stabilisiert die Kollagenfibrillen

Kagan HM, Li W (2003) Lysyl oxidase: properties, specificity, and biological roles

inside and outside of the cell, J Cell Biochem 88, 660-672

Robins SP (2007) Biochemistry and functional significance of collagen cross-linking.

Biochemical Society Transactions, 35, 849-852.

8.4 Störungen in der Kollagenbildung führen zu schwerwiegenden Erkrankungen

Mao JR, Bristow J (2001) The Ehlers-Danlos syndrome: on beyond collagens, J Clin

Invest 107, 1063-1069 (PDF)

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Gregersen N, Bolund L, & Bross P (2005) Protein misfolding, aggregation, and

degradation in disease. Molecular Biotechnology, 31, 141-150.

8.5 Elastin verleiht dem Bindegewebe Flexibilität

Tatham AS, Shewry PR (2000) Elastomeric proteins: biological roles, structures and

mechanisms, Trends Biochem Sci 25, 567-571

MacEwan SR & Chilkoti A (2010) Elastin-Like Polypeptides: Biomedical Applications

of Tunable Biopolymers. Biopolymers, 94, 60-77.

8.6 Proteoglykane und Glykosaminoglykane verleihen Widerstandsfähigkeit gegen Kompressionskräfte

Taylor KR & Gallo RL (2006) Glycosaminoglycans and their proteoglycans: host-

associated molecular patterns for initiation and modulation of inflammation. Faseb

Journal, 20, 9-22. (PDF)

Bishop JR, Schuksz M, & Esko JD (2007) Heparan sulphate proteoglycans fine-tune

mammalian physiology. Nature, 446, 1030-1037.

8.7 Adhäsionsproteine sind wichtige Komponenten der extrazellulären Matrix

Kaspar M, Zardi L, & Neri D (2006) Fibronectin as target for tumor therapy.

International Journal of Cancer, 118, 1331-1339.

Berrier AL & Yamada KM (2007) Cell-matrix adhesion. Journal of Cellular Physiology,

213, 565-573.

Rowe RG & Weiss SJ (2008) Breaching the basement membrane: who, when and

how? Trends in Cell Biology, 18, 560-574.

9 Proteine als molekulare Motoren

9.1 Skelettmuskelfasern enthalten geordnete Bündel aus Proteinfilamenten

Granzier H & Labeit S (2002) Cardiac titin: an adjustable multi-functional spring.

Journal of Physiology-London, 541, 335-342. (PDF)

Kim J, Lowe T, & Hoppe T (2008) Protein quality control gets muscle into shape.

Trends in Cell Biology, 18, 264-272.

9.2 Dicke und dünne Filamente gleiten bei der Kontraktion aneinander vorbei

Volkmann N, Hanein D (2000) Actomyosin: law and order in motility, Curr Opin Cell

Biol 12, 26-34

Gordon AM, Homsher E, & Regnier M (2000) Regulation of contraction in striated

muscle. Physiological Reviews, 80, 853-924. (PDF)

9.3 Myosinköpfe binden und hydrolysieren ATP

Kolomeisky AB & Fisher ME (2007) Molecular motors: A theorist's perspective.

Annual Review of Physical Chemistry, 58, 675-695.

Spudich JA & Sivaramakrishnan S (2010) Myosin VI: an innovative motor that

challenged the swinging lever arm hypothesis. Nature Reviews Molecular Cell

Biology, 11, 128-137. (PDF)

9.4 Die Struktur des Myosinkopfs ist im atomaren Detail bekannt

Cooke R (1999) Myosin structure: does the tail wag the dog?, Curr Biol 9, R773-

R775

Sweeney HL & Houdusse A (2010) Myosin VI Rewrites the Rules for Myosin Motors.

Cell, 141, 573-582.

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9.5 Ein elektrischer Reiz löst die Muskelkontraktion aus

Michele DE, Metzger JM (2000) Physiological consequences of tropomyosin

mutations associated with cardiac and skeletal myopathies, J Mol Med 78, 543-553

Kobayashi T & Solaro RJ (2005) Calcium, thin filaments, and the integrative biology

of cardiac contractility. Annual Review of Physiology, 67, 39-67.

9.6 Glatte Muskulatur kontrahiert nach reversibler Phosphorylierung von Myosin

Wang CL (2001) Caldesmon and smooth-muscle regulation, Cell Biochem Biophys

35, 275-288

Murthy KS (2006) Signaling for contraction and relaxation in smooth muscle of the

gut. Annual Review of Physiology, 68, 345-374.

9.7 Die Duchenne-Muskeldystrophie beruht auf einem Defekt im Dystrophingen

Cossu G & Sampaolesi M (2007) New therapies for Duchenne muscular dystrophy:

challenges, prospects and clinical trials. Trends in Molecular Medicine, 13, 520-526.

Woolner S & Bement WM (2009) Unconventional myosins acting unconventionally.

Trends in Cell Biology, 19, 245-252.

10 Dynamik sauerstoffbindender Proteine

10.1 Myoglobin bindet Sauerstoff mittels seiner prosthetischen Gruppe

Brunori M (2001) Nitric oxide moves myogobin to center stage, Trends Biochem Sci

26, 209-210

Wittenberg JB & Wittenberg BA (2003) Myoglobin function reassessed. Journal of

Experimental Biology, 206, 2011-2020. (PDF)

10.2 Die Sauerstoffdissoziationskurve von Myoglobin ist hyperbolisch

Garry D et al (1998) Mice without myoglobin, Nature 395, 905-908

Gros G, Wittenberg BA, & Jue T (2010) Myoglobin's old and new clothes: from

molecular structure to function in living cells. Journal of Experimental Biology, 213,

2713-2725.

10.3 Hämoglobin ist ein tetrameres Protein

Kundu S et al (2003) Plants, humans and hemoglobins, Trends Plant Sci 8, 387-393

Lukin JA, Ho C (2004) The structure - function relationship of hemoglobin in solution

at atomic resolution, Chem Rev 104, 1219-1230

10.4 Die Sauerstoffbindung von Hämoglobin ist kooperativ

Manning JM et al (1999) Remote contributions to subunit interactions: lessons from

adult and fetal hemoglobins, Trends Biochem Sci 24, 211-212

Ackers GK & Holt JM (2006) Asymmetric cooperativity in a symmetric tetramer:

Human hemoglobin. Journal of Biological Chemistry, 281, 11441-11443. (PDF)

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10.5 Oxy- und Desoxyhämoglobin unterscheiden sich in ihrer Raumstruktur

Verde C, Vergara A, Mazzarella L, & di Prisco G (2008) The Hemoglobins of Fishes

Living at Polar Latitudes - Current Knowledge on Structural Adaptations in a

Changing Environment. Current Protein & Peptide Science, 9, 578-590.

Bellelli A (2010) Hemoglobin and Cooperativity: Experiments and Theories. Current

Protein & Peptide Science, 11, 2-36.

10.6 Zwei unterschiedliche Modelle beschreiben kooperatives Verhalten

Royer WE, Knapp JE, Strand K, & Heaslet HA (2001) Cooperative hemoglobins:

conserved fold, diverse quaternary assemblies and allosteric mechanisms. Trends in

Biochemical Sciences, 26, 297-304.

Shikama K (2006) Nature of the FeO2 bonding in myoglobin and hemoglobin: A new

molecular paradigm. Progress in Biophysics & Molecular Biology, 91, 83-162.

10.7 2,3-Bisphosphoglycerat bindet in der zentralen Pore des Hämoglobins

Yachie-Kinoshita A, Nishino T, Shimo H, Suematsu M, & Tomita M (2010) A

Metabolic Model of Human Erythrocytes: Practical Application of the E-Cell

Simulation Environment. Journal of Biomedicine and Biotechnology. (PDF)

10.8 Protonierung von Hämoglobin erleichtert die O2-Abgabe in den

Kapillaren

Lane P, Gross S (2002) Hemoglobin as a chariot for NO bioactivity, Nat Med 8, 657-

658

Gladwin MT et al (2003) Nitric oxide's reactions with hemoglobin: a view through the

SNO-storm, Nat Med 9, 496-500

Giardina B, Mosca D, & De Rosa MC (2004) The Bohr effect of haemoglobin in

vertebrates: an example of molecular adaptation to different physiological

requirements. Acta Physiologica Scandinavica, 182, 229-244.

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10.9 Hämoglobinopathien beruhen auf molekularen Defekten von Hämoglobin

Strasser BJ (1999) Sickle cell anemia, a molecular disease, Science 286, 1488-1490

Allison AC (2002) The discovery of resistance to malaria of sickle-cell heterozygotes,

Biochem Mol Biol Educ 30, 279-287 (PDF)

Smiley D, Dagogo-Jack S, & Umpierrez G (2008) Therapy Insight: metabolic and

endocrine disorders in sickle cell disease. Nature Clinical Practice Endocrinology &

Metabolism, 4, 102-109.

10.10 Eisen wird mithilfe von Proteinen resorbiert, transportiert und gespeichert

Aisen P et al (1999) Iron metabolism, Curr Opin Chem Biol 3, 200-206

Dunn LL, Rahmanto YS, & Richardson DR (2007) Iron uptake and metabolism in the

new millennium. Trends in Cell Biology, 17, 93-100.

Roy CN, Enns CA (2000) Iron homeostasis: new tales from the crypt, Blood 96,

4020-4027 (PDF)

11 Proteine als molekulare Katalysatoren

11.1 Enzyme haben eine hohe Substrat- und Reaktionsspezifität

Mesecar A & Koshland D (2000) A new model for protein stereospecificity, Nature

403, 614-615

Copley SD (2003) Enzymes with extra talents: moonlighting functions and catalytic

promiscuity, Curr Opin Chem Biol 7, 265-272

Siddiqui KS & Cavicchioli R (2006) Cold-adapted enzymes. Annual Review of

Biochemistry, 75, 403-433.

11.2 Das aktive Zentrum wird von reaktiven Aminosäuren gebildet

Wolfe MS, Kopan R (2004) Intramembrane proteolysis: theme and variations,

Science 305, 1119-1123

Eliot AC, Kirsch JF (2004) Pyridoxal phosphate enzymes: mechanistic, structural,

and evolutionary considerations, Annu Rev Biochem 73, 383-415

Berger F et al (2004) The new life of a centenarian: signalling functions of NAD(P),

Trends Biochem Sci 29, 111-118

Khersonsky O, Roodveldt C, & Tawfik DS (2006) Enzyme promiscuity: evolutionary

and mechanistic aspects. Current Opinion in Chemical Biology, 10, 498-508.

11.3 Enzyme werden nach Art der katalysierten Reaktion klassifiziert

Hult K & Berglund P (2007) Enzyme promiscuity: mechanism and applications.

Trends in Biotechnology, 25, 231-238.

11.4 Der Übergangszustand liegt zwischen Edukt und Produkt einer Reaktion

Warshel A, Sharma PK, Kato M, Xiang Y, Liu HB, & Olsson MHM (2006) Electrostatic

basis for enzyme catalysis. Chemical Reviews, 106, 3210-3235.

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11.5 Enzyme setzen die freie Aktivierungsenergie von Reaktionen herab

Stroppolo ME et al (2001) Superefficient enzymes, Cell Mol Life Sci 58, 1451-1460

Garcia-Viloca M et al (2004) How enzymes work: analysis by modern rate theory and

computer simulations, Science 303, 186-195

Hu H & Yang WT (2008) Free energies of chemical reactions in solution and in

enzymes with ab initio quantum mechanics/molecular mechanics methods. Annual

Review of Physical Chemistry, 59, 573-601.

12 Mechanismen der Katalyse

12.1 Enzyme nutzen unterschiedliche Katalysestrategien

Kraut DA et al (2003) Challenges in enzyme mechanism and energetics, Annu Rev

Biochem 72, 517-71

Evans MJ & Cravatt BF (2006) Mechanism-based profiling of enzyme families.

Chemical Reviews, 106, 3279-3301.

12.2 Enzyme binden bevorzugt den Übergangszustand

Borden J, Crans DC, & Florian J (2006) Transition state analogues for nucleotidyl

transfer reactions: Structure and stability of pentavalent vanadate and phosphate

ester dianions. Journal of Physical Chemistry B, 110, 14988-14999.

Senn HM & Thiel W (2007) QM/MM studies of enzymes. Current Opinion in Chemical

Biology, 11, 182-187.

Wojcik T & Kiec-Kononowicz K (2008) Catalytic activity of certain antibodies as a

potential tool for drug synthesis and for directed prodrug therapies. Current Medicinal

Chemistry, 15, 1606-1615.

12.3 Lactat-Dehydrogenase verschließt nach Substratbindung das aktive Zentrum

Gutteridge A, Thornton J (2004) Conformational change in substrate binding,

catalysis and product release: an open and shut case?, FEBS Lett 567, 67-73

Zhou SF, Zhou ZW, Yang LP, & Cai JP (2009) Substrates, Inducers, Inhibitors and

Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in

Drug Development. Current Medicinal Chemistry, 16, 3480-3675.

12.4 Die katalytische Triade ist das Herzstück im aktiven Zentrum von Trypsin

Blow D (1997) The tortuous story of Asp...His...Ser: Structural analysis of

chymotrypsin , Trends Biochem Sci 22, 405-408

20

Hedstrom L (2002) Serine protease mechanism and specificity, Chem Rev 102,

4501-4524

Ekici OD, Paetzel M, & Dalbey RE (2008) Unconventional serine proteases:

Variations on the catalytic Ser/His/Asp triad configuration. Protein Science, 17, 2023-

2037. (PDF)

12.5 Trypsin bildet eine kovalentes Acyl-Intermediat

Wilmouth R et al (2001) X-Ray snapshots of serine protease catalysis reveals a

tetrahedral intermediate, Nature Struct Biol 8, 689-694

Dunn BM & Uversky VN (2009) Cryoenzymology: Enzyme Action in Slow Motion.

Current Protein & Peptide Science, 10, 408-415.

12.6 Proteasen haben vielfältige biologische Aufgaben

De Clercq E (2007) The design of drugs for HIV and HCV. Nature Reviews Drug

Discovery, 6, 1001-1018.

Page MJ & Di Cera E (2008) Serine peptidases: Classification, structure and

function. Cellular and Molecular Life Sciences, 65, 1220-1236.

12.7 Ribozyme sind katalytisch aktive Ribonucleinsäuren

Lilley DM (2003) The origins of RNA catalysis in ribozymes, Trends Biochem Sci 28,

495-501

Isaacs FJ, Dwyer DJ, & Collins JJ (2006) RNA synthetic biology. Nature

Biotechnology, 24, 545-554.

Serganov A & Patel DJ (2007) Ribozymes, riboswitches and beyond: regulation of

gene expression without proteins. Nature Reviews Genetics, 8, 776-790.

21

13 Regulation der Enzymaktivität

13.1 Geschwindigkeitskonstanten charakterisieren chemische Reaktionen

Kraut DA, Carroll KS, & Herschlag D (2003) Challenges in enzyme mechanism and

energetics. Annual Review of Biochemistry, 72, 517-571.

Walde S & Kehlenbach RH (2010) The Part and the Whole: functions of nucleoporins

in nucleocytoplasmic transport. Trends in Cell Biology, 20, 461-469.

13.2 Die Michaelis-Menten-Gleichung beschreibt eine einfache Enzymkinetik

Xie XS, Lu HP (1999) Single-molecule enzymology, J Biol Chem 274, 15967-70

(PDF)

Atkins WM (2005) Non-Michaelis-Menten kinetics in cytochrome P450-catalyzed

reactions. Annual Review of Pharmacology and Toxicology, 45, 291-310.

Moffitt JR, Chemla YR, & Bustamante C (2010) Methods in Statistical Kinetics.

Elsevier Academic Press Inc., San Diego.

13.3 Michaelis-Konstante und Wechselzahl sind wichtige Kenngrößen von Enzymen

Fox RJ & Clay MD (2009) Catalytic effectiveness, a measure of enzyme proficiency

for industrial applications. Trends in Biotechnology, 27, 137-140.

13.4 Die Enzymkinetik hilft bei der Untersuchung von Enzymmechanismen

Peracchi A (2001) Enzyme catalysis: removing chemically 'essential' residues by site-

directed mutagenesis, Trends Biochem Sci 26, 497-503

Cleland WW (2005) The use of isotope effects to determine enzyme mechanisms.

Archives of Biochemistry and Biophysics, 433, 2-12.

22

13.5 Kompetitive Inhibitoren binden an das aktive Zentrum und verhindern den Substratzutritt

Istvan ES, Deisenhofer J (2001) Structural mechanism for statin inhibition of HMG-

CoA reductase, Science 292, 1160-1164

Simmons DL et al (2004) Cyclooxygenase isozymes: the biology of prostaglandin

synthesis and inhibition, Pharmacol Rev 56, 387-437

Tafi A, Angeli L, Venturini G, Travagli M, Corelli F, & Botta M (2006) Computational

studies of competitive inhibitors of nitric oxide synthase (NOS) enzymes: Towards the

development of powerful and isoform selective inhibitors. Current Medicinal

Chemistry, 13, 1929-1946.

13.6 Hohe Substratkonzentrationen heben die kompetitive Inhibition auf

Schep LJ, Slaughter RJ, Temple WA, & Beasley DMG (2009) Diethylene glycol

poisoning. Clinical Toxicology, 47, 525-535.

13.7 Kovalent bindende Inhibitoren hemmen irreversibel

Nitiss JL (2009) Targeting DNA topoisomerase II in cancer chemotherapy. Nature

Reviews Cancer, 9, 338-350. (PDF)

Singh J, Petter RC, & Kluge AF (2010) Targeted covalent drugs of the kinase family.

Current Opinion in Chemical Biology, 14, 475-480.

13.8 Allosterische Regulatoren modulieren die Enzymaktivität

Dijkstra BW, Matthews RG (2003) Catalysis and regulation - from structure to

function, Curr Opin Struct Biol 13, 706-708

Goodey NM & Benkovic SJ (2008) Allosteric regulation and catalysis emerge via a

common route. Nature Chemical Biology, 4, 474-482.

13.9 Heterotrope Effektoren binden an regulatorische Untereinheiten

Lim WA (2002) The modular logic of signaling proteins: building allosteric switches

from simple binding domains, Curr Opin Struct Biol 12, 61-68

23

24

Villaverde A (2003) Allosteric enzymes as biosensors for molecular diagnosis, FEBS

Lett 554, 169-172

Gold MG, Barford D, & Komander D (2006) Lining the pockets of kinases and

phosphatases. Current Opinion in Structural Biology, 16, 693-701.

13.10 Reversible Phosphorylierung reguliert die Enzymaktivität

Kolmodin K, Aqvist J (2001) The catalytic mechanism of protein tyrosine

phosphatases revisited, FEBS Lett 498, 208-213

Hirose Y & Ohkuma Y (2007) Phosphorylation of the c-terminal domain of RNA

polymerase II plays central roles in the integrated events of eucaryotic gene

expression. Journal of Biochemistry, 141, 601-608.

Pulido R & Hooft van Huijsduijnen R (2008) Protein tyrosine phosphatases: dual-

specificity phosphatases in health and disease. Febs Journal, 275, 848-866.

13.11 Gezielte proteolytische Spaltungen können Zymogene aktivieren

Krem MM, Di Cera E (2002) Evolution of enzyme cascades from embryonic

development to blood coagulation, Trends Biochem Sci 27, 67-74

Amour A et al (2004) General considerations for proteolytic cascades, Biochem Soc

Trans 32, 15-16

Pop C & Salvesen GS (2009) Human Caspases: Activation, Specificity, and

Regulation. Journal of Biological Chemistry, 284, 21777-21781. (PDF)

14 Enzymkaskaden des Bluts

14.1 Proteolytische Kaskaden steuern die Bildung und Auflösung von Blutgerinnseln

Davidson CJ et al (2003) 450 million years of hemostasis, J Thromb Haemost 1,

1487-1494

Schenone M et al (2004) The blood coagulation cascade, Curr Opin Hematol 11,

272-277

Monroe DM & Hoffman M (2006) What does it take to make the perfect clot?

Arteriosclerosis Thrombosis and Vascular Biology, 26, 41-48. (PDF)

14.2 Die Initiation der Gerinnungskaskade erfolgt über den Gewebsfaktor

McVey JH (2003) Your bleeding heart: lessons from low tissue factor expression in

mice, Trends Pharmacol Sci 24, 269-272

Hoffman M (2003) A cell-based model of coagulation and the role of factor VIIa,

Blood Rev 17, S1-5

Mann KG, Kalafatis M (2003) Factor V: a combination of Dr Jekyll and Mr Hyde,

Blood 101, 20-30 (PDF)

Persson E, Bolt G, Steenstrup TD, & Ezban M (2010) Recombinant coagulation

factor VIIa - from molecular to clinical aspects of a versatile haemostatic agent.

Thrombosis Research, 125, 483-489.

14.3 Fibrinmonomere assoziieren zu einem Netzwerk

Yang Z, Mochalkin I et al (2000) Crystal structure of native chicken fibrinogen at 5.5-

A resolution, Proc Natl Acad Sci U S A 97, 3907-3912 (PDF)

Doolittle RF (2003) Structural basis of the fibrinogen-fibrin transformation:

contributions from X-ray crystallography, Blood Rev 17, 33-41

Guthold M, Liu W, Sparks EA, Jawerth LM, Peng L, Falvo M, Superfine R, Hantgan

RR, & Lord ST (2007) A comparison of the mechanical and structural properties of

fibrin fibers with other protein fibers. Cell Biochemistry and Biophysics, 49, 165-181.

25

14.4 Gerinnungsfaktoren besitzen einen modularen Aufbau

Furie B et al (1999) Vitamin K-dependent biosynthesis of gamma-carboxyglutamic

acid, Blood 93, 1798-1808 (PDF)

Lee CJ, Chandrasekaran V, Wu SW, Duke RE, & Pedersen LG (2010) Recent

Estimates of the Structure of the Factor VIIa (FVIIa)/Tissue Factor (TF) and Factor

Xa (FXa) Ternary Complex. Thrombosis Research, 125, S7-S10.

14.5 Inhibition und Proteolyse kontrollieren die Blutgerinnung

Huntington JA, Baglin TP (2003) Targeting thrombin - rational drug design from

natural mechanisms, Trends Pharmacol Sci 24, 589-595

Bussey H, Francis JL (2004) Heparin overview and issues, Pharmacotherapy 24,

103S-107S

Lwaleed BA & Bass PS (2006) Tissue factor pathway inhibitor: structure, biology and

involvement in disease. Journal of Pathology, 208, 327-339.

14.6 Das fibrinolytische System löst Thromben auf

Medved L, Nieuwenhuizen W (2003) Molecular mechanisms of initiation of fibrinolysis

by fibrin, Thromb Haemost 89, 409-419

Laurens N, Koolwijk P, & De Maat MPM (2006) Fibrin structure and wound healing.

Journal of Thrombosis and Haemostasis, 4, 932-939.

Zorio E, Gilabert-Estelles J, Espana F, Ramon LA, Cosin R, & Estelles A (2008)

Fibrinolysis: The key to new pathogenetic mechanisms. Current Medicinal Chemistry,

15, 923-929.

14.7 Defekte Gerinnungsfaktoren führen zur Hämophilie

Bolton-Maggs PH, Pasi KJ (2003) Haemophilias A and B, Lancet 361, 1801-1809

Nathwani AC et al (2004) Prospects for gene therapy of haemophilia, Haemophilia

10, 309-318

O'Connor TP & Crystal RG (2006) Genetic medicines: treatment strategies for

hereditary disorders. Nature Reviews Genetics, 7, 261-276.

26

27

Nichols WL, Hultin MB, James AH, Manco-Johnson MJ, Montgomery RR, Ortel TL,

Rick ME, Sadler JE, Weinstein M, & Yawn BP (2008) von Willebrand disease (VWD):

evidence-based diagnosis and management guidelines, the National Heart, Lung,

and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia, 14, 171-232.

15 Evolution der Proteine

15.1 Mutationen und Duplikationen treiben die Proteinevolution an

Kinch LN, Grishin NV (2002) Evolution of protein structures and functions, Curr Opin

Struct Biol 12, 400-408

Kondrashov FA & Kondrashov AS (2006) Role of selection in fixation of gene

duplications. Journal of Theoretical Biology, 239, 141-151.

Conant GC & Wolfe KH (2008) Turning a hobby into a job: How duplicated genes find

new functions. Nature Reviews Genetics, 9, 938-950.

Soskine M & Tawfik DS (2010) Mutational effects and the evolution of new protein

functions. Nature Reviews Genetics, 11, 572-582.

15.2 Domänen sind die Bausteine der Proteinevolution

Khosla C, Harbury PB (2001) Modular enzymes, Nature 409, 247-252

Kolkman JA, Stemmer WP (2001) Directed evolution of proteins by exon shuffling,

Nat Biotechnol 19, 423-428

Bhattacharyya RP, Remenyi A, Yeh BJ, & Lim WA (2006) Domains, motifs, and

scaffolds: The role of modular interactions in the evolution and wiring of cell signaling

circuits. Annual Review of Biochemistry, 75, 655-680.

Han JH, Batey S, Nickson AA, Teichmann SA, & Clarke J (2007) The folding and

evolution of multidomain proteins. Nature Reviews Molecular Cell Biology, 8, 319-

330.

15.3 Sequenzvergleiche spüren Schlüsselpositionen in verwandten Proteinen auf

Jeanmougin F et al (1998) Multiple sequence alignment with Clustal X, Trends

Biochem Sci 23, 403-405

Kumar S & Filipski A (2007) Multiple sequence alignment: In pursuit of homologous

DNA positions. Genome Research, 17, 127-135. (PDF)

Lenaerts T, Schymkowitz J, & Rousseau F (2009) Protein Domains as Information

Processing Units. Current Protein & Peptide Science, 10, 133-145.

28

15.4 Der Vergleich von Tertiärstrukturen verrät entfernte Verwandtschaften

Hocker B et al (2002) A common evolutionary origin of two elementary enzyme folds,

FEBS Lett 510, 133-135

Lee D et al (2003) A structural perspective on genome evolution, Curr Opin Struct

Biol 13, 359-369

Carugo O (2007) Recent progress in measuring structural similarity between

proteins. Current Protein & Peptide Science, 8, 219-241.

15.5 Proteine werden in Datenbanken gesammelt

Orengo CA et al (2001) Review: what can structural classifications reveal about

protein evolution?, J Struct Biol 134, 145-165

Koonin EV et al (2002) The structure of the protein universe and genome evolution,

Nature 420, 218-223

Shen MY & Sali A (2006) Statistical potential for assessment and prediction of protein

structures. Protein Science, 15, 2507-2524. (PDF)

Dunbrack RL (2006) Sequence comparison and protein structure prediction. Current

Opinion in Structural Biology, 16, 374-384.

Raman P, Cherezov V, & Caffrey M (2006) The membrane protein data bank.

Cellular and Molecular Life Sciences, 63, 36-51. (PDF)

15.6 Die Zahl der Proteine ist sehr viel größer als die der Gene

Burley SK, Bonanno JB (2002) Structural genomics of proteins from conserved

biochemical pathways and processes, Curr Opin Struct Biol 12, 383-391

Blencowe BJ (2006) Alternative splicing: New insights from global analyses. Cell,

126, 37-47.

Jensen ON (2006) Interpreting the protein language using proteomics. Nature

Reviews Molecular Cell Biology, 7, 391-403.

29

Teil III Speicherung und Ausprägung von Erbinformation

16 Nucleinsäuren – Struktur und Organisation

16.1 Aufbau der DNA

Burge S, Parkinson GN, Hazel P, Todd AK, & Neidle S (2006) Quadruplex DNA:

sequence, topology and structure. Nucleic Acids Research, 34, 5402-5415. (PDF)

16.2 Antiparallele DNA-Stränge bilden eine Doppelhelix

Watson JD, Crick FHC (1953) Molecular structure of nucleic acids, Nature 171, 737-

738 (PDF)

Andersen ES (2010) Prediction and design of DNA and RNA structures. New

Biotechnology, 27, 184-193.

16.3 Die Asymmetrie der Basenpaare erzeugt kleine und große Furchen

Dickerson RE et al (1982) The anatomy of A-, B- and Z-DNA, Science 216, 475-485

Herbert A, Rich A (1996) The biology of lefthanded Z-DNA, J Biol Chem 271, 11595-

598 (PDF)

Mooers BH (2009) Crystallographic studies of DNA and RNA. Methods, 47, 168-176.

Masquida B, Beckert B, & Jossinet F (2010) Exploring RNA structure by integrative

molecular modelling. New Biotechnology, 27, 170-183.

16.4 Chromosomen sind Komplexe aus DNA und Histonen

Luger K et al (1997) Crystal structure of the nucleosome core particle at 2.8 Å

resolution, Nature 389, 251-260

Shilatifard A (2006) Chromatin modifications by methylation and ubiquitination:

Implications in the regulation of gene expression. Annual Review of Biochemistry, 75,

243-269.

30

31

Li B, Carey M, & Workman JL (2007) The role of chromatin during transcription. Cell,

128, 707-719.

Taverna SD, Li H, Ruthenburg AJ, Allis CD, & Patel DJ (2007) How chromatin-

binding modules interpret histone modifications: lessons from professional pocket

pickers. Nature Structural & Molecular Biology, 14, 1025-1040.

16.5 Nucleosomen bilden die Glieder einer Chromatinkette

Hirano T (2006) At the heart of the chromosome: SMC proteins in action. Nature

Reviews Molecular Cell Biology, 7, 311-322.

Bailey SM & Murnane JP (2006) Telomeres, chromosome instability and cancer.

Nucleic Acids Research, 34, 2408-2417. (PDF)

Bazile F, St-Pierre J, & D'Amours D (2010) Three-step model for condensin

activation during mitotic chromosome condensation. Cell Cycle, 9, 3243-3255.

(Website)

16.6 Das Genom von E. coli ist ringförmig

Blattner FR et al (1997) The complete genome sequence of Escherichia coli K-12,

Science 277, 1453-62

Espeli O & Boccard F (2006) Organization of the Escherichia coli chromosome into

macrodomains and its possible functional implications. Journal of Structural Biology,

156, 304-310.

17 Transkription – Umschrift genetischer Information

17.1 Ribonucleinsäuren sind Produkte der Transkription

Orphanides G, Reinberg D (2002) A unified theory of gene expression, Cell 108, 439-

451

White RJ & Sharrocks AD (2010) Coordinated control of the gene expression

machinery. Trends in Genetics, 26, 214-220.

17.2 Die Transkription startet an der Promotorregion

Hahn S (2004) Structure and mechanism of the RNA polymerase II transcription

machinery, Nat Struct Mol Biol 11, 394-403 (PDF)

Haugen SP, Ross W, & Gourse RL (2008) Advances in bacterial promoter

recognition and its control by factors that do not bind DNA. Nature Reviews

Microbiology, 6, 507-519.

17.3 RNA-Polymerase windet den Doppelstrang auf

Woychik NA, Hampsey M (2002) The RNA polymerase II machinery: structure,

illuminates function, Cell 108, 453-463

Kornberg RD (2007) The molecular basis of eucaryotic transcription. Cell Death and

Differentiation, 14, 1989-1997. (PDF)

17.4 Eukaroytische Zellen besitzen drei nucleäre RNA-Polymerasen

Cramer P, Armache KJ, Baumli S, Benkert S, Brueckner E, Buchen C, Damsma GE,

Dengl S, Geiger SR, Jaslak AJ, Jawhari A, Jennebach S, Kamenski T, Kettenberger

H, Kuhn CD, Lehmann E, Leike K, Sydow JE, & Vannini A (2008) Structure of

eukaryotic RNA polymerases. Annual Review of Biophysics, 37, 337-352.

Geiduschek EP (2009) Without a License, or Accidents Waiting to Happen. Annual

Review of Biochemistry, 78, 1-28.

Selth LA, Sigurdsson S, & Svejstrup JQ (2010) Transcript Elongation by RNA

Polymerase II. ANNUAL REVIEWS, PALO ALTO.

32

17.5 Eukaryotische RNA macht eine Reifung durch

Proudfoot NJ et al (2002) Integrating mRNA processing with transcription, Cell 108,

501-512

Shyu AB, Wilkinson MF, & van Hoof A (2008) Messenger RNA regulation: to

translate or to degrade. Embo Journal, 27, 471-481. (PDF)

17.6 Der Spleißvorgang entfernt Introns aus unreifer RNA

Roy SW & Gilbert W (2006) The evolution of spliceosomal introns: patterns, puzzles

and progress. Nature Reviews Genetics, 7, 211-221.

Wang GS & Cooper TA (2007) Splicing in disease: disruption of the splicing code and

the decoding machinery. Nature Reviews Genetics, 8, 749-761.

Wang GS & Cooper TA (2007) Splicing in disease: disruption of the splicing code and

the decoding machinery. Nature Reviews Genetics, 8, 749-761.

17.7 Das Spleißosom ist ein multikatalytischer Komplex

Murray HL, Jarrell KA (1999) Flipping the switch to an active spliceosome, Cell 96,

599-602

Stahley MR & Strobel SA (2006) RNA splicing: group I intron crystal structures reveal

the basis of splice site selection and metal ion catalysis. Current Opinion in Structural

Biology, 16, 319-326.

17.8 Alternatives Spleißen und RNA-Editing erhöhen die strukturelle Variabilität

Gott JM, Emeson RB (2000) Functions and mechanisms of RNA editing, Annu Rev

Genet 34, 499-531

Blencowe BJ (2006) Alternative splicing: New insights from global analyses. Cell,

126, 37-47.

Xing Y & Lee C (2006) Alternative splicing and RNA selection pressure - evolutionary

consequences for eukaryotic genomes. Nature Reviews Genetics, 7, 499-509.

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34

17.9 RNA-Polymerase I produziert ribosomale RNA

Scheer U, Hock R (1999) Structure and function of the nucleolus, Curr Opin Cell Biol

11, 385-390

Haeusler RA & Engelke DR (2006) Spatial organization of transcription by RNA

polymerase III. Nucleic Acids Research, 34, 4826-4836. (PDF)

Boisvert FM, van Koningsbruggen S, Navascues J, & Lamond AI (2007) The

multifunctional nucleolus. Nature Reviews Molecular Cell Biology, 8, 574-585.

17.10 Transfer-RNAs werden posttranskriptional modifiziert

Kirsebohm LA (2002) RNase P RNA-mediated catalysis, Biochem Soc Trans 30,

1153-58

Kazantsev AV & Pace NR (2006) Bacterial RNase P: a new view of an ancient

enzyme. Nature Reviews Microbiology, 4, 729-740.

Agris PF, Vendeix FAP, & Graham WD (2007) tRNA's wobble decoding of the

genome: 40 years of modification. Journal of Molecular Biology, 366, 1-13.

Gustilo EM, Franck APF, & Agris PF (2008) tRNA's modifications bring order to gene

expression. Current Opinion in Microbiology, 11, 134-140. (PDF)

18 Translation – Decodierung genetischer Information

18.1 Basentripletts sind genetische Informationseinheiten

Kapp LD, Lorsch JR (2004) The Molecular Mechanisms of Eucarytic Translation,

Annu Rev Biochem 73, 657-704

Koonin EV & Novozhilov AS (2009) Origin and Evolution of the Genetic Code: The

Universal Enigma. Iubmb Life, 61, 99-111.

18.2 Transfer-Ribonucleinsäuren haben eine bipolare Struktur

Ogle JM et al (2003) Insights into the decoding mechanism from recent ribosome

structures, Trends Biochem Sci 28, 259-265

Park SG, Schimmel P, & Kim S (2008) Aminoacyl tRNA synthetases and their

connections to disease. Proceedings of the National Academy of Sciences of the

United States of America, 105, 11043-11049. (PDF)

Guo M, Yang XL, & Schimmel P (2010) New functions of aminoacyl-tRNA

synthetases beyond translation. Nature Reviews Molecular Cell Biology, 11, 668-674.

18.3 Ribosomen dienen bei der Translation als Werkbänke

Yusupov M et al (2001) Crystal structure of the ribosome at 5.5 Å resolution, Science

292, 883-896

Beringer M & Rodnina MV (2007) The ribosomal peptidyl transferase. Molecular Cell,

26, 311-321.

Steitz TA (2008) A structural understanding of the dynamic ribosome machine.

Nature Reviews Molecular Cell Biology, 9, 242-253.

Schmeing TM & Ramakrishnan V (2009) What recent ribosome structures have

revealed about the mechanism of translation. Nature, 461, 1234-1242.

18.4 Initiationsfaktoren steuern die Startphase der Translation

Proud CG (2007) Signalling to translation: how signal transduction pathways control

the protein synthetic machinery. Biochemical Journal, 403, 217-234.

35

Hinnebusch AG (2006) eIF3: a versatile scaffold for translation initiation complexes.

Trends in Biochemical Sciences, 31, 553-562.

Kolitz SE & Lorsch JR (2010) Eukaryotic initiator tRNA: Finely tuned and ready for

action. Febs Letters, 584, 396-404.

18.5 Molekulare Roboter assemblieren die Polypeptidkette

Crick FHC (1966) Codon-anticodon pairing: the wobble hypothesis, J Mol Biol 19,

548-555

Andersen GR, et al (2003) Elongation factors in protein biosynthesis, Trends

Biochem Sci 28, 434-441

Abbott CM, Proud CG (2004) Translation factors, in sickness and in health, Trends

Biochem Sci 29, 25-31

Peterlin BM & Price DH (2006) Controlling the elongation phase of transcription with

P-TEFb. Molecular Cell, 23, 297-305.

Mateyak MK & Kinzy TG (2010) eEF1A: Thinking Outside the Ribosome. Journal of

Biological Chemistry, 285, 21209-21213.

18.6 Die Proteinbiosynthese ist ein ökonomischer Prozess

Rodnina MV, Wintermeyer W (2001) Ribosome fidelity, tRNA discrimination,

proofreading and induced fit, Trends Biochem Sci 26, 124-130

Zaher HS & Green R (2009) Fidelity at the Molecular Level: Lessons from Protein

Synthesis. Cell, 136, 746-762.

18.7 Die Translation wird effizient kontrolliert

Kimball SR (1999) Eukaryotic initiation factor eIF2, Int J Biochem Cell Biol 31, 25-29

Browne GJ, Proud CG (2002) Regulation of peptide-chain elongation in mammalian

cells, Eur J Biochem 269, 5360-68

Munro JB, Sanbonmatsu KY, Spahn CMT, & Blanchard SC (2009) Navigating the

ribosome's metastable energy landscape. Trends in Biochemical Sciences, 34, 390-

400. (PDF)

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37

18.8 Viele Antibiotika sind Hemmer der Translation

Gaynor M, Mankin AS (2003) Macrolide antibiotics: binding site, mechanism of

action, resistance, Curr Top Med Chem 3, 949-961

Ippolito JA, Kanyo ZF, Wang DP, Franceschi FJ, Moore PB, Steitz TA, & Duffy EM

(2008) Crystal structure of the oxazolidinone antibiotic linezolid bound to the 50S

ribosomal subunit. Journal of Medicinal Chemistry, 51, 3353-3356.

19 Posttranslationale Prozessierung und Sortierung von Proteinen

19.1 Zellen sortieren Proteine nach der Translation

Saibil HR, Ranson N (2002) The chaperonin folding machine, Trends Biochem Sci

27, 627-632

Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent

chain to folded protein, Science 295, 1852-1858

Appenzeller-Herzog C & Hauri HP (2006) The ER-Golgi intermediate compartment

(ERGIC): in search of its identity and function. Journal of Cell Science, 119, 2173-

2183. (PDF)

Saibil HR (2008) Chaperone machines in action. Current Opinion in Structural

Biology, 18, 35-42.

Mayer MP (2010) Gymnastics of Molecular Chaperones. Molecular Cell, 39, 321-331.

19.2 Signalsequenzen dirigieren Proteine zu Mitochondrien

Neupert W & Herrmann JM (2007) Translocation of proteins into mitochondria.

Annual Review of Biochemistry, 76, 723-749.

Schmidt O, Pfanner N, & Meisinger C (2010) Mitochondrial protein import: from

proteomics to functional mechanisms. Nature Reviews Molecular Cell Biology, 11,

655-667.

19.3 Nucleäre Proteine tragen Kernlokalisationssequenzen

Fahrenkrog B et al (2004) The nuclear pore complex, a jack of all trades ?, Trends

Biochem Sci 29, 174-182

Tran EJ & Wente SR (2006) Dynamic nuclear pore complexes: Life on the edge. Cell,

125, 1041-1053.

Stewart M (2007) Molecular mechanism of the nuclear protein import cycle. Nature

Reviews Molecular Cell Biology, 8, 195-208.

Walde S & Kehlenbach RH (2010) The Part and the Whole: functions of nucleoporins

in nucleocytoplasmic transport. Trends in Cell Biology, 20, 461-469.

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19.4 Signalsequenzen lotsen Ribosomen zum endoplasmatischen Reticulum

Doudna JA, Batey RT (2004) Strucural Insights into the Signal Recognition Particle,

Annu Rev Biochem 73, 539-57

Rapoport TA (2007) Protein translocation across the eukaryotic endoplasmic

reticulum and bacterial plasma membranes. Nature, 450, 663-669.

Kraut-Cohen J & Gerst JE (2010) Addressing mRNAs to the ER: cis sequences act

up! Trends in Biochemical Sciences, 35, 459-469.

19.5 Transfersequenzen regulieren den Proteineinbau in Membranen

Hessa T, Meindl-Beinker NM, Bernsel A, Kim H, Sato Y, Lerch-Bader M, Nilsson I,

White SH, & von Heijne G (2007) Molecular code for transmembrane-helix

recognition by the Sec61 translocon. Nature, 450, 1026-10U2.

White SH & von Heijne G (2008) How translocons select transmembrane helices.

Annual Review of Biophysics, 37, 23-42.

19.6 Posttranslationale Modifikationen verleihen Proteinen neue Funktionen

Kleizen B, Braakman I (2004) Protein folding and quality control in the endoplasmic

reticulum, Curr Opin Cell Biol 16, 343-349

Ni M & Lee AS (2007) ER chaperones in mammalian development and human

diseases. Febs Letters, 581, 3641-3651. (PDF)

Orlean P & Menon AK (2007) GPI anchoring of protein in yeast and mammalian cells,

or: how we learned to stop worrying and love glycophospholipids. Journal of Lipid

Research, 48, 993-1011. (PDF)

19.7 Lysosomale Proteine erhalten ein Sortierungssignal

Barr FA (2002) The golgi apparatus: going round in circles ?, Trends Cell Biol 12,

101-104

Bonifacino JS, Traub LM (2003) Signals for Sorting of Transmembrane Proteins to

Endosomes and Lysosomes, Annu Rev Biochem 72, 395-447

39

Zhang M, Chen L, Wang SC, & Wang TL (2009) Rab7: roles in membrane trafficking

and disease. Bioscience Reports, 29, 193-209.

19.8 Terminale Glykosylierungen laufen im medialen Golgi ab

Ohtsubo K & Marth JD (2006) Glycosylation in cellular mechanisms of health and

disease. Cell, 126, 855-867.

Molinari M (2007) N-glycan structure dictates extension of protein folding or onset of

disposal. Nature Chemical Biology, 3, 313-320.

19.9 Vesikulärer Transport ist spezifisch und gerichtet

Bonifacino JS, Traub LM (2003) Signals for Sorting of Transmembrane Proteins to

Endosomes and Lysosomes, Annu Rev Biochem 72, 395-447

Edeling MA, Smith C, & Owen D (2006) Life of a clathrin coat: insights from clathrin

and AP structures. Nature Reviews Molecular Cell Biology, 7, 32-44.

McNiven MA (2006) Big gulps: specialized membrane domains for rapid receptor-

mediated endocytosis. Trends in Cell Biology, 16, 487-492.

19.10 Kleine G-Proteine regeln den vesikulären Transport

Haucke V (2003) Vesicle budding: a coat for the COPs, Trends Cell Biol 13, 59-60

Nie Z et al (2003) ARF and its many interactors, Curr Opin Cell Biol 15, 396-404

Dong M, Yeh F, Tepp WH, Dean C, Johnson EA, Janz R, & Chapman ER (2006)

SV2 is the protein receptor for botulinum neurotoxin A. Science, 312, 592-596.

Hsu VW, Lee SY, & Yang JS (2009) The evolving understanding of COPI vesicle

formation. Nature Reviews Molecular Cell Biology, 10, 360-364.

Beck R, Ravet M, Wieland FT, & Cassel D (2009) The COPI system: Molecular

mechanisms and function. Febs Letters, 583, 2701-2709.

19.11 Ubiquitin reguliert den Abbau cytosolischer Proteine

Glickman MH, Ciechanover A (2002) The ubiquitin-proteasome proteolytic pathway:

destruction for the sake of construction, Physiol Rev 82, 373-428

40

41

Hartmann-Petersen R et al (2003) Transferring substrates to the 26S proteasome,

Trends Biochem Sci 28, 26-31

Nandi D, Tahiliani P, Kumar A, & Chandu D (2006) The ubiquitin-proteasome system.

Journal of Biosciences, 31, 137-155. (PDF)

Mogk A, Schmidt R, & Bukau B (2007) The N-end rule pathway for regulated

proteolysis: prokaryotic and eukaryotic strategies. Trends in Cell Biology, 17, 165-

172.

20 Kontrolle der Genexpression

20.1 Ein Komplex aus allgemeinen Transkriptionsfaktoren platziert die RNA-Polymerase

Davidson I (2003) The genetics of TBP and TBP-related factors, Trends Biochem Sci

28, 391-398

Sandelin A, Carninci P, Lenhard B, Ponjavic J, Hayashizaki Y, & Hume DA (2007)

Mammalian RNA polymerase II core promoters: insights from genome-wide studies.

Nature Reviews Genetics, 8, 424-436.

Torres-Padilla ME & Tora L (2007) TBP homologues in embryo transcription: who

does what? Embo Reports, 8, 1016-1018. (PDF)

Baumann M, Pontiller J, & Ernst W (2010) Structure and Basal Transcription

Complex of RNA Polymerase II Core Promoters in the Mammalian Genome: An

Overview. Molecular Biotechnology, 45, 241-247.

20.2 Spezifische Transkriptionsfaktoren binden an definierte DNA-Segmente

Struhl K (1989) Helix-turn-helix, zinc-finger, and leucine-zipper motifs for eucaryotic

transcriptional regulatory proteins, Trends Biochem Sci 14, 137-140

Laniel MA et al (2001) Electrophoretic mobility shift assays for the analysis of DNA-

protein interactions, Methods Mol Biol 148, 13-30

Laity JH et al (2001) Zinc finger proteins: new insights into structural and functional

diversity, Curr Opin Struct Biol 11, 39-46

Wasserman WW & Sandelin A (2004) Applied bioinformatics for the identification of

regulatory elements. Nature Reviews Genetics, 5, 276-287.

20.3 HTH-Proteine binden an palindromische Sequenzen

Martinez P, Amemiya CT (2002) Genomics of the HOX gene cluster, Comp Biochem

Physiol B Biochem Mol Biol 133, 571-580

Hombria JC, Lovegrove B (2003) Beyond homeosis–HOX function in morphogenesis

and organogenesis, Differentiation 71, 461-76

42

Lemons D & McGinnis W (2006) Genomic evolution of Hox gene clusters. Science,

313, 1918-1922.

20.4 Hormonrezeptoren gehören zur Klasse der Zinkfingerproteine

Li L et al (2004) Gene regulation by SP1 and SP3, Biochem Cell Biol 82, 460-471

Novac N, Heinzel T (2004) Nuclear receptors: overview and classification,

Curr Drug Targets Inflamm Allergy 3, 335-46

Gamsjaeger R, Liew CK, Loughlin FE, Crossley M, & Mackay JP (2007) Sticky

fingers: zinc-fingers as protein-recognition motifs. Trends in Biochemical Sciences,

32, 63-70.

Siu YT & Jin DY (2007) CREB - a real culprit in oncogenesis. Febs Journal, 274,

3224-3232.

20.5 Enhancer und Silencer sitzen weitab vom Promoter

Dhillon N, Kamakaka RT (2002) Breaking through to the other side: silencers and

barriers, Curr Opin Genet Dev 12, 188-192

Cao A, Moi P (2002) Regulation of the globin genes, Pediatr Res 51, 415-21

Valenzuela L & Kamakaka RT (2006) Chromatin insulators. Annual Review of

Genetics, 40, 107-138.

Bushey AM, Dorman ER, & Corces VG (2008) Chromatin Insulators: Regulatory

Mechanisms and Epigenetic Inheritance. Molecular Cell, 32, 1-9. (PDF)

20.6 Posttranslationale Modifikationen steuern die Funktion von Transkriptionsfaktoren

Benayoun BA & Veitia RA (2009) A post-translational modification code for

transcription factors: sorting through a sea of signals. Trends in Cell Biology, 19, 189-

197.

43

44

20.7 Chemische Modifikation von Histonen reguliert die Expression von Genen

Carrozza MJ et al (2003) The diverse functions of histone acetyltransferase

complexes, Trends Genet 19, 321-9

Peterson CL, Laniel MA (2004) Histones and histone modifications, Curr Biol 27,

R546-51

Lee KK & Workman JL (2007) Histone acetyltransferase complexes: one size doesn't

fit all. Nature Reviews Molecular Cell Biology, 8, 284-295.

Li B, Carey M, & Workman JL (2007) The role of chromatin during transcription. Cell,

128, 707-719.

Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification

maps. Nature Reviews Genetics, 8, 286-298.

20.8 Die Methylierung von CG-reichen Regionen inaktiviert Gene

Wilkins JF, Haig D (2003) What good is genomic imprinting: the function of parent-

specific gene expression, Nature Rev Gen 4, 1-10

Hermann A et al (2004) Biochemistry and biology of mammalian DNA

methyltransferases, Cell Mol Life Sci 61, 2571-87.

Klose RJ & Bird AP (2006) Genomic DNA methylation: the mark and its mediators.

Trends in Biochemical Sciences, 31, 89-97.

Suzuki MM & Bird A (2008) DNA methylation landscapes: provocative insights from

epigenomics. Nature Reviews Genetics, 9, 465-476.

21 Replikation – Kopieren genetischer Information

21.1 Die DNA-Replikation ist semikonservativ

Davey MJ, O´Donnell M (2000) Mechanisms of DNA replication, Curr Opin Chem Biol

4, 581-586

Bell SP, Dutta A (2002) DNA Replication in Eucaryotic Cells, Annu Rev Biochem 71,

333-74

Masai H, Matsumoto S, You ZY, Yoshizawa-Sugata N, & Oda M (2010) Eukaryotic

Chromosome DNA Replication: Where, When and How? ANNUAL REVIEWS, PALO

ALTO.

21.2 Origin-bindende Proteine eröffnen die Replikation

Gilbert DM (2001) Making sense of eukaryotic DNA replication origins, Science 294,

96-100 (PDF)

Soultanas P, Wigley DB (2001) Unwinding the ´Gordian knot´ of helicase action,

Trends Biochem Sci 26, 47-54

Mott ML & Berger JM (2007) DNA replication initiation: mechanisms and regulation in

bacteria. Nature Reviews Microbiology, 5, 343-354.

Singleton MR, Dillingham MS, & Wigley DB (2007) Structure and mechanism of

helicases and nucleic acid translocases. Annual Review of Biochemistry, 76, 23-50.

21.3 Die Synthese des Folgestrangs läuft über mehrere Stufen

Frick DN, Richardson CC (2001) DNA primases, Annu Rev Biochem 70, 39-80

O´Donnell M et al (2001) Clamp loader structure predicts the architecture of DNA

polymerase III holoenzyme and RFC, Curr Biol 11, R935-R946

Hübscher U et al (2002) Eukaryotic DNA polymerases, Annu Rev Biochem 71, 133-

163

45

21.4 Telomerase vervollständigt das 5´-Ende eines Folgestrangs

Kelleher C et al (2002) Telomerase, biochemical considerations for enzyme and

substrate, Trends Biochem Sci 27, 572-579

Blasco MA (2007) The epigenetic regulation of mammalian telomeres. Nature

Reviews Genetics, 8, 299-309.

Paeschke K, McDonald KR, & Zakian VA (2010) Telomeres: Structures in need of

unwinding. Febs Letters, 584, 3760-3772.

21.5 Die Replikation verläuft mit bemerkenswerter Präzision

Kunkel TA, Bebenek K (2004) DNA Replication Fidelity, Annu Rev Biochem 69, 497-

529

Diffley JF (2004) Regulation of early events in chromosome replication, Curr Biol 14,

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McCulloch SD & Kunkel TA (2008) The fidelity of DNA synthesis by eukaryotic

replicative and translesion synthesis polymerases. Cell Research, 18, 148-161.

(PDF)

Bloom LB (2009) Loading clamps for DNA replication and repair. Dna Repair, 8,

570-578. (PDF)

21.6 Die postreplikative Korrektur gewährleistet eine hohe Präzision

Schofield MJ, Hsieh P (2003) DNA mismatch repair: molecular mechanisms and

biological functions, Annu Rev Microbiol 57, 579-608

Opin Struct Biol 11, 47-52

Modrich P (2006) Mechanisms in eukaryotic mismatch repair. Journal of Biological

Chemistry, 281, 30305-30309. (PDF)

Burgers PMJ (2009) Polymerase Dynamics at the Eukaryotic DNA Replication Fork.

Journal of Biological Chemistry, 284, 4041-4045. (PDF)

21.7 Topoisomerasen entwinden DNA-Stränge

Espeli O, Marians KJ (2004) Untangling intracellular DNA topology, Mol Microbiol 52,

925-931

46

47

Schvarzman JB, Stasniak A (2004) A topological view of the replicon, EMBO Report

5, 256-261 (PDF)

Nitiss JL (2009) DNA topoisomerase II and its growing repertoire of biological

functions. Nature Reviews Cancer, 9, 327-337. (PDF)

Nitiss JL (2009) Targeting DNA topoisomerase II in cancer chemotherapy. Nature

Reviews Cancer, 9, 338-350. (PDF)

21.8 Nucleosomen werden während der Replikation neu verteilt

Mello JA, Almouzni G (2001) The ins and outs of nucleosome assembly, Curr Opin

Genet Dev 11, 136-141

Saha A, Wittmeyer J, & Cairns BR (2006) Chromatin remodelling: the industrial

revolution of DNA around histones. Nature Reviews Molecular Cell Biology, 7, 437-

447.

Groth A, Rocha W, Verreault A, & Almouzni G (2007) Chromatin challenges during

DNA replication and repair. Cell, 128, 721-733.

22 Analyse und Manipulation von Nucleinsäuren

22.1 Restriktionsendonucleasen spalten DNA an definierten Stellen

Nathans D, Smith HO (1975) Restriction endonucleases in the analysis and

restructuring of DNA molecules, Annu Rev Biochem 44, 273-293

Williams RJ (2003) Restriction endonucleases: classification, properties, and

applications, Mol Biotechnol 23, 225-243

Orlowski J & Bujnicki JM (2008) Structural and evolutionary classification of Type II

restriction enzymes based on theoretical and experimental analyses. Nucleic Acids

Research, 36, 3552-3569. (PDF)

22.2 DNA-Moleküle können rekombiniert werden

Cohen S et al (1973) Construction of biologically functional bacterial plasmids in vitro,

Proc Natl Acad Sci USA 70, 3240-44 (PDF)

Kan CC (2002) Impact of recombinant DNA technology and protein engineering on

structure-based drug design: case studies of HIV-1 and HCMV proteases, Curr Top

Med Chem 2, 247-269

Milligan G et al (2004) G protein-coupled receptor fusion proteins in drug discovery,

Curr Pharm Des 10, 1989-2001

Zuo PJ & Rabie ABM (2010) One-step DNA Fragment Assembly and Circularization

for Gene Cloning. Current Issues in Molecular Biology, 12, 11-16. (PDF)

22.3 Gezielter Kettenabbruch ermöglicht die Sequenzierung von DNA

Sanger F et al (1977) DNA sequencing with chain-terminating inhibitors, Proc Natl

Acad Sci USA 74, 5463-67 (Website)

Itakura K et al (1984) Synthesis and use of synthetic oligonucleotides, Annu Rev

Biochem 53, 323-356

Franca LT et al (2002) A review of DNA sequencing techniques, Q Rev Biophys 35,

169-200

Shendure J & Ji HL (2008) Next-generation DNA sequencing. Nature Biotechnology,

26, 1135-1145.

48

22.4 Nucleinsäuren können miteinander hybridisieren

Southern EM (1975) Detection of specific sequences among DNA fragments

separated by gel electrophoresis, J Mol Biol 98, 503-517

Wahl GM et al (1987) Northern and Southern blots, Meth Enzymol 152, 572-581

Croning MDR, Fricker DG, Komiyama NH, & Grant SGN (2010) Automated design of

genomic Southern blot probes. Bmc Genomics, 11. (PDF)

22.5 Die Hybridisierung ermöglicht eine chromosomale Lokalisation

Liehr T, Claussen U (2002) Current developments in human molecular cytogenetic

techniques, Curr Mol Med 2, 283-297

Jenkins G (2003) Unfolding large-scale maps, Genome 46, 947-952

Bartlett JM (2004) Fluorescence in situ hybridization: technical overview, Methods

Mol Med 97, 77-78

Langer S et al (2004) Multicolor chromosome painting in diagnostic and research,

Chromosome Res 12, 15-23

Jain KK (2004) Current status of fluorescent in-situ hybridisation, Med Device

Technol 15, 14-17

22.6 Die Polymerasekettenreaktion vervielfältigt definierte DNA-Abschnitte

Arnheim N, Erlich H (1992) Polymerase chain reaction strategy, Annu Rev Biochem

61, 131-156.

Mocellin S et al (2003) Quantitative real-time PCR: a powerful ally in cancer

research, Trends Mol Med 9, 189-195

Jobling MA, Gill P (2004) Encoded evidence: DNA in forensic analysis, Nature Rev

Gen 5, 739-750

VanGuilder HD, Vrana KE, & Freeman WM (2008) Twenty-five years of quantitative

PCR for gene expression analysis. Biotechniques, 44, 619-626. (PDF)

49

22.7 DNA-Bibliotheken erlauben die Identifizierung unbekannter Gene

Shizuya H et al (1992) Cloning and stable maintenance of 300 kbp fragments of

human DNA in E.coli using an F-factor-based vector, Proc Natl Acad Sci USA 89,

8794-97 (PDF)

Ying SY (2004) Complementary DNA libraries: an overview, Mol Biotechnol 27, 245-

252

Kasai K & Saeki Y (2006) DNA-based methods to prepare helper virus-free herpes

amplicon vectors and versatile design of amplicon vector plasmids. Current Gene

Therapy, 6, 303-314.

22.8 Polymorphismen helfen beim Auffinden krankheitsrelevanter Gene

Cullis CA (2002) The use of DNA polymorphisms in genetic mapping, Genet Eng 24,

179-189

Ogino S, Wilson RB (2004) Spinal muscular atrophy: molecular genetics and

diagnostics, Expert Rev Mol Diagn 4, 15-29

Altshuler D, Daly MJ, & Lander ES (2008) Genetic Mapping in Human Disease.

Science, 322, 881-888. (PDF)

22.9 Rekombinant exprimierte Proteine werden therapeutisch eingesetzt

Andersen DC, Krummen L (2002) Recombinant protein expression for therapeutic

applications, Curr Opin Biotechnol 13, 117-123

Kastrup J (2003) Therapeutic angiogenesis in ischemic heart disease: gene or

recombinant vascular growth factor protein therapy? Curr Gene Ther 3, 197-206

Walsh G & Jefferis R (2006) Post-translational modifications in the context of

therapeutic proteins. Nature Biotechnology, 24, 1241-1252.

22.10 Gezielte Mutagenese hilft bei der Aufklärung von Proteinfunktionen

Kristiansen K (2004) Molecular mechanisms of ligand binding, signaling, and

regulation within the superfamily of G-protein-coupled receptors: molecular modeling

and mutagenesis approaches to receptor structure and function, Pharmacol Ther

103, 21-80

50

de Graaf C, Oostenbrink C, Keizers PHJ, van Vugt-Lussenburg BMA, van

Waterschoot RAB, Tschirret-Guth RA, Commandeur JNM, & Vermeulen NPE (2007)

Molecular modeling-guided site-directed mutagenesis of cytochrome P450 2D6.

Current Drug Metabolism, 8, 59-77.

Yan Z, Sun X, & Engelhardt JF (2009) Progress and prospects: techniques for site-

directed mutagenesis in animal models. Gene Therapy, 16, 581-588. (PDF)

51

23 Veränderung genetischer Information

23.1 Transition und Transversion sind häufige Substitutionen

Courtois G & Gilmore TD (2006) Mutations in the NF-kappa B signaling pathway:

implications for human disease. Oncogene, 25, 6831-6843.

23.2 Die Reparatur von DNA erfolgt prompt und effizient

Sancar A et al (2004) Molecular Mechanisms of Mammalian DNA Repair and the

DNA Damage Checkpoints, Annu Rev Biochem 73, 39-85

Essen LO & Klar T (2006) Light-driven DNA repair by photolyases. Cellular and

Molecular Life Sciences, 63, 1266-1277.

Wyman C & Kanaar R (2006) DNA double-strand break repair: All's well that ends

well. Annual Review of Genetics, 40, 363-383.

23.3 Eliminierende Reparatursysteme sichern die Integrität der Erbinformationen

Moriwaki S, Kraemer KH (2001) Xeroderma pigmentosum – bridging a gap between

clinic and laboratory, Photodermatol Photoimmunol Photomed 17: 47-54

Sinha RP, Hader DP (2002) UV-induced DNA damage and repair: a review,

Photochem Photobiol Sci 1, 225-236

Cleaver JE (2005) Cancer in xeroderma pigmentosum and related disorders of DNA

repair. Nature Reviews Cancer, 5, 564-573.

Reardon JT & Sancar A (2006) Purification and characterization of Escherichia coli

and human nucleotide excision repair enzyme systems. Elsevier Academic Press

Inc., San Diego.

23.4 Die Neuverknüpfung von DNA sorgt für genetische Variabilität

Petronczki M et al (2003) Un ménage a quatre: the molecular biology of chromosome

segregation in meiosis, Cell 112, 423-440

52

Lynn A et al (2004) Variation in human meiotic recombination, Annu Rev Genomics

Hum Genet 5, 317-349

Liu Y, West SC (2004) Happy Hollidays: 40th anniversery of the Holliday junction,

Nat Rev Mol Cell Biol 5, 937-946

Neale MJ & Keeney S (2006) Clarifying the mechanics of DNA strand exchange in

meiotic recombination. Nature, 442, 153-158.

23.5 Die Auflösung der Strangkreuzung kann auf zwei Wegen erfolgen

Yamada K et al (2004) Three-dimensional structural views of branch migration and

resolution in DNA homologous recombination, Curr Opin Struct Biol 14, 130-137

Griffin CS, Thacker J (2004) The role of homologous recombination repair in the

formation of chromosome aberrations, Cytogenet Genome Res 104, 21-27

Cox MM (2007) Motoring along with the bacterial RecA protein. Nature Reviews

Molecular Cell Biology, 8, 127-138.

23.6 Die Antikörperdiversität beruht auf ortsgerichteter Rekombination

Oettinger MA (2004) How to keep V(D)J recombination under control, Immunol Rev

200, 165-181

Jung D, Giallourakis C, Mostoslavsky R, & Alt FW (2006) Mechanism and control of

V(D)J recombination at the immunoglobulin heavy chain locus. Annual Review of

Immunology, 24, 541-570.

Di Nola JM & Neuberger MS (2007) Molecular mechanisms of antibody somatic

hypermutation. Annual Review of Biochemistry, 76, 1-22.

Hewitt SL, Chaumeil J, & Skok JA (2010) Chromosome dynamics and the regulation

of V(D)J recombination. Immunological Reviews, 237, 43-54.

23.7 Ortsgerichtete Rekombination erzeugt die Vielfalt von T-Zell-Rezeptoren

Jones JM, Gellert M (2004) The taming of a transposon: V(D)J recombination and the

immune systeme, Immunol Rev 200, 233-248

Hersh MN et al (2004) Adaptive mutation and amplification in Escherichia coli: two

pathways of genome adaptation under stress, Res Microbiol 155, 352-359

53

Odegard VH & Schatz DG (2006) Targeting of somatic hypermutation. Nature

Reviews Immunology, 6, 573-583.

23.8 Transposons sind mobile Genelemente

Kazazian HH Jr (2004) Mobile elements: drivers of genome evolution, Science 303,

1626-32

Levy SB, Marshall B (2004) Antibacterial resistance worldwide: causes, challenges

and responses, Nat Med 10, S122-129

Wicker T, Sabot F, Hua-Van A, Bennetzen JL, Capy P, Chalhoub B, Flavell A, Leroy

P, Morgante M, Panaud O, Paux E, SanMiguel P, & Schulman AH (2007) A unified

classification system for eukaryotic transposable elements. Nature Reviews

Genetics, 8, 973-982.

23.9 Retroviren integrieren ihre DNA in das Wirtsgenom

Wu X, Burgess SM (2004) Integration target site selection for retroviruses and

transposable elements, Cell Mol Life Sci 61, 2588-96

Bennett PM (2004) Genome plasticity: insertion sequence elements, transposons and

integrons, and DNA rearrangement, Methods Mol Biol 266, 71-113

Goff SP (2007) Host factors exploited by retroviruses. Nature Reviews Microbiology,

5, 253-263.

Balvay L, Lastra ML, Sargueil B, Darlix JL, & Ohlmann T (2007) Translational control

of retroviruses. Nature Reviews Microbiology, 5, 128-140.

23.10 Transgene Tiere gestatten die funktionelle Analyse ausgewählter Genprodukte

Meister G, Tuschl T (2004) Mechanisms of gene silencing by double-stranded RNA,

Nature 431, 343-349

Medema RH (2004) Optimizing RNA interference for application in mammalian cells,

Biochem.J. 380, 593-603 (PDF)

Recillas-Targa F (2006) Multiple strategies for gene transfer, expression, knockdown,

and chromatin influence in mammalian cell lines and transgenic animals. Molecular

Biotechnology, 34, 337-354.

54

Venkatesh MN (2008) Transgenic animals and current scenario. Research Journal of

Biotechnology, 3, 53-63. (PDF)

23.11 Gentherapie ermöglicht die Behandlung von ererbten Erkrankungen

Gaspar HB et al (2003) Gene therapy progress and prospects: gene therapy for

severe combined immunodeficiency, Gene Ther 10, 1999-2004

Li SD & Huang L (2006) Gene therapy progress and prospects: non-viral gene

therapy by systemic delivery. Gene Therapy, 13, 1313-1319.

Waehler R, Russell SJ, & Curiel DT (2007) Engineering targeted viral vectors for

gene therapy. Nature Reviews Genetics, 8, 573-587.

23.12 Der Mensch entschlüsselt sein eigenes Genom

Austin CP (2004) The impact of the completed human genome sequence on the

development of novel therapeutics for human disease, Annu Rev Med 55, 1-13

Eichler EE et al (2004) An assessment of the sequence gaps: unfinished business in

a finished humane genome, Nat Rev Genet 5, 345-354

Nielsen R, Hellmann I, Hubisz M, Bustamante C, & Clark AG (2007) Recent and

ongoing selection in the human genome. Nature Reviews Genetics, 8, 857-868.

(PDF)

55

Teil IV Signaltransduktion an biologischen Membranen

24 Struktur und Dynamik biologischer Membranen

24.1 Phospholipide bilden in wässriger Lösung spontan Doppelschichten

Nagle JF, Tristram-Nagle S (2000) Lipid bilayer structure, Curr Opin Struct Biol 110,

474-480 (PDF)

Monnard PA, Deamer DW (2002) Membrane self-assembly processes: steps toward

the first cellular life, Anat Rec 268, 196-207 (PDF)

Carmona-Ribeiro AM (2006) Lipid bilayer fragments and disks in drug delivery.

Current Medicinal Chemistry, 13, 1359-1370.

Feigenson GW (2009) Phase diagrams and lipid domains in multicomponent lipid

bilayer mixtures. Biochimica et Biophysica Acta-Biomembranes, 1788, 47-52. (PDF)

24.2 Biologische Membranen sind dynamische Strukturen

Jacbson K et al (1995) Revisiting the fluid mosaic model of membranes, Science

268, 1441-42

Bagatolli LA (2006) To see or not to see: Lateral organization of biological

membranes and fluorescence microscopy. Biochimica et Biophysica Acta-

Biomembranes, 1758, 1541-1556.

van Meer G, Voelker DR, & Feigenson GW (2008) Membrane lipids: where they are

and how they behave. Nature Reviews Molecular Cell Biology, 9, 112-124. (PDF)

Elson EL, Fried E, Dolbow JE, & Genin GM (2010) Phase Separation in Biological

Membranes: Integration of Theory and Experiment. ANNUAL REVIEWS, PALO

ALTO.

24.3 Lipidmembranen verfügen über eine selektive Permeabilität

Holsbeeks I et al (2004) The eukaryotic plasma membrane as a nutrient-sensing

device, Trends Biochem Sci 29, 556-564

56

Chen RRZ (2007) Permeability issues in whole-cell bioprocesses and cellular

membrane engineering. Applied Microbiology and Biotechnology, 74, 730-738.

24.4 Biologische Membranen sind asymmetrisch und geladen

Devaux PF, Morris R (2004) Transmembrane asymmetry and lateral domains in

biological membranes, Traffic 5, 241-246

Fadeel B & Xue D (2009) The ins and outs of phospholipid asymmetry in the plasma

membrane: roles in health and disease. Critical Reviews in Biochemistry and

Molecular Biology, 44, 264-277. (PDF)

24.5 Das endoplasmatische Reticulum produziert asymmetrische Membranen

Sanyat S & Menon AK (2009) Flipping Lipids: Why an' What's the Reason for? Acs

Chemical Biology, 4, 895-909.

Contreras FX, Sanchez-Magraner L, Alonso A, & Goni FM (2010) Transbilayer (flip-

flop) lipid motion and lipid scrambling in membranes. Febs Letters, 584, 1779-1786.

24.6 Die Verteilung von Lipiden und Proteinen in biologischen Membranen schwankt

Parton RG, Hancock JF (2004) Lipid rafts and plasma membrane microorganization:

insights from Ras, Trends Cell Biol 14, 141-147

Hancock JF (2006) Lipid rafts: contentious only from simplistic standpoints. Nature

Reviews Molecular Cell Biology, 7, 456-462. (PDF)

Jacobson K, Mouritsen OG, & Anderson RGW (2007) Lipid rafts: at a crossroad

between cell biology and physics. Nature Cell Biology, 9, 7-14.

Parton RG & Simons K (2007) The multiple faces of caveolae. Nature Reviews

Molecular Cell Biology, 8, 185-194.

24.7 Funktionelle Membransysteme können rekonstituiert werden

Silvius JR (1992) Solubilization and functional reconstitution of biomembrane

components, Annu Rev Biophys Biomol Struct 21, 323-348

57

58

Seddon AM et al (2004) Membrane proteins, lipids and detergents: not just a soap

opera, Biochim Biophys Acta 1666, 105-117

Liguori L & Lenormand JL (2009) Production of Recombinant Proteoliposomes for

Therapeutic Uses. Elsevier Academic Press Inc., San Diego.

Ritchie TK, Grinkova YV, Bayburt TH, Denisov IG, Zolnerciks JK, Atkins WM, &

Sligar SG (2009) Reconstitution of Membrane Proteins in Phospholipid Bilayer

Nanodiscs. Elsevier Academic Press Inc., San Diego.

25 Proteine als Funktionsträger von Biomembranen

25.1 Integrale Proteine durchspannen biologische Membranen

Doura AK, Fleming KG (2004) Complex interactions at the helix-helix interface

stabilize the glycophorin A transmembrane dimer, J Mol Biol 343,1487-97

Opin Struct Biol 8, 640-648

MacKenzie KR (2006) Folding and stability of alpha-helical integral membrane

proteins. Chemical Reviews, 106, 1931-1977.

Speers AE & Wu CC (2007) Proteomics of integral membrane proteins-theory and

application. Chemical Reviews, 107, 3687-3714.

25.2 Periphere Membranproteine binden einseitig an die Lipidschicht

Linder ME, Deschenes RJ (2003) New insights into the mechanisms of protein

palmitoylation, Biochem 42, 4311-20

Resh MD (2004) Membrane targeting of lipid modified signal transduction proteins,

Subcell Biochem 37, 217-32

Cheng TL & Roffler S (2008) Membrane-Tethered Proteins for Basic Research,

Imaging, and Therapy. Medicinal Research Reviews, 28, 885-928.

25.3 Membranproteine bewegen sich in der Lipidschicht

Jaskolski F & Henley JM (2009) Synaptic Receptor Trafficking: the Lateral Point of

View. Neuroscience, 158, 19-24.

Rayan G, Guet JE, Taulier N, Pincet F, & Urbach W (2010) Recent Applications of

Fluorescence Recovery after Photobleaching (FRAP) to Membrane Bio-

Macromolecules. Sensors, 10, 5927-5948. (PDF)

25.4 Membranproteine verleihen Membranen ihre funktionelle Vielfalt

Gahmerg CG, Tolvanen M (1996) Why mammalian cell surface proteins are

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59

60

Sperandio M (2006) Selectins and glycosyltransferases in leukocyte rolling in vivo.

Febs Journal, 273, 4377-4389.

25.5 Transportproteine vermitteln regen Stoffaustausch über Membranen

Huang Y & Sadee W (2006) Membrane transporters and channels in

chemoresistance and -sensitivity of tumor cells. Cancer Letters, 239, 168-182.

25.6 Transport über Membranen kann uni- oder bidirektional sein

Philipson KD, Nicoll DA (2000) Sodium-calcium exchange: a molecular approach,

Annu Rev Physiol 62, 111-133

Zhao FQ & Keating AF (2007) Functional properties and genomics of glucose

transporters. Current Genomics, 8, 113-128. (PDF)

Abramson J & Wright EM (2009) Structure and function of Na+-symporters with

inverted repeats. Current Opinion in Structural Biology, 19, 425-432.

25.7 Pumpen und Kanäle schleusen Ionen über Membranbarrieren

Jentsch T et al (2004) Ion channels: function unravelled by dysfunction, Nature Cell

Biol 6, 1039-37

DeFelice LJ (2004) Going against the flow, Nature 432, 279

Piddock LJ (2006) Multidrug-resistance efflux pumps - not just for resistance. Nature

Reviews Microbiology, 4, 629-636.

Tadini-Buoninsegni F, Bartolornmei G, Moncelli MR, & Fendler K (2008) Charge

transfer in P-type ATPases investigated on planar membranes. Archives of

Biochemistry and Biophysics, 476, 75-86.

26 Ionenpumpen und Membrankanäle

26.1 Die Na+-K+-ATPase arbeitet im Antiport-Modus

Kaplan JH (2002) Biochemistry of NA,K-ATPase, Annu Rev Biochem 71, 511-35

Jorgensen PL et al (2003) Structure and mechanism of Na,K-ATPase: Functional

sites and their interaction, Annu Rev Physiol 66, 817-849

Poulsen H, Morth P, Egebjerg J, & Nissen P (2010) Phosphorylation of the Na+,K+-

ATPase and the H+,K+-ATPase. Febs Letters, 584, 2589-2595.

26.2 Ionengradienten treiben den Stofftranport über Membranen an

Toyoshima C, InesiI G (2004) Strucural Basis of Ion Pumping by Ca2+-ATPase of the

Sarcoplasmic Reticulum, Annu Rev Biochem 73, 269-92

Toyoshima C (2008) Structural aspects of ion pumping by Ca2+-ATPase of

sarcoplasmic reticulum. Archives of Biochemistry and Biophysics, 476, 3-11.

26.3 Protonentransporter entsorgen die zellulären H+-Lasten

Subramaniam S (1999) The structure of bacteriorhodopsin: an emerging consensus,

Curr Opin Struct Biol 9, 462-468

Padan E, Kozachkov L, Herz K, & Rimon A (2009) NhaA crystal structure: functional-

structural insights. Journal of Experimental Biology, 212, 1593-1603.

Hirai T, Subramaniam S, & Lanyi JK (2009) Structural snapshots of conformational

changes in a seven-helix membrane protein: lessons from bacteriorhodopsin. Current

Opinion in Structural Biology, 19, 433-439. (PDF)

Tian P (2010) Computational protein design, from single domain soluble proteins to

membrane proteins. Chemical Society Reviews, 39, 2071-2082.

26.4 ABC-Transporter verfrachten Ionen, Lipide und Arzneimittel über Membranen

McCarty NA (2000) Permeation through the CFTR chloride channel, J Exp Biol 203,

1947-62 (PDF)

61

Borst P, Elferink RO (2002) Mammalian ABC Transporters in Health and Disease,

Annu Rev Biochem 71, 537-92

Guggino WB & Stanton BA (2006) New insights into cystic fibrosis: molecular

switches that regulate CFTR. Nature Reviews Molecular Cell Biology, 7, 426-436.

Rees DC, Johnson E, & Lewinson O (2009) ABC transporters: the power to change.

Nature Reviews Molecular Cell Biology, 10, 218-227. (PDF)

26.5 Ionenkanäle bilden temporäre Poren in der Membran

Miloshevsky GV, Jordan PC (2004) Permeation in ion channels: the interplay

between structure and theory, Trends Neurosci 27, 308-314

Owsianik G, Talavera K, Voets T, & Nilius B (2006) Permeation and selectivity of

TRP channels. Annual Review of Physiology, 68, 685-717.

26.6 Spannungsgesteuerte Ionenkanäle sondieren Potenzialänderungen

Kaczmarek LK (2006) Non-conducting functions of voltage-gated ion channels.

Nature Reviews Neuroscience, 7, 761-771.

Dai SP, Hall DD, & Hell JW (2009) Supramolecular Assemblies and Localized

Regulation of Voltage-Gated Ion Channels. Physiological Reviews, 89, 411-452.

(PDF)

26.7 Der nicotinische Acetylcholinrezeptor ist ein ligandengesteuerter Ionenkanal

Utkin Y et al (2000) Structural organization of nicotinic acetylcholin receptors, Membr

Cell Biol 13, 143-164

Miyazawa A et al (2003) Structure and gating mechanism of the acetylcholin receptor

pore, Nature 432, 949-955

Albuquerque EX, Pereira EFR, Alkondon M, & Rogers SW (2009) Mammalian

Nicotinic Acetylcholine Receptors: From Structure to Function. Physiological

Reviews, 89, 73-120. (PDF)

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63

26.8 Liganden steuern die Öffnung der Rezeptorschleuse

Neher E, Sakmann B (1992) The patch-clamp technique, Sci Am 266(3), 28-35

Maksay G (2009) Ligand-gated pentameric ion channels, from binding to gating. Curr

Mol Pharmacol, 2.

26.9 Zellporen erlauben den Stoffaustausch zwischen Nachbarzellen

Unger VM et al (1999) Three-dimensional structure of a recombinant gap junction

membrane channel, Science 283, 1176-1180

Stout C et al (2004) Connexins: functions without junctions, Curr Opin Cell Biol 16:

507-512

Bloomfield SA & Volgyi B (2009) The diverse functional roles and regulation of

neuronal gap junctions in the retina. Nature Reviews Neuroscience, 10, 495-506.

27 Prinzipien der interzellulären Kommunikation

27.1 Interzelluläre Kommunikation nutzt mehrere Modalitäten

Drucker DJ (2007) The role of gut hormones in glucose homeostasis. Journal of

Clinical Investigation, 117, 24-32. (PDF)

27.2 Endokrine Signalsysteme sind selektiv, amplifizierend und flexibel

Bokoch MP, Zou YZ, Rasmussen SGF, Liu CW, Nygaard R, Rosenbaum DM, Fung

JJ, Choi HJ, Thian FS, Kobilka TS, Puglisi JD, Weis WI, Pardo L, Prosser RS,

Mueller L, & Kobilka BK (2010) Ligand-specific regulation of the extracellular surface

of a G-protein-coupled receptor. Nature, 463, 108-U121. (PDF)

27.3 Fundamentale Signalwege vermitteln die interzelluläre Kommunikation

Taniguchi CM, Emanuelli B, & Kahn CR (2006) Critical nodes in signalling pathways:

insights into insulin action. Nature Reviews Molecular Cell Biology, 7, 85-96.

Pilecka I, Whatmore A, van Huijsduijnen RH, Destenaves B, & Clayton P (2007)

Growth hormone signalling: sprouting links between pathways, human genetics and

therapeutic options. Trends in Endocrinology and Metabolism, 18, 12-18.

27.4 Intrazelluläre Rezeptoren wirken als Transkriptionsfaktoren

Dilworth FJ, Chambon P (2001) Nuclear receptors coordinate the activities of

chromatin remodeling complexes and coactivators to facilitate initiation of

transcription, Oncogene 20, 3047-3054 (PDF)

Evans R (2004) A transcriptional basis for physiology, Nat Med 10, 1022-1026

Bain DL, Heneghan AF, Connaghan-Jones KD, & Miura MT (2007) Nuclear receptor

structure: Implications for function. Annual Review of Physiology, 69, 201-220.

Cheng SY, Leonard JL, & Davis PJ (2010) Molecular Aspects of Thyroid Hormone

Actions. Endocrine Reviews, 31, 139-170.

64

27.5 Stickstoffmonoxid ist ein gasförmiger Botenstoff

Bredt DS (2003) Nitric oxide signaling specificity – the heart of the problem, J Cell Sci

1, 9-15 (PDF)

Moncada S & Bolanos JP (2006) Nitric oxide, cell bioenergetics and

neurodegeneration. Journal of Neurochemistry, 97, 1676-1689.

Cary SPL, Winger JA, Derbyshire ER, & Marletta MA (2006) Nitric oxide signaling: no

longer simply on or off. Trends in Biochemical Sciences, 31, 231-239.

27.6 Proteohormone werden aus inaktiven Vorstufen freigesetzt

Tanaka S (2004) Comparative aspects of intracellular proteolytic processing of

peptide hormone precursors: studies of proopiomelanocortin processing, Zoolog Sci

20,1183-1198

Michael DJ, Cai HJ, Xiong WY, Ouyang J, & Chow RH (2006) Mechanisms of

peptide hormone secretion. Trends in Endocrinology and Metabolism, 17, 408-415.

27.7 Zelloberflächenrezeptoren aktivieren intrazelluläre Signalkaskaden

Scott JD, Pawson T (2000) Cell Communication, The Inside Story, Sci Amer 282,

June: 54-61

Schlessinger J & Lemmon MA (2006) Nuclear signaling by receptor tyrosine kinases:

The first robin of spring. Cell, 127, 45-48.

Hanson MA & Stevens RC (2009) Discovery of New GPCR Biology: One Receptor

Structure at a Time. Structure, 17, 8-14. (PDF)

27.8 GTP-bindende Proteine verknüpfen Signalketten

Neves SR et al (2002) G protein pathways, Science 296, 1636-1639

Bos JL, Rehmann H, & Wittinghofer A (2007) GEFs and GAPs: Critical elements in

the control of small G proteins. Cell, 129, 865-877.

Marrari Y, Crouthamel M, Irannejad R, & Wedegaertner PB (2007) Assembly and

trafficking of heterotrimeric G proteins. Biochemistry, 46, 7665-7677. (PDF)

Gasper R, Meyer S, Gotthardt K, Sirajuddin M, & Wittinghofer A (2009) It takes two to

tango: regulation of G proteins by dimerization. Nature Reviews Molecular Cell

Biology, 10, 423-429.

65

66

27.9 Effektoren integrieren Signale verschiedener Rezeptoren

Tan X et al (2003) Integration of G-protein coupled receptor signaling pathways for

activation of a transcription factor (EGR-3). Genomics Proteomics Bioinformatics 1,

173-179

Tiyyagura SR et al (2004) Reciprocal regulation and integration of signaling by

intracellular calcium and cyclic GMP, Vitam Horm 69, 69-94

Sadler AJ & Williams BRG (2008) Interferon-inducible antiviral effectors. Nature

Reviews Immunology, 8, 559-568. (PDF)

Milano A, De Rosa V, Iaffaioli RV, & Caponigro F (2007) Downstream intracellular

effectors of epidermal growth factor receptor as targets for anticancer therapy. Expert

Opinion on Therapeutic Targets, 11, 771-782.

28 Signaltransduktion über G-Protein-gekoppelte Rezeptoren

28.1 G-Protein-gekoppelte Rezeptoren durchspannen siebenmal die Membran

Ross EM, Wilkie TM (2000) GTPase-Activating Proteins for Heterotrimeric G

Proteins, Regulators of G Protein Signaling (RGS) and RGS-like Proteins, Annu Rev

Biochem 69, 795-827 (PDF)

Dohlman HG, Thorner JW (2001) Regulation of G-Protein-Initiated Signal

Transduction in Yeast, Paradigms and Principles, Annu Rev Biochem 70, 703-54

Congreve M & Marshall F (2010) The impact of GPCR structures on pharmacology

and structure-based drug design. British Journal of Pharmacology, 159, 986-996.

28.2 G-Proteine modulieren die Aktivität von Adenylat-Cyclase

Lencer WI, Tsai B (2003) The intracellular voyage of cholera toxin, going retro,

Trends Biochem Sci 28, 639-645

Rebois RV, Robitaille M, Gales C, Dupre DJ, Baragli A, Trieu P, Ethier N, Bouvier M,

& Hebert TE (2006) Heterotrimeric G proteins form stable complexes with adenylyl

cyclase and Kir3.1 channels in living cells. Journal of Cell Science, 119, 2807-2818.

(PDF)

Willoughby D & Cooper DMF (2007) Organization and Ca2+ regulation of adenylyl

cyclases in cAMP microdomains. Physiological Reviews, 87, 965-1010. (PDF)

28.3 Kinasen phosphorylieren und desensitivieren G-Protein-gekoppelte Rezeptoren

Ribas C et al (2007) The G protein-coupled receptor kinase (GRK) interactome: Role

of GRKs in GPCR regulation and signaling. Biochimica et Biophysica Acta-

Biomembranes, 1768, 913-922.

Kendall RT & Luttrell LM (2009) Diversity in arrestin function. Cellular and Molecular

Life Sciences, 66, 2953-2973.

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28.4 Die Rezeptorendocytose benutzt clathrinbeschichtete Vesikel

Marchese A et al (2003) The ins and outs of G-protein-coupled receptor trafficking,

Trends Biochem Sci 28, 369-376

McNiven MA & Thompson HM (2006) Vesicle formation at the plasma membrane

and trans-Golgi network: The same but different. Science, 313, 1591-1594.

Wolfe BL & Trejo J (2007) Clathrin-dependent mechanisms of G protein-coupled

receptor endocytosis. Traffic, 8, 462-470.

28.5 cAMP steuert über Transkriptionsfaktoren die Genexpression

Brivanlou AH, Darnell JE (2002) Signal transduction and the control of gene

expression, Science 295, 813-818

Kitagawa K (2007) CREB and cAMP response element-mediated gene expression in

the ischemic brain. Febs Journal, 274, 3210-3217.

Benito E & Barco A (2010) CREB's control of intrinsic and synaptic plasticity:

implications for CREB-dependent memory models. Trends in Neurosciences, 33,

230-240.

28.6 Sinneszellen nutzen G-Protein-abhängige Signalwege

Buck LB (2000) The molecular architecture of odor and pheromone sensing in

mammals, Cell 100, 611-618

Ridge KD et al (2003) Phototransduction, crystal clear, Trends Biochem Sci 28, 479-

487

Palczewski K (2006) G protein-coupled receptor rhodopsin. Annual Review of

Biochemistry, 75, 743-767. (PDF)

Yau KW & Hardie RC (2009) Phototransduction Motifs and Variations. Cell, 139, 246-

264. (PDF)

Su CY, Menuz K, & Carlson JR (2009) Olfactory Perception: Receptors, Cells, and

Circuits. Cell, 139, 45-59.

28.7 Inositoltrisphosphat setzt Ca2+ aus intrazellulären Speichern frei

Patterson RL et al (2004) Inositol 1,4,5-Trisphosphate Receptors as Signal

Integrators, Annu Rev Biochem 73, 437-64

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69

Carafolie E (2004) Calcium-mediated cellular signals, a story of failures, Trends

Biochem Sci 29, 371-379

Mikoshiba K (2007) IP3 receptor/Ca2+ channel: from discovery to new signaling

concepts. Journal of Neurochemistry, 102, 1426-1446.

Joseph SK & Hajnoczky G (2007) IP3 receptors in cell survival and apoptosis: Ca2+

release and beyond. Apoptosis, 12, 951-968.

28.8 Ca2+ und Calmodulin wirken im Duett

Chin D, Means AR (2000) Calmodulin : a prototypical calcium sensor, Trends Cell

Biol 10, 322-328

Corcoran EE, Means AR (2001) Defining Ca2+/calmodulin-dependent protein kinase

cascades in transcriptional regulation, J Biol Chem 276, 2975-78 (PDF)

Al-Shanti N & Stewart CE (2009) Ca2+/calmodulin-dependent transcriptional

pathways: potential mediators of skeletal muscle growth and development. Biological

Reviews, 84, 637-652.

28.9 Diacylglycerin aktiviert Proteinkinase C

Spitaler M, Cantrell DA (2004) Protein kinase C and beyond, Nat Immunol 5, 785-790

Newton AC (2004) Diacylglycerol's affair with protein kinase C turns 25, Trends

Pharmacol Sci 25, 175-177

Wang QMJ (2006) PKD at the crossroads of DAG and PKC signaling. Trends in

Pharmacological Sciences, 27, 317-323.

29 Signaltransduktion über enzymgekoppelte Rezeptoren

29.1 Enzymgekoppelte Rezeptoren besitzen meist Tyrosin-Kinase-Aktivität

Schlessinger J (2000) Cell signaling by receptor tyrosin kinases, Cell 103,211-225

Cross MJ et al (2003) VEGF-receptor signal transduction, Trends Biochem Sci 28,

488-494

Dengjel J, Kratchmarova I, & Blagoev B (2009) Receptor tyrosine kinase signaling: a

view from quantitative proteomics. Molecular Biosystems, 5, 1112-1121.

29.2 Liganden induzieren Dimerisierung und Autophosphorylierung

Schlessinger J (2002) Ligand-induced, receptor-mediated dimerization and activation

of EGF receptor, Cell 110, 669-672

Bae JH & Schlessinger J (2010) Asymmetric tyrosine kinase arrangements in

activation or autophosphorylation of receptor tyrosine kinases. Molecules and Cells,

29, 443-448.

29.3 Enzymgekoppelte Rezeptoren aktivieren monomere G-Proteine

Corbett KD, Alber T (2001) The many faces of Ras, recognition of small GTP-binding

proteins, Trends Biochem Sci 26, 710-716

Harden TK & Sondek J (2006) Regulation of phospholipase C isozymes by Ras

superfamily GTPases. Annual Review of Pharmacology and Toxicology, 46, 355-379.

Karnoub AE & Weinberg RA (2008) Ras oncogenes: split personalities. Nature

Reviews Molecular Cell Biology, 9, 517-531.

29.4 GTP-Ras aktiviert den MAP-Kinasen-Signalweg

Chang L, Karin M (2001) Mammalian MAP kinase signalling cascades, Nature 410,

37-40

Buchwalter G, Gross C, & Wasylyk B (2004) Ets ternary complex transcription

factors. Gene, 324, 1-14.

70

Dhillon AS, Hagan S, Rath O, & Kolch W (2007) MAP kinase signalling pathways in

cancer. Oncogene, 26, 3279-3290.

29.5 Mutierte Signalproteine haben onkogenes Potenzial

Blume-Jensen P, Hunter T (2001) Oncogenic kinase signaling, Nature 411, 355-365

Rajalingam K, Schreck R, Rapp UR, & Albert S (2007) Ras oncogenes and their

downstream targets. Biochimica et Biophysica Acta-Molecular Cell Research, 1773,

1177-1195.

Krab LC, Goorden SMI, & Elgersma Y (2008) Oncogenes on my mind: ERK and

MTOR signaling in cognitive diseases. Trends in Genetics, 24, 498-510.

29.6 Cytokine benutzen Tyrosin-Kinase-assoziierte Rezeptoren

Attisano L, Wranna JL (2002) Signal transduction by the TGF- β superfamily, Science

296, 1646-47

Aaronson DS, Horvath CM (2002) A roadmap for those who don´t know JAK-STAT,

Science 296, 1653-55

Schindler C, Levy DE, & Decker T (2007) JAK-STAT signaling: From interferons to

cytokines. Journal of Biological Chemistry, 282, 20059-20063. (PDF)

Steinberg GR, Watt MJ, & Febbraio MA (2009) Cytokine regulation of AMPK

signalling. Frontiers in Bioscience, 14, 1902-1916.

29.7 Integrine sind zellmatrixassoziierte Rezeptoren

Humphries MJ et al (2003) Integrin structure, heady advances in ligand binding, but

activation still makes the knees wobble, Trends Biochem Sci 28/6, 313-320

Fagerholm S et al (2004) P marks the spot, site-specific integrin phosphorylation

regulates molecular interactions, Trends Biochem Sci 29, 504-512

Arnaout MA, Goodman SL, & Xiong JP (2007) Structure and mechanics of integrin-

based cell adhesion. Current Opinion in Cell Biology, 19, 495-507. (PDF)

Gahmberg CG, Fagerholm SC, Nurmi SM, Chavakis T, Marchesan S, & Gronholm M

(2009) Regulation of integrin activity and signalling. Biochimica et Biophysica Acta-

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30 Hormonelle Steuerung komplexer Systeme

30.1 Regulation des kardiovaskulären Systems

Lowenstein CJ (2007) Nitric oxide regulation of protein trafficking in the

cardiovascular system. Cardiovascular Research, 75, 240-246. (PDF)

Hendriks-Balk MC, Peters SLM, Michel MC, & Alewijnse AE (2008) Regulation of G

protein-coupled receptor signalling: Focus on the cardiovascular system and

regulator of G protein signalling proteins. European Journal of Pharmacology, 585,

278-291.

30.2 Regulation von Wasser- und Elektrolythaushalt

Ruilope LM (2008) Angiotensin receptor blockers: RAAS blockade and

renoprotection. Current Medical Research and Opinion, 24, 1285-1293.

Brown D, Hasler U, Nunes P, Bouley R, & Lu HAJ (2008) Phosphorylation events

and the modulation of aquaporin 2 cell surface expression. Current Opinion in

Nephrology and Hypertension, 17, 491-498.

30.3 Steuerung von Calcium- und Phosphathaushalt

Wada T, Nakashima T, Hiroshi N, & Penninger JM (2006) RANKL-RANK signaling in

osteoclastogenesis and bone disease. Trends in Molecular Medicine, 12, 17-25.

30.4 Molekulare Basis von Wachstum und Entwicklung

Kurmasheva RT & Houghton PJ (2006) IGF-I mediated survival pathways in normal

and malignant cells. Biochimica et Biophysica Acta-Reviews on Cancer, 1766, 1-22.

Sami AJ (2007) Structure-function relation of somatotropin with reference to

molecular Modeling. Current Protein & Peptide Science, 8, 283-292.

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30.5 Hormonelle Regulation in reproduktiven Sytemen

Hunzicker-Dunn M & Maizels ET (2006) FSH signaling pathways in immature

granulosa cells that regulate target gene expression: Branching out from protein

kinase A. Cellular Signalling, 18, 1351-1359. (PDF)

Palermo R (2007) Differential actions of FSH and LH during folliculogenesis.

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31 Molekulare Physiologie des Gastrointestinaltrakts

31.1 Hormonelle Regelwerke im Magen

Kusters JG, van Vliet AHM, & Kuipers EJ (2006) Pathogenesis of Helicobacter pylori

infection. Clinical Microbiology Reviews, 19, 449-90. (PDF)

Forte JG & Zhu LX (2010) Apical Recycling of the Gastric Parietal Cell H,K-ATPase.

Annual Review of Physiology, 72, 273-296.

31.2 Molekulare Mechanismen von Digestion und Resorption

Lomer MCE, Parkes GC, & Sanderson JD (2008) Review article: lactose intolerance

in clinical practice - myths and realities. Alimentary Pharmacology & Therapeutics,

27, 93-103. (PDF)

Borghese MFA & Majowicz MP (2009) Inhibitors of Sodium/Glucose Cotransport.

Drugs of the Future, 34, 297-305.

31.3 Hormonelle Steuerung des exokrinen Pankreas

Alrefai WA & Gill RK (2007) Bile acid transporters: Structure, function, regulation and

pathophysiological implications. Pharmaceutical Research, 24, 1803-1823.

Czako L, Hegyi P, Rakonczay Z, Wittmann T, & Otsuki M (2009) Interactions

between the Endocrine and Exocrine Pancreas and Their Clinical Relevance.

Pancreatology, 9, 351-359. (PDF)

31.4 Hormonelle Steuerung des Glucosemetabolismus

Bansal P & Wang QH (2008) Insulin as a physiological modulator of glucagon

secretion. American Journal of Physiology-Endocrinology and Metabolism, 295,

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32 Neuronale Erregung und Transmission

32.1 An der Zellmembran entsteht ein Ruhepotenzial

Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its

application to conduction and excitation in nerve, J Physiol 117, 500-544 (PDF)

Sundelacruz S, Levin M, & Kaplan DL (2009) Role of Membrane Potential in the

Regulation of Cell Proliferation and Differentiation. Stem Cell Reviews and Reports,

5, 231-246.

32.2 Der K+-Gradient bestimmt vorwiegend das Ruhepotenzial

Kurata HT & Fedida D (2006) A structural interpretation of voltage-gated potassium

channel inactivation. Progress in Biophysics & Molecular Biology, 92, 185-208.

Ashcroft FM (2006) From molecule to malady. Nature, 440, 440-447.

32.3 Nervenzellen können auf einen Reiz mit einem Aktionspotenzial reagieren

Acebes A, Ferrus A (2000) Cellular and molecular features of axon collaterals and

dendrites, Trends Neurosci 23, 557-565

Lai HC & Jan LY (2006) The distribution and targeting of neuronal voltage-gated ion

channels. Nature Reviews Neuroscience, 7, 548-562.

Borjesson SI & Elinder F (2008) Structure, Function, and Modification of the Voltage

Sensor in Voltage-Gated Ion Channels. Cell Biochemistry and Biophysics, 52, 149-

174.

32.4 Aktionspotenziale verlaufen unidirektional, stereotyp und oft saltatorisch

Chotard C, Salecker I (2004) Neurons and glia: team players in axon guidance,

Trends Neurosci 27, 655-661

Kim S, Chiba A (2004) Dendritic guidance, Trends Neurosci 27, 195-202

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Bean BP (2007) The action potential in mammalian central neurons. Nature Reviews

Neuroscience, 8, 451-465.

Baranauskas G (2007) Ionic Channel Function in Action Potential Generation:

Current Perspective. Molecular Neurobiology, 35, 129-150.

32.5 Neurotransmitter übertragen Botenschaften an chemischen Synapsen

Kiehn O, Tresch MC (2002) Gap junctions and motor behavior, Trends Neurosci 25,

108-115

Haydon PG & Carmignoto G (2006) Astrocyte control of synaptic transmission and

neurovascular coupling. Physiological Reviews, 86, 1009-1031. (PDF)

Rizo J, Chen XC, & Arac D (2006) Unraveling the mechanisms of synaptotagmin and

SNARE function in neurotransmitter release. Trends in Cell Biology, 16, 339-350.

32.6 Neurotransmitter können exzitatorisch oder inhibitorisch wirken

Mayer ML (2004) Structure and function of glutamate receptor ion channels, Annu

Rev Physiol 66, 161-181

Craig AM, Graf ER, & Linhoff MW (2006) How to build a central synapse: clues from

cell culture. Trends in Neurosciences, 29, 8-20. (PDF)

Ben-Ari Y, Gaiarsa JL, Tyzio R, & Khazipov R (2007) GABA: A pioneer transmitter

that excites immature neurons and generates primitive oscillations. Physiological

Reviews, 87, 1215-1284. (PDF)

Lau CG & Zukin RS (2007) NMDA receptor trafficking in synaptic plasticity and

neuropsychiatric disorders. Nature Reviews Neuroscience, 8, 413-426.

32.7 Katecholamine steuern elementare neuronale Prozesse

Oberbeck R (2006) Catecholamines: Physiological Immunomodulators During Health

and Illness. Current Medicinal Chemistry, 13, 1979-1989.

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32.8 Neuropeptide und Toxine modulieren die synaptische Aktivität

Horner PJ, Gage FH (2000) Regenerating the damaged central nervous system,

Nature 407, 963-970

Rossetto O, Morbiato L, Caccin P, Rigoni M, & Montecucco C (2006) Presynaptic

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33 Struktur und Dynamik des Cytoskeletts

33.1 Mikrotubuli sind dynamische Strukturen des Cytoskeletts

Nogales E (2000) Structural Insights into Mikrotubule Function, Annu Rev Biochem

69, 277-302

Job D et al (2003) Microtubule nucleation, Curr Opin Cell Biol 15, 111-117

Luders J & Stearns T (2007) Microtubule-organizing centres: a re-evaluation. Nature

Reviews Molecular Cell Biology, 8, 161-167.

Akhmanova A & Steinmetz MO (2008) Tracking the ends: a dynamic protein network

controls the fate of microtubule tips. Nature Reviews Molecular Cell Biology, 9, 309-

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33.2 Intermediärfilamente verleihen mechanische Widerstandsfähigkeit

Garrod DR et al (2002) Desmosomal cadherins, Curr Opin Cell Biol 14, 537-545

Herrmann H, Aebi U (2004) Intermediate Filaments, Molecular Structure, Assembly

Mechanism, and Integration into Functionally Distinct Intracellular Scaffolds, Annu

Rev Biochem 73, 749-89

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from cell architecture to nanomechanics. Nature Reviews Molecular Cell Biology, 8,

562-573.

Hyder CL, Pallari HM, Kochin V, & Eriksson JE (2008) Providing cellular signposts -

Post-translational modifications of intermediate filaments. Febs Letters, 582, 2140-

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33.3 Die Aggregation von Actin zu Filamenten ist strikt reguliert

McGough AM, Staiger CJ, Min JK, & Simonetti KD (2003) The gelsolin family of actin

regulatory proteins: modular structures, versatile functions. Febs Letters, 552, 75-81.

Wear M, Cooper J (2004) Capping protein, new insights into mechanism and

regulation, Trends Biochem Sci 29, 418-428

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unfolding and aggregation of actin - Stabilization and destabilization of actin

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33.4 Actinbindende Proteine bündeln und vernetzen Einzelfilamente

Winder SJ (2003) Structural insights into actin-binding, branching and bundling

proteins, Curr Opin Cell Biol 15, 14-22

Pak CW, Flynn KC, & Bamburg JR (2008) Actin-binding proteins take the reins in

growth cones. Nature Reviews Neuroscience, 9, 136-147.

Khurana S & George SP (2008) Regulation of cell structure and function by actin-

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33.5 Actinfilamente formieren sich zu Gerüstwerken in der Zelle

Campbell I, Ginsberg M (2004) The talin-tail interaction places integrin activation on

FERM ground, Trends Biochem Sci 29, 429-435

Weis WI & Nelson WJ (2006) Re-solving the cadherin-catenin-actin conundrum.

Journal of Biological Chemistry, 281, 35593-35597.

Elsaesser R & Paysan J (2007) The sense of smell, its signalling pathways, and the

dichotomy of cilia and microvilli in olfactory sensory cells. Bmc Neuroscience, 8.

33.6 Proteingerüste stabilisieren die Erythrocytenmembran

Dubreuil RR (2006) Functional links between membrane transport and the spectrin

cytoskeleton. Journal of Membrane Biology, 211, 151-161.

Mohandas N & Gallagher PG (2008) Red cell membrane: past, present, and future.

Blood, 112, 3939-3948. (PDF)

33.7 Actinfilamente und Mikrotubuli bilden Schienen für Motorproteine

Cross RA (2004) The kinetic mechanism of kinesin, Trends Biochem Sci 29, 300-309

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80

Cheeseman IM & Desai A (2008) Molecular architecture of the kinetochore-

microtubule interface. Nature Reviews Molecular Cell Biology, 9, 33-46.

Hirokawa N, Noda Y, Tanaka Y, & Niwa S (2009) Kinesin superfamily motor proteins

and intracellular transport. Nature Reviews Molecular Cell Biology, 10, 682-696.

33.8 Selectine und CAM-Proteine vermitteln Zelladhäsion

Dalva MB, McClelland AC, & Kayser MS (2007) Cell adhesion molecules: signalling

functions at the synapse. Nature Reviews Neuroscience, 8, 206-220.

Sperandio M (2006) Selectins and glycosyltransferases in leukocyte rolling in vivo.

Febs Journal, 273, 4377-4389.

34 Zellzyklus und programmierter Zelltod

34.1 Cycline und cyclinabhängige Kinasen steuern den eukaryotischen Zellzyklus

Kelly TJ, Brown GW (2000) Regulation of Chromosome Replication, Annu Rev

Biochem 69, 829-80

O´Connell MJ et al (2000) The G2-phase DNA-damage checkpoint, Trends Cell Biol

10, 296-303

Santamaria D & Ortega S (2006) Cyclins and CDKS in development and cancer:

lessons from genetically modified mice. Frontiers in Bioscience, 11, 1164-1188.

Musgrove EA (2006) Cyclins: Roles in mitogenic signaling and oncogenic

transformation. Growth Factors, 24, 13-19.

34.2 Aktivierung von CDK1 startet die Mitose

Hochegger H, Takeda S, & Hunt T (2008) Cyclin-dependent kinases and cell-cycle

transitions: does one fit all? Nature Reviews Molecular Cell Biology, 9, 910-U26.

Malumbres M & Barbacid M (2009) Cell cycle, CDKs and cancer: a changing

paradigm. Nature Reviews Cancer, 9, 153-166.

34.3 CDK4 kontrolliert den Restriktionspunkt in der G1-Phase

Ekholm SV & Reed SI (2000) Regulation of G(1) cyclin dependent kinases in the

mammalian cell cycle. Current Opinion in Cell Biology, 12, 676-684.

Nyberg KA et al (2002) Toward maintaining the genome: DNA damage and

replication checkpoints, Annu Rev Genet 36, 617-656

Graf F, Mosch B, Koehler L, Bergmann R, Wuest F, & Pietzsch J (2010) Cyclin-

Dependent Kinase 4/6 (Cdk4/6) Inhibitors: Perspectives in Cancer Therapy and

Imaging. Mini-Reviews in Medicinal Chemistry, 10, 527-539.

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82

34.4 Der Tumorsuppressor p53 moduliert die Aktivität von CDKs

Vousden KH (2002) Activation of the p53 tumor suppressor protein, Biochim Biophys

Acta 1602, 47-59

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Death and Differentiation, 13, 941-950. (PDF)

Vousden KH & Lane DP (2007) p53 in health and disease. Nature Reviews Molecular

Cell Biology, 8, 275-283.

34.5 Eine enzymatische Kaskade löst den programmierten Zelltod aus

Jiang X, Wang X (2004) Cytochrome c-mediated Apoptosis, Annu Rev Biochem 73,

87-106

Kumar S, Cakouros D (2004) Transkriptional control of the core cell-death machinery,

Trends Biochem Sci 29, 192-199

Roos WP & Kaina B (2006) DNA damage-induced cell death by apoptosis. Trends in

Molecular Medicine, 12, 440-450.

34.6 Caspasen spalten spezifische Funktionsproteine der Zelle

Jiang X, Wang X (2004) Cytochrome c-mediated Apoptosis, Annu Rev Biochem 73,

87-106

Shiozaki E, Yigong S (2004) Caspases, IAPs and Smac/DIABLO, mechanisms from

structural biology, Trends Biochem Sci 29, 486-494

Siegel RM (2006) Caspases at the crossroads of immune-cell life and death. Nature

Reviews Immunology, 6, 308-317.

Lamkanfi M, Festjens N, Declercq W, Vanden Berghe T, & Vandenabeele P (2007)

Caspases in cell survival, proliferation and differentiation. Cell Death and

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35 Molekulare Basis von Krebsentstehung und Krebsbekämpfung

35.1 Tumorzellen haben ungebremstes replikatives Potenzial

Zeng Q & Hong W (2008) The emerging role of the Hippo pathway in cell contact

inhibition, organ size control, and cancer development in mammals. Cancer Cell, 13,

188-192.

DeBerardinis RJ, Lum JJ, Hatzivassiliou G, & Thompson CB (2008) The biology of

cancer: Metabolic reprogramming fuels cell growth and proliferation. Cell Metabolism,

7, 11-20.

35.2 Krebs ist eine genetische Erkrankung

Jain S, Xu R, Prieto VG, Lee P (2010) Molecular classification of soft tissue

sarcomas and its clinical applications. Int J Clin Exp Pathol. 23;3(4):416-28. (PDF)

35.3 Mutagene Agenzien können Krebs auslösen

Sedgwick B, Bates PA, Paik J, Jacobs SC, & Lindahl T (2007) Repair of alkylated

DNA: Recent advances. Dna Repair, 6, 429-442.

Levine AJ (2009) The common mechanisms of transformation by the small DNA

tumor viruses: The inactivation of tumor suppressor gene products: p53. Virology,

384, 285-293.

35.4 Onkogene Zellen können transformieren

Cowling VH & Cole MD (2006) Mechanism of transcriptional activation by the Myc

oncoproteins. Seminars in Cancer Biology, 16, 242-252.

Musgrove EA (2006) Cyclins: Roles in mitogenic signaling and oncogenic

transformation. Growth Factors, 24, 13-19.

Zhao L & Vogt PK (2008) Class I PI3K in oncogenic cellular transformation.

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35.5 Tumorsuppressorgene wachen über die zelluläre Proliferation

Gabellini C, Del Bufalo D, & Zupi G (2006) Involvement of RB gene family in tumor

angiogenesis. Oncogene, 25, 5326-5332.

Riley T, Sontag E, Chen P, & Levine A (2008) Transcriptional control of human p53-

regulated genes. Nature Reviews Molecular Cell Biology, 9, 402-412.

Kim WY & Sharpless NE (2006) The regulation of INK4/ARF in cancer and aging.

Cell, 127, 265-275.

35.6 Wachstumsfaktoren und die Signalproteine Wnt, Notch und Hedgehog steuern basale Zellfunktionen

Bray SJ (2006) Notch signalling: a simple pathway becomes complex. Nature

Reviews Molecular Cell Biology, 7, 678-689.

Clevers H (2006) Wnt/beta-catenin signaling in development and disease. Cell, 127,

469-480.

Zardawi SJ, O'Toole SA, Sutherland RL, & Musgrove EA (2009) Dysregulation of

Hedgehog, Wnt and Notch signalling pathways in breast cancer. Histology and

Histopathology, 24, 385-398.

35.7 p53, TGF- und Rb-Signalwege regulieren Zellteilung und -differenzierung

Bierie B & Moses HL (2006) TGF beta: the molecular Jekyll and Hyde of cancer.

Nature Reviews Cancer, 6, 506-520.

Adams JM & Cory S (2007) The Bcl-2 apoptotic switch in cancer development and

therapy. Oncogene, 26, 1324-1337. (PDF)

35.8 NF-κB- und PI3K-Signalwege wachen über die Apoptose

Baud V & Jacque E (2008) The alternative NF-kappa B activation pathway and

cancer : friend or foe? M S-Medecine Sciences, 24, 1083-1088.

Yuan TL & Cantley LC (2008) PI3K pathway alterations in cancer: variations on a

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35.9 Neue Ansätze in Tumordiagnostik und –therapie basieren auf molekularen Erkenntnissen

Carpi A, Mechanick JI, Saussez S, & Nicolini A (2010) Thyroid Tumor Marker

Genomics and Proteomics: Diagnostic and Clinical Implications. Journal of Cellular

Physiology, 224, 612-619.

Zhang JY & Tan EM (2010) Autoantibodies to tumor-associated antigens as

diagnostic biomarkers in hepatocellular carcinoma and other solid tumors. Expert

Review of Molecular Diagnostics, 10, 321-328.

Giaginis C, Vgenopoulou S, Vielh P, & Theocharis S (2010) MCM proteins as

diagnostic and prognostic tumor markers in the clinical setting. Histology and

Histopathology, 25, 351-370.

35.10 Molekulares Verständnis von Kanzerogenese eröffnet therapeutisches Neuland

Eskens FA & Verweij J (2006) The clinical toxicity profile of vascular endothelial

growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR)

targeting angiogenesis inhibitors; A review. European Journal of Cancer, 42, 3127-

3139.

Pytel D, Sliwinski T, Poplawski T, Ferriola D, & Majsterek I (2009) Tyrosine Kinase

Blockers: New Hope for Successful Cancer Therapy. Anti-Cancer Agents in

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36 Angeborenes und erworbenes Immunsystem

36.1 Das Komplementsystem attackiert bakterielle Invasoren

Kimbrell DA, Beutler B (2001) The evolution and genetics of innate immunity, Nat

Rev Genet 2, 256-267

Girardi G, Bulla R, Salmon JE, & Tedesco F (2006) The complement system in the

pathophysiology of pregnancy. Molecular Immunology, 43, 68-77.

Nonaka M & Kimura A (2006) Genomic view of the evolution of the complement

system. Immunogenetics, 58, 701-713. (PDF)

36.2 Der terminale Komplex stanzt Poren in die Bakterienmembran

Carroll MC (2004) The complement system in regulation of adaptive immunity, Nat

Immunol 5, 981-986

Kemper C & Atkinson JP (2007) T-cell regulation: with complements from innate

immunity. Nature Reviews Immunology, 7, 9-18.

36.3 Das natürliche Immunsystem nutzt Toll-ähnliche Rezeptoren

Janeway CA, Medzhitov R (2002) Innate immune recognition, Annu Rev Immunol 20,

197-216

Takeda K et al (2003) Toll-like receptors, Annu Rev Immunol 21, 335-376

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know. Current Opinion in Immunology, 18, 3-9.

Kawai T & Akira S (2007) Signaling to NF-kappa B by Toll-like receptors. Trends in

Molecular Medicine, 13, 460-469.

36.4 MHC-Proteine präsentieren Antigene auf der Zelloberfläche

Horton R et al (2004) Gen map of the extended human MHC, Nature Rev Gen 5,

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disease: a structural perspective. Nature Reviews Immunology, 6, 271-282.

Yaneva R, Schneeweiss C, Zacharias M, & Springer S (2010) Peptide binding to

MHC class I and II proteins: New avenues from new methods. Molecular

Immunology, 47, 649-657.

36.5 Lymphocyten bilden das Rückgrat des adaptiven Immunsystems

Sprent J, Surh CD (2002) T cell memory, Annu Rev Immunol 20, 551-579

36.6 T-Zellen organisieren die zellvermittelte Immunabwehr

Pitcher LA, van Oers NS (2003) T-cell receptor signal transmission: who gives an

ITAM ?, Trends Immunol 24, 554-560

Laky K, Fleischacker C, & Fowlkes BJ (2006) TCR and notch signaling in CD4 and

CD8 T-cell development. Immunological Reviews, 209, 274-283.

Zhang S, Zhang HJ, & Zhao JD (2009) The role of CD4 T cell help for CD8 CTL

activation. Biochemical and Biophysical Research Communications, 384, 405-408.

36.7 T-Helferzellen stimulieren B-Zellen

Davis MM et al (2003) Dynamics of Cell Surface Molecules During T Cell

Recognition, Annu Rev Biochem 72, 717-742

van der Merwe PA, Davis SJ (2003) Molecular interactions mediating T cell antigen

recognition, Annu Rev Immunol 21, 659-684

Al-Daccac R et al (2004) MHC class II signaling in antigen-presenting cells, Curr

Opin Immunol 16, 108-113

Dinarello CA (2009) Immunological and Inflammatory Functions of the Interleukin-1

Family. Annual Review of Immunology, 27, 519-550.

36.8 Cytotoxische T-Zellen versetzen infizierten Zellen den Todesstoß

Kloetzel PM, Ossendorp F (2004) Proteasome and peptidase function in MHC-class-

I-mediated antigen presentation, Curr Opin Immunol 16, 76-81

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Opinion in Immunology, 19, 354-364.

Zhou F (2010) Expression of Multiple Granzymes by Cytotoxic T Lymphocyte Implies

that They Activate Diverse Apoptotic Pathways in Target Cells. International Reviews

of Immunology, 29, 38-55.

36.9 B-Zellen organisieren die humorale Immunantwort

Martin F & Chan AC (2006) B cell immunobiology in disease: Evolving concepts

from the clinic. Annual Review of Immunology, 24, 467-496.

Lanzavecchia A & Sallusto F (2007) Toll-like receptors and innate immunity in B-cell

activation and antibody responses. Current Opinion in Immunology, 19, 268-274.

36.10 Variable und konstante Domänen bilden die Antikörperketten

Wang W, Singh S, Zeng DL, King K, & Nema S (2007) Antibody structure, instability,

and formulation. Journal of Pharmaceutical Sciences, 96, 1-26.

Chen SW, Van Regenmortel MHV, & Pellequer JL (2009) Structure-Activity

Relationships in Peptide-Antibody Complexes: Implications for Epitope Prediction

and Development of Synthetic Peptide Vaccines. Current Medicinal Chemistry, 16,

953-964.

36.11 Somatische Hypermutation führt zur Affinitätsreifung von B-Zellen

Kinoshita K, Honjo T (2001) Linking class-switch recombination with somatic

hypermutation, Nat Rev Mol Cell Biol 2, 493-503

Odegard VH & Schatz DG (2006) Targeting of somatic hypermutation. Nature

Reviews Immunology, 6, 573-583.

Di Nola JM & Neuberger MS (2007) Molecular mechanisms of antibody somatic

hypermutation. Annual Review of Biochemistry, 76, 1-22.

Peled JU, Kuang FL, Iglesias-Ussel MD, Roa S, Kalis SL, Goodman ME, & Scharff

MD (2008) The biochemistry of somatic hypermutation. Annual Review of

Immunology, 26, 481-511.

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37 Erforschung und Entwicklung neuer Arzeistoffe

37.1 Arzneistoffe binden an definierte Zielmoleküle

Nelson CP & Challiss RAJ (2007) "Phenotypic" pharmacology: The influence of

cellular environment on G protein-coupled receptor antagonist and inverse agonist

pharmacology. Biochemical Pharmacology, 73, 737-751.

Garcia-Lopez MT, Gonzalez-Muniz R, Martin-Martinez M, & Herranz R (2007)

Strategies for design of non peptide CCK1R agonist/antagonist ligands. Current

Topics in Medicinal Chemistry, 7, 1180-1194.

37.2 Arzneistoffe binden mit hoher Affinität an ihr Target

Ota T, Shinotoh H, Fukushi K, Kikuchi T, Sato K, Tanaka N, Shimada H, Hirano S,

Miyoshi M, Arai H, Suhara T, & Irie T (2010) Estimation of Plasma IC50 of Donepezil

for Cerebral Acetylcholinesterase Inhibition in Patients With Alzheimer Disease Using

Positron Emission Tomography. Clinical Neuropharmacology, 33, 74-78.

37.3 Die Analyse von Genomen und Proteomen liefert neue Zielmoleküle

Oh DY, Kim K, Kwon HB, & Seong JY (2006) Cellular and molecular biology of

orphan G protein-coupled receptors. Elsevier Academic Press Inc., San Diego.

Rix U & Superti-Furga G (2009) Target profiling of small molecules by chemical

proteomics. Nature Chemical Biology, 5, 616-624.

Bantscheff M, Scholten A, & Heck AJ (2009) Revealing promiscuous drug-target

interactions by chemical proteomics. Drug Discovery Today, 14, 1021-1029.

37.4 Naturstoffe dienen als Quelle neuer Arzneimittel

Lam KS (2007) New aspects of natural products in drug discovery. Trends in

Microbiology, 15, 279-289.

Molinski TF, Dalisay DS, Lievens SL, & Saludes JP (2009) Drug development from

marine natural products. Nature Reviews Drug Discovery, 8, 69-85.

89

Harvey AL, Clark RL, Mackay SP, & Johnston BF (2010) Current strategies for drug

discovery through natural products. Expert Opinion on Drug Discovery, 5, 559-568.

37.5 Die Durchmusterung von Substanzbibliotheken liefert Arzneistoffkandidaten

Kumar RA & Clark DS (2006) High-throughput screening of biocatalytic activity:

applications in drug discovery. Current Opinion in Chemical Biology, 10, 162-168.

Snowden MA & Green DVS (2008) The impact of diversity-based, high-throughput

screening on drug discovery: "Chance favours the prepared mind". Current Opinion

in Drug Discovery & Development, 11, 553-558.

37.6 Arzneistoffe müssen resorbiert werden und in inakter Form an ihren Wirkort gelangen

de Boer AG & Breimer DD (1997) Hepatic first-pass effect and controlled drug

delivery following rectal administration. Advanced Drug Delivery Reviews, 28, 229-

237.

Chu I & Nomeir AA (2006) Utility of mass spectrometry for in-vitro ADME assays.

Current Drug Metabolism, 7, 467-477.

Ullrich R & Hofrichter M (2007) Enzymatic hydroxylation of aromatic compounds.

Cellular and Molecular Life Sciences, 64, 271-293.

37.7 Arzneistoffe müssen auf toxische Eigenschaften hin geprüft werden

Zunkler BJ (2006) Human ether-a-go-go-related (HERG) gene and ATP-sensitive

potassium channels as targets for adverse drug effects. Pharmacology &

Therapeutics, 112, 12-37.

Chen MX, Helliwell RM, & Clare JJ (2009) In vitro profiling against ion channels

beyond hERG as an early indicator of cardiac risk. Current Opinion in Molecular

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37.8 Monoklonale Antikörper sind wirksame Biotherapeutika

Peterson E, Owens SM, & Henry RL (2006) Monoclonal antibody form and function:

Manufacturing the right antibodies for treating drug abuse. Aaps Journal, 8, E383-

E390.

Mano M & Humblet Y (2008) Drug insight: panitumumab, a human EGFR-targeted

monoclonal antibody with promising clinical activity in colorectal cancer. Nature

Clinical Practice Oncology, 5, 415-425.

Cheson BD & Leonard JP (2008) Drug therapy: Monoclonal antibody therapy for B-

cell non-Hodgkin's lymphoma. New England Journal of Medicine, 359, 613-626.

37.9 Die Arzneimitteltherapie der Zukunft ist personalisiert

van't Veer LJ & Bernards R (2008) Enabling personalized cancer medicine through

analysis of gene-expression patterns. Nature, 452, 564-570.

Zhou SF, Di YM, Chan E, Du YM, Chow VDW, Xue CCL, Lai XS, Wang JC, Li CG,

Tian M, & Duan W (2008) Clinical Pharmacogenetics and Potential Application in

Personalized Medicine. Current Drug Metabolism, 9, 738-784.

Olopade OI, Grushko TA, Nanda R, & Huo DZ (2008) Advances in Breast Cancer:

Pathways to Personalized Medicine. Clinical Cancer Research, 14, 7988-7999.

37.10 Die Entwicklung neuer Arzneistoffe ist langwierig

Adams VR & Leggas M (2007) Sunitinib malate for the treatment of metastatic renal

cell carcinoma and gastrointestinal stromal tumors. Clinical Therapeutics, 29, 1338-

1353.

Luffer-Atlas D (2008) Unique/major human metabolites: Why, how, and when to test

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Teil V Energieumwandlung und Biosynthese

38 Grundprinzipien des Metabolismus

38.1 Biochemische Reaktionen gehorchen den Gesetzen der Thermodynamik

Halle B (2004) Protein hydration dynamics in solution: a critical survey, Philos Trans

Royal Soc 359, 1207-1224 (PDF)

Smith E, Morowitz HJ (2004) Universality in intermediary metabolism, Proc Natl Acad

Sci 101, 13168-13173 (PDF)

Saito N, Ohashi Y, Soga T, & Tomita M (2010) Unveiling cellular biochemical

reactions via metabolomics-driven approaches. Current Opinion in Microbiology, 13,

358-362.

38.2 ATP ist der universelle Energieüberträger

Burnstock G (2006) Historical review: ATP as a neurotransmitter. Trends in

Pharmacological Sciences, 27, 166-176.

38.3 NADH und FADH2 sind die wichtigsten Elektronenüberträger

Lin H (2007) Nicotinamide adenine dinucleotide: beyond a redox coenzyme. Organic

& Biomolecular Chemistry, 5, 2541-2554.

Wos ML & Pollard PC (2009) Cellular nicotinamide adenine dinucleotide (NADH) as

an indicator of bacterial metabolic activity dynamics in activated sludge. Water

Science and Technology, 60, 783-791.

38.4 Coenzym A ist der wichtigste Überträger von Acylgruppen

Engel C, Wierenga R (1996) The diverse world of coenzyme A binding proteins, Curr

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Mitchell GA, Gauthier N, Lesimple A, Wang SP, Mamer O, & Qureshi I (2008)

Hereditary and acquired diseases of acyl-coenzyme A metabolism. Molecular

Genetics and Metabolism, 94, 4-15.

Spry C, Kirk K, & Saliba KJ (2008) Coenzyme A biosynthesis: an antimicrobial drug

target. Fems Microbiology Reviews, 32, 56-106.

38.5 Katabole Wege münden in den Citratzyklus

Owen OE et al (2002) The key role of anaplerosis and cataplerosis for citric acid

cycle function, J Biol Chem 277, 30409-30412 (PDF)

Fernie AR et al (2004) Respiratory metabolism: glycolysis, the TCA cycle and

mitochondrial electron transport, Curr Opin Plant Biol 7, 254-261

38.6 Die Regulation der Stoffwechselprozesse erfolgt multilateral

Jafri MS et al (2001) Cardiac energy metabolism: models of cellular respiration, Annu

Rev Biomed Eng 3, 57-81

Steuer R & Junker BH (2009) Computational Models of Metabolism: Stability and

Regulation in Metabolic Networks. JOHN WILEY & SONS INC, NEW YORK.

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Shimizu K (2009) Toward systematic metabolic engineering based on the analysis of

metabolic regulation by the integration of different levels of information. Biochemical

Engineering Journal, 46, 235-251.

39 Glykolyse – Prototyp eines Stoffwechselwegs

39.1 Der glykolytische Weg läuft über zehn Stationen

Heinrich R et al (1999) The structural design of glycolysis: an evolutionary approach,

Biochem Soc Trans. 27, 294-298

Sarnyai Z & Boros LG (2008) Modeling Networks of Glycolysis, Overall Energy

Metabolism and Drug Metabolism under a Systems Biology Approach. Elsevier

Academic Press Inc., San Diego.

39.2 Die Bildung von Glycerinaldehyd-3-phosphat kostet ATP

Dunaway GA (1983) A review of animal phosphofructokinase isozymes with an

emphasis on their pysiological role, Mol Cell Biochem. 52, 75-91

Wilson JE (2003) Isozymes of mammalian hexokinase: structure, subcellular

localization and metabolic function, J Exp Biol 206, 2049-2057 (PDF)

Kengen SWM, Tuininga JE, Verhees CH, van der Oost J, Stams AJM, & de Vos WM

(2001) ADP-dependent glucokinase and phosphofructokinase from Pyrococcus

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Mathupala SP, Ko YH, & Pedersen PL (2009) Hexokinase-2 bound to mitochondria:

Cancer's stygian link to the "Warburg effect" and a pivotal target for effective therapy.

Seminars in Cancer Biology, 19, 17-24. (PDF)

39.3 Die Oxidation von Glycerinaldehyd-3-phosphat liefert ATP

Berry MD & Boulton AA (2000) Glyceraldehyde-3-phosphate dehydrogenase and

apoptosis. Journal of Neuroscience Research, 60, 150-154.

Chuang DM, Hough C, & Senatorov VV (2005) Glyceraldehyde-3-phosphate

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95

39.4 Die Erzeugung von Pyruvat ist an ATP-Gewinn geknüpft

Sugden MC & Holness MJ (2003) Recent advances in mechanisms regulating

glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs.

American Journal of Physiology-Endocrinology and Metabolism, 284, E855-E862.

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Munoz ME & Ponce E (2003) Pyruvate kinase: current status of regulatory and

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39.5 Die Energiebilanz der Glykolyse ist positiv

van Wijk R & van Solinge WW (2005) The energy-less red blood cell is lost:

erythrocyte enzyme abnormalities of glycolysis. Blood, 106, 4034-4042. (PDF)

39.6 Weitere Kohlenhydrate werden in den glykolytischen Weg eingeschleust

Novelli G & Reichardt JKV (2000) Molecular basis of disorders of human galactose

metabolism: Past, present, and future. Molecular Genetics and Metabolism, 71, 62-

65.

Michels PAM & Rigden DJ (2006) Evolutionary analysis of fructose 2,6-bisphosphate

metabolism. Iubmb Life, 58, 133-141.

39.7 Die Glykolyse wird engmaschig kontrolliert

van de Werve G, Lange A, Newgard C, Mechin MC, Li YZ, & Berteloot A (2000) New

lessons in the regulation of glucose metabolism taught by the glucose 6-phosphatase

system. European Journal of Biochemistry, 267, 1533-1549. (PDF)

Mader A (2003) Glcolysis and oxidative phosphorylation as a function of cytosolic

phosphorylation state and power output of the muscle cell, Eur J Appl Physiol 88,

317-338

Wu CD, Khan SA, & Lange AJ (2005) Regulation of glycolysis - role of insulin.

Experimental Gerontology, 40, 894-899.

40 Citratzyklus – zentrale Drehscheibe des Metabolismus

40.1 Die oxidative Decarboxylierung von Pyruvat liefert Acetyl-CoA

Zhou ZH et al (2001) The remarkable structural and functional organization of

the eucaryotic pyruvate dehydrogenase complexes, PNAS 98, 14802-14807

(PDF)

Roche TE & Hiromasa Y (2007) Pyruvate dehydrogenase kinase regulatory

mechanisms and inhibition in treating diabetes, heart ischemia, and cancer.

Cellular and Molecular Life Sciences, 64, 830-849.

40.2 Der Citratzyklus ist eine geschlossene Folge von neun Einzelreaktionen

Huynen MA et al (1999) Variation and evolution of the citric-acid cycle: a genomic

perspective, Trends Microbiol 7, 281-291

Aoshima M (2007) Novel enzyme reactions related to the tricarboxylic acid cycle:

phylogenetic/functional implications and biotechnological applications. Applied

Microbiology and Biotechnology, 75, 249-255.

40.3 Oxidoreduktasen liefern die Reduktionsäquivalente NADH und FADH2

May SW (1999) Applications of oxidoreductases. Current Opinion in Biotechnology,

10, 370-375.

Cecchini G, Maklashina E, Yankovskaya V, Iverson TM, & Iwata S (2003) Variation in

proton donor/acceptor pathways in succinate : quinone oxidoreductases. Febs

Letters, 545, 31-38.

Jeong JJ et al (2004) Crystal structure of isocitrate dehydrogenase from Aeropyrum

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40.4 Der Citratzyklus bedient katabole und anabole Wege

Gibala MJ et al (2000) Anaplerosis of the citric acid cycle: role in energy metabolism of

heart and skeletal muscle, Acta Physiol Scand 168, 657-665

Owen OE, Kalhan SC, & Hanson RW (2002) The key role of anaplerosis and

cataplerosis for citric acid cycle function. Journal of Biological Chemistry, 277, 30409-

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40.5 Der Citratzyklus unterliegt einer stringenten Kontrolle

Krebs HA (1970) Rate control of the tricarboxylic acid cycle, Adv Enzyme Regul. 8,

335-353

Cozzone AJ & El-Mansi M (2005) Control of isocitrate dehydrogenase catalytic

activity by protein phosphorylation in Escherichia coli. Journal of Molecular

Microbiology and Biotechnology, 9, 132-146.

41 Oxidative Phosphorylierung – Elektronentransport und ATP-

Synthese

41.1 Cytosolisches NADH gelangt über Umwege in die Atmungskette

Minarik P et al (2002) Malate dehydrogenase - - structure and function, Gen Physiol

Biophys 21, 257-265 (PDF)

Li YJ, Dash RK, Kim JY, Saidel GM, & Cabrera ME (2009) Role of NADH/NAD(+)

transport activity and glycogen store on skeletal muscle energy metabolism during

exercise: in silico studies. American Journal of Physiology-Cell Physiology, 296, C25-

C46. (PDF)

41.2 Die oxidative Phosphorylierung verläuft in zwei Pasen

Saraste M (1999) Oxidative phosphorylation at the fin de siecle, Science 283, 1488-

1493

Kerr DS (2010) Treatment of mitochondrial electron transport chain disorders: A

review of clinical trials over the past decade. Molecular Genetics and Metabolism, 99,

246-255.

41.3 Komplex I schleust Elektronen von NADH in die Atmungskette ein

Brandt U (2006) Energy converting NADH : Quinone oxidoreductase (Complex I).

Annual Review of Biochemistry, 75, 69-92.

Lenaz G, Fato R, Formiggini G, & Genova ML (2007) The role of Coenzyme Q in

mitochondrial electron transport. Mitochondrion, 7, S8-S33.

41.4 Verschiedene FAD-abhängige Dehydrogenasen bilden weitere Zuflüsse zur Atmungskette

Scrutton NS, Sutcliffe MJ (2000) Trimethylamine dehydrogenase and electron

transferring flavoprotein, Subcell Biochem. 35, 145-181

Cecchini G (2003) Function and structure of complex II of the respiratory chain, Annu

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Toogood HS, Leys D, & Scrutton NS (2007) Dynamics driving function - new insights

from electron transferring flavoproteins and partner complexes. Febs Journal, 274,

5481-5504.

41.5 Cytochrom c-Reduktase überträgt Elektronen auf Cytochrom c

Hunte C et al (2003) Protonmotive pathways and mechnisms in the cytochrome bc1

complex, FEBS Lett 545, 39-46

Crofts AR (2004) The cytochrome bc1 complex: function in the context of structure,

Annu Rev Physiol, 66, 689-733

Crofts AR, Lhee S, Crofts SB, Cheng J, & Rose S (2006) Proton pumping in the bc(1)

complex: A new gating mechanism that prevents short circuits. Biochimica et

Biophysica Acta-Bioenergetics, 1757, 1019-1034.

Covian R & Trumpower BL (2008) Regulatory interactions in the dimeric cytochrome

bc(1) complex: The advantages of being a twin. Biochimica et Biophysica Acta-

Bioenergetics, 1777, 1079-1091. (PDF)

41.6 Cytochrom c-Oxidase überträgt Elektronen auf molekularen Sauerstoff

Michel H (1999) Cytochrome c oxidase: catalytic cycle and mechanism of proton

pumping - - a discussion, Biochemistry 38, 15129-15140

Richter OM, Ludwig B (2003) Cytochrome c oxidase - - structure, function, and

physiology of a redox driven machine, Rev Physiol Biochem Pharmacol 147, 47-74

Wikstrom M (2004) Cytochrome c oxidase: 25 years of the elusive proton pump,

Biochim Biophys Acta 1655, 241-247

Qin L, Sharpe MA, Garavito RM, & Ferguson-Miller S (2007) Conserved lipid-binding

sites in membrane proteins: a focus on cytochrome c oxidase. Current Opinion in

Structural Biology, 17, 444-450. (PDF)

Diaz F (2010) Cytochrome c oxidase deficiency: Patients and animal models.

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41.7 Elektronentransport und Phosphorylierung sind gekoppelt

Saraste M (1999) Oxidative phosphorylation at the fin de siecle, Science 283, 1488-

1493

Huttemann M, Lee I, Pecinova A, Pecina P, Przyklenk K, & Doan JW (2008)

Regulation of oxidative phosphorylation, the mitochondrial membrane potential, and

their role in human disease. Journal of Bioenergetics and Biomembranes, 40, 445-

456.

41.8 Ein Nano-Rotationsmotor synthetisiert ATP

Boyer PD (2002) Catalytic occupancy during ATP synthase catalysis, FEBS Lett 512,

29-32

Weber J, Senior AE (2003) ATP synthesis driven by proton transport in F1F0-ATP

synthase, FEBS Lett 545, 61-70

Nakamoto RK, Scanlon JAB, & Al-Shawi MK (2008) The rotary mechanism of the

ATP synthase. Archives of Biochemistry and Biophysics, 476, 43-50. (PDF)

von Ballmoos C, Cook GM, & Dimroth P (2008) Unique rotary ATP synthase and its

biological diversity. Annual Review of Biophysics, 37, 43-64.

41.9 Eine Translokase lässt Nucleotide über Membranen fließen

Palmieri L et al (2000) Yeast mitochondrial carriers: bacterial expression, biochemical

identification and metabolic significance, J Bioenerg Biomembr 32, 67-77

Halestrap AP, Brennerb C (2003) The adenine nucleotide translocase: a central

component of the mitochondrial permeability transition pore and key player in cell

death, Curr Med Chem 10, 1507-1525

Dorner A & Schultheiss HP (2007) Adenine nucleotide translocase in the focus of

cardiovascular diseases. Trends in Cardiovascular Medicine, 17, 284-290.

41.10 Entkoppler verursachen einen Kurzschluss der Protonenbatterie

Kadenbach B (2003) Intrinsic and extrinsic uncoupling of oxidative phosphorylation,

Biochim Biophys Acta 1604, 77-94

Cannon B und Nedergaard J (2004) Brown adipose tissue: function and physiological

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100

101

Kovacic P, Pozos RS, Somanathan R, Shangari N, & O'Brien PJ (2005) Mechanism

of mitochondrial uncouplers, inhibitors, and toxins: Focus on electron transfer, free

radicals, and structure-activity relationships. Current Medicinal Chemistry, 12, 2601-

2623.

41.11 Die Verbrennung von 1 Mol Glucose erzeugt bis zu 30 Mol ATP

Rigoulet M, Leverve X, Fontaine E, Ouhabi R, & Guerin B (1998) Quantitative

analysis of some mechanisms affecting the yield of oxidative phosphorylation:

Dependence upon both fluxes and forces. Molecular and Cellular Biochemistry, 184,

35-52.

42 Pentosephosphatweg- ein adaptives Stoffwechselmodul

42.1 Der Pentosephosphatweg läuft in zwei Phasen ab

Kruger NJ, von Schaewen A (2003) The oxidative pentose phosphate pathway:

structure and organisation,Curr Opin Plant Biol 6, 236-46

Huck JH et al (2003) Profiling of pentose phosphate pathway intermediates in blood

spots by tandem mass spectrometry: application to transaldolase deficiency, Clin

Chem 49, 1375-80 (PDF)

Gupte SA (2008) Glucose-6-phosphate dehydrogenase: A novel therapeutic target in

cardiovascular diseases. Current Opinion in Investigational Drugs, 9, 993-1000.

Bolanos JP, Almeida A, & Moncada S (2010) Glycolysis: a bioenergetic or a survival

pathway? Trends in Biochemical Sciences, 35, 145-149.

42.2 Die oxidative Phase liefert NADPH und Ribulose-5-phosphat

Duffieux F et al (2000) Molecular characterization of the first two enzymes of the

pentose-phosphate pathway of Trypanosoma brucei. Clucose-6-phosphate

dehydrogenase and 6-phosphogluconolactonase, J Biol Chem 275, 27559-65 (PDF)

Ho HY, Cheng ML, & Chiu DTY (2007) Glucose-6-phosphate dehydrogenase - from

oxidative stress to cellular functions and degenerative diseases. Redox Report, 12,

109-118.

Cappellini MD & Fiorelli G (2008) Gluclose-6-phosphate dehydrogenase deficiency.

Lancet, 371, 64-74.

42.3 Die nichtoxidative Phase interkonvertiert Kohlenhydrate

Kochetov GA (2001) Functional flexibility of the transketolase molecule, Biochemistry

(Mosc.) 66, 1077-85 (PDF)

Zhao J & Zhong CJ (2009) A review on research progress of transketolase. Neurosci

Bull, 25.

Samland AK & Sprenger GA (2009) Transaldolase: From biochemistry to human

disease. International Journal of Biochemistry & Cell Biology, 41, 1482-1494.

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42.4 Der Pentosephosphatweg dient wechselnden zellulären Bedürfnissen

Siems WG et al (2000) Erythrocyte free radical and energy metabolism, Clin Nephrol

53(1 Suppl), 9-17

Tozzi MG, Camici M, Mascia L, Sgarrella F, & Ipata PL (2006) Pentose phosphates

in nucleoside interconversion and catabolism. Febs Journal, 273, 1089-1101.

43 Gluconeogenese und Cori-Zyklus

43.1 Die Gluconeogenese läuft über elf enzymatische Stationen

Hers HG, Hue L (1983) Gluconeogenesis and related aspects of glycolysis, Annu

Rev Biochem 52, 617-53

Nuttall FQ, Ngo A, & Gannon MC (2008) Regulation of hepatic glucose production

and the role of gluconeogenesis in humans: is the rate of gluconeogenesis constant?

Diabetes-Metabolism Research and Reviews, 24, 438-458.

43.2 Eine transiente Carboxylierung führt über Oxalacetat zum Phosphoenolpyruvat

Delbaere LT et al (2004) Structure/function studies of phosphoryl transfer by

phosphoenolpyruvate carboxykinase, Biochim Biophys Acta 1697, 271-8

Jitrapakdee S, St Maurice M, Rayment I, Cleland WW, Wallace JC, & Attwood PV

(2008) Structure, mechanism and regulation of pyruvate carboxylase. Biochemical

Journal, 413, 369-387. (PDF)

43.3 Zwei Phosphatasen sind Schlüsselenzyme der Gluconeogenese

Foster JD, Nordlie RC (2002) The biochemistry and molecular biology of the glucose-

6-phosphatase system, Exp Biol Med (Maywood) 227, 601-8 (PDF)

van Sschaftingen E, Gerin I (2002) The glucose-6-phosphatase system, Biochem J

362, 513-32 (PDF)

van Poelje PD, Dang Q, & Erion MD (2007) Discovery of fructose-1,6-

bisphosphatase inhibitors for the treatment of type 2 diabetes. Current Opinion in

Drug Discovery & Development, 10, 430-437.

Hutton JC & O'Brien RM (2009) Glucose-6-phosphatase Catalytic Subunit Gene

Family. Journal of Biological Chemistry, 284, 29241-29245.

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105

43.4 Glykolyse und Gluconeogenese werden reziprok reguliert

Tirone TA, Brunicardi FC (2001) Overview of glucose regulation, World J Surg 25,

461-7

Boden G (2003) Effects of free fatty acids on gluconeogenesis and glycogenolysis,

Life Sci 72, 977-88

Heijboer AC, Pijl H, Van den Hoek AM, Havekes LM, Romijn JA, & Corssmit EPM

(2006) Gut-brain axis: Regulation of glucose metabolism. Journal of

Neuroendocrinology, 18, 883-894.

Yalcin A, Telang S, Clem B, & Chesney J (2009) Regulation of glucose metabolism

by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases in cancer. Experimental

and Molecular Pathology, 86, 174-179.

43.5 Der Cori-Zyklus verbindet muskuläre Glykolyse und hepatische Gluconeogenese

Katz J, Tayek JA (1999) Recycling of glucose and determination of the Cori Cycle

and gluconeogenesis, Am J Physiol 277, E401-7 (PDF)

Granchi C, Bertini S, Macchia M, & Minutolo F (2010) Inhibitors of Lactate

Dehydrogenase Isoforms and their Therapeutic Potentials. Current Medicinal

Chemistry, 17, 672-697.

44 Biosynthese und Abbau von Glykogen

44.1 Glykogen ist ein verzweigtes Glucosepolymer

Roach PJ (2002) Glycogen and its metabolism, Curr Mol Med 2, 101-20

Shearer J, Graham TE (2002) New perspectives on the storage and organization of

muscle glycogen, Can J Appl Physiol 27, 179-203

Ozen H (2007) Glycogen storage diseases: New perspectives. World Journal of

Gastroenterology, 13, 2541-2553. (PDF)

44.2 Die Glykogensynthese läuft über vier enzymatische Stationen

Melendez R, Melendez-Hevia E and Cascante M (1997) How did glycogen structure

evolve to satisfy the requirement for rapid mobilzation of glucose? A problem of

physical constraints in structure building, J Mol Evol 45, 446-55

Ballicora MA, Iglesias AA, & Preiss J (2003) ADP-glucose pyrophosphorylase, a

regulatory enzyme for bacterial glycogen synthesis. Microbiology and Molecular

Biology Reviews, 67, 213-25. (PDF)

Agius L (2008) Glucokinase and molecular aspects of liver glycogen metabolism.

Biochemical Journal, 414, 1-18.

44.3 Glykogen-Synthase ist das Schlüsselenzym beim Aufbau von Glykogen

Lomako J et al (2004) Glycogenin: the primer for mammalian and yeast glycogen

synthesis, Biochim Biophys Acta 1673, 45-55

Weinstein DA, Correia CE, Saunders AC, & Wolfsdorf JI (2006) Hepatic glycogen

synthase deficiency: An infrequently recognized cause of ketotic hypoglycemia.

Molecular Genetics and Metabolism, 87, 284-288. (PDF)

Graham TE, Yuan Z, Hill AK, & Wilson RJ (2010) The regulation of muscle glycogen:

the granule and its proteins. Acta Physiologica, 199, 489-498.

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44.4 Eine Transglykosylase verzweigt wachsende Glykogenketten

Abad MC et al (2002) The X-ray crystallographic structure of Escherichia coli

branching enzyme, J Biol Chem 277, 42164-70 (PDF)

Ostash B & Walker S (2005) Bacterial transglycosylase inhibitors. Current Opinion in

Chemical Biology, 9, 459-466.

44.5 Die Glykogenolyse umfasst fünf enzymatische Stationen

Bollen M et al (1998) Specific features of glycogen metabolism in the liver, Biochem

J, 336, 19-31 (PDF)

Greenberg CC, Jurczak MJ, Danos AM, & Brady MJ (2006) Glycogen branches out:

new perspectives on the role of glycogen metabolism in the integration of metabolic

pathways. American Journal of Physiology-Endocrinology and Metabolism, 291, E1-

E8. (PDF)

44.6 Glykogen-Phosphorylase ist das Schlüsselenzym der Glykogenolyse

Livanova NB et al (2002) Pyridoxal 5’-phosphate as a catalytic and conformational

cofactor of muscle glycogen phosphorylase B, Biochemistry (Mosc) 67, 1089-98

(PDF)

Somsak L, Czifrak K, Toth M, Bokor E, Chrysina ED, Alexacou KM, Hayes JM,

Tiraidis C, Lazoura E, Leonidas DD, Zographos SE, & Oikonomakos NG (2008) New

Inhibitors of Glycogen Phosphorylase as Potential Antidiabetic Agents. Current

Medicinal Chemistry, 15, 2933-2983.

Richard JP, Amyes TL, Crugeiras J, & Rios A (2009) Pyridoxal 5 '-phosphate:

electrophilic catalyst extraordinaire. Current Opinion in Chemical Biology, 13, 475-

483.

44.7 Ein bifunktionelles Enzym entzweigt Glykogen

Nakayama A et al (2001) Identification of the catalytic residues of bifunctional

glycogen debranching enzyme, Biol Chem 276, 28824-8 (PDF)

Narahara E et al (2001) Glycogen debranching enzyme in bovine brain, Biochem

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107

108

Lees SJ et al (2004) Glycogen debranching enzyme is associated with rat skeletal

muscle sarcoplasmic reticulum, Acta Physiol Scand 181, 239-45

44.8 Störungen des Glykogenabbaus führen zu Speicherkrankheiten

Chen YT et al (2002) Prenatal diagnosis in glycogen storage diseases, Prenat Diagn

22, 357-9

Wolfsdorf JI, Weinstein DA (2003) Glycogen storage diseases, Rev Endocr Metab

Disord 4, 95-102

Koeberl DD, Kishnani PS, Bali D, & Chen YT (2009) Emerging therapies for glycogen

storage disease type I. Trends in Endocrinology and Metabolism, 20, 252-258.

44.9 Hormonelle Signale steuern den Glykogenstoffwechsel

Yeaman SJ et al (2001) Regulation of glycogen synthesis in human muscle cells,

Biochem Soc Trans 29, 537-41

Klover PJ, Mooney RA (2004) Hepatocytes: critical for glucose homeostasis, Int J

Biochem Cell Biol 36, 753-8

Holst JJ (2007) The physiology of glucagon-like peptide 1. Physiological Reviews, 87,

1409-1439. (PDF)

Wasserman DH (2009) Four grams of glucose. American Journal of Physiology-

Endocrinology and Metabolism, 296, E11-E21. (PDF)

45 Fettsäuresynthese und β-Oxidation

45.1 Die Struktur der Fettsäuren bestimmt ihre Eigenschaften

Kaneko F et al (1998) Diversity in the fatty-acid conformation and chain packing of

cis-unsaturated lipids, Curr Opin Struct Biol 8, 417-25

Griel AE & Kris-Etherton PM (2006) Beyond saturated fat: The importance of the

dietary fatty acid profile on cardiovascular disease. Nutrition Reviews, 64, 257-262.

45.2 Lipasen hydrolysieren Triacylglycerine zu freien Fettsäuren

Yeaman SJ (2004) Hormone-sensitive lipase – new roles for an old enzyme,

Biochem J 379, 11-22 (PDF)

Cilingiroglu M, Ballantyne C (2004) Endothelial lipase and cholesterol metabolism,

Curr Atheroscler Rep 6, 126-30

Zimmermann R, Lass A, Haemmerle G, & Zechner R (2009) Fate of fat: The role of

adipose triglyceride lipase in lipolysis. Biochimica et Biophysica Acta-Molecular and

Cell Biology of Lipids, 1791, 494-500.

45.3 Acylcarnitin ist die Transportform der Fettsäuren

Eaton S (2002) Control of mitochondrial beta-oxidation flux, Prog Lipid Res 41, 197-

239

Ramsay RR, Naismith JH (2003) A snapshot of carnitine acetyltransferase, Trends

Biochem Sci 28, 343-6

Stephens FB, Constantin-Teodosiu D, & Greenhaff PL (2007) New insights

concerning the role of carnitine in the regulation of fuel metabolism in skeletal

muscle. Journal of Physiology-London, 581, 431-444. (PDF)

45.4 Die β-Oxidation spaltet sukzessive C2-Einheiten von Fettsäuren ab

Ghisla S (2004) Beta-oxidation of fatty acids. A century of discovery, Eur J Biochem

271, 459-61

Bartlett K, Eaton S (2004) Mitochondrial beta-oxidation, Eur J Biochem 271, 462-9

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Zhang LY, Keung W, Samokhvalov V, Wang W, & Lopaschuk GD (2010) Role of fatty

acid uptake and fatty acid beta-oxidation in mediating insulin resistance in heart and

skeletal muscle. Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids,

1801, 1-22.

45.5 Zwei zusätzliche Enzyme erlauben den Abbau ungesättigter Fettsäuren

Novikov DK et al (1999) Enzymology of beta-oxidation of (poly)unsaturated fatty

acids, Adv Exp Med Biol 466, 301-9

Poirier Y, Antonenkov VD, Glumoff T, & Hiltunen JK (2006) Peroxisomal beta-

oxidation - A metabolic pathway with multiple functions. Biochimica et Biophysica

Acta-Molecular Cell Research, 1763, 1413-1426.

45.6 Bei einem Überangebot an Acetyl-CoA entstehen Ketonkörper

Fukao T et al (2004) Pathways and control of ketone body metabolism: on the fringe

of lipid biochemistry, Prostaglandins Leukot Essent Fatty Acids 70, 243-51

Maalouf M, Rho JM, & Mattson MP (2009) The neuroprotective properties of calorie

restriction, the ketogenic diet, and ketone bodies. Brain Research Reviews, 59, 293-

315. (PDF)

45.7 Die Fettsäuresynthese ist keine einfache Umkehrung der β-Oxidation

Munday MR (2002) Regulation of mammalian acetyl-CoA carboxylase, Biochem Soc

Trans 30, 1059-64

Smith S et al (2003) Structural and functional organization of the animal fatty acid

synthase, Prog Lipid Res 42, 289-317

Menendez JA & Lupu R (2007) Fatty acid synthase and the lipogenic phenotype in

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111

45.8 Fettsäure-Synthase ist ein multifunktionelles Enzym

Smith S (1994) The animal fatty acid synthase: one gene, one polypeptide, seven

enzymes, FASEB J 8, 1248-59 (PDF)

Smith S et al (2003) Structural and functional organization of the animal fatty acid

synthase, Prog Lipid Res 42, 289-317

45.9 Fettsäuren entstehen durch multiple Kondensation von C2-Einheiten

Wakil SJ (1989) Fatty acid synthase, aproficient multifunctional enzyme,

Biochemistry 28, 4523-30

Kremer L, Dover LG, Carrere S, Nampoothiri KM, Lesjean S, Brown AK, Brennan PJ,

Minnikin DE, Locht C, & Besra GS (2002) Mycolic acid biosynthesis and enzymic

characterization of the beta-ketoacyl-ACP synthase A-condensing enzyme from

Mycobacterium tuberculosis. Biochemical Journal, 364, 423-430. (PDF)

45.10 Im Cytosol entstehen längerkettige und ungesättigte Fettsäuren

Ntambi JM, Miyazaki M (2003) Recent insights into stearoyl-CoA desaturase-1, Curr

Opin Lipidol 14, 255-61

Leonard AE et al (2004) Elongation of long-chain fatty acids, Prog Lipid Res 43, 36-

54

Tehlivets O, Scheuringer K, & Kohlwein SD (2007) Fatty acid synthesis and

elongation in yeast. Biochimica et Biophysica Acta-Molecular and Cell Biology of

Lipids, 1771, 255-270.

45.11 Arachidonsäure ist die Vorstufe von Prostaglandinen und Thromboxanen

Ruan KH (2004) Advance in understanding the biosynthesis of prostacyclin and

thromboxane A2 in the endoplasmic reticulum membrane via the cyclooxygenase

pathway, Mini Rev Med Chem 4, 639-47

Harizi H, Corcuff JB, & Gualde N (2008) Arachidonic-acid-derived eicosanoids: roles

in biology and immunopathology. Trends in Molecular Medicine, 14, 461-469.

46 Biosynthese von Cholesterin, Steroiden und Membranlipiden

46.1 Cholesterin entsteht durch multiple Kondensation von Acetyl-CoA

Olivier LM, Krisans SK (2000) Peroxisomal protein targeting and identification of

peroxisomal targeting signals in cholesterol biosynthetic enzymes, Biochim Biophys

Acta 1529, 89-102

Santosa S, Varady KA, AbuMweis S, & Jones PJ (2007) Physiological and

therapeutic factors affecting cholesterol metabolism: Does a reciprocal relationship

between cholesterol absorption and synthesis really exist? Life Sciences, 80, 505-

514.

46.2 Eine komplexe Reaktionsabfolge führt vom Isopentenylpyrophosphat zum Cholesterin

Wang KC, Ohnuma S (2000) Isoprenyl diphosphate synthases, Biochim Biophys

Acta 1529, 33-48

DeBose-Boyd RA (2008) Feedback regulation of cholesterol synthesis: sterol-

accelerated ubiquitination and degradation of HMG CoA reductase. Cell Research,

18, 609-619. (PDF)

46.3 Lipoproteine steuern Transport und Verwertung von Cholesterin

Kruth HS (2001) Lipoprotein cholesterol and atherosclerosis, Curr Mol Med 1, 633-53

Schaefer EJ (2002) Lipoproteins, nutrition, and heart disease, Am J Clin Nutr 75,

191-212 (PDF)

Davidson WS & Thompson TB (2007) The structure of apolipoprotein A-I in high

density lipoproteins. Journal of Biological Chemistry, 282, 22249-22253. (PDF)

46.4 LDL wird über rezeptorvermittelte Endocytose internalisiert

Schneider WJ, Nimpf J (2003) LDL receptor relatives at the crossroad of endocytosis

and signaling, Cell Mol Life Sci 60, 892-903

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Blacklow SC (2007) Versatility in ligand recognition by LDL receptor family proteins:

advances and frontiers. Current Opinion in Structural Biology, 17, 419-426. (PDF)

46.5 Störungen der Cholesterinverwertung führen zu Hyperlipidämien

Soutar AK et al (2003) Genetics, clinical phenotype, and molecular cell biology of

autosomal recessive hypercholesterolemia, Arterioscler Thromb Vasc Biol 23, 1963-

70 (PDF)

Gotto AM Jr (2003) Treating hypercholesterolemia: looking forward, Clin Cardiol 26(1

Suppl 1), I21-8

Smit JW, Diamant M (2004) Genetically defined hyperlipidemia, Pharmacogenomics

5, 295-304

46.6 Gallensäuren und Steroidhormone entstehen aus Cholesterin

Russell DW (2003) The enzymes, regulation, and genetics of bile acid synthesis,

Annu Rev Biochem 72, 137-74

Espenshade PJ & Hughes AL (2007) Regulation of sterol synthesis in eukaryotes.

Annual Review of Genetics, 41, 401-427.

Norlin M & Wikvall K (2007) Enzymes in the conversion of cholesterol into bile acids.

Current Molecular Medicine, 7, 199-218.

46.7 Gallensäuren sind natürliche Detergenzien

Thomson AB et al (1993) Lipid absorption: passing through the unstirred layers,

brushborder membrane, and beyond, Ca J Physiol Pharmacol 71, 531-55

Houten SM, Watanabe M, & Auwerx J (2006) Endocrine functions of bile acids. Embo

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46.8 Progesteron ist die gemeinsame Vorstufe aller Steroidhormone

Edwards PA, Ericsson J (1999) Sterols and isoprenoids: signaling molecules derived

from the cholesterol biosynthetic pathway, Annu Rev Biochem 68, 157-85

Patel FA, Funder JW, & Challis JRG (2003) Mechanism of cortisol/progesterone

antagonism in the regulation of 15-hydroxyprostaglandin dehydrogenase activity and

113

114

messenger ribonucleic acid levels in human chorion and placental trophoblast cells at

term. Journal of Clinical Endocrinology & Metabolism, 88, 2922-2933. (PDF)

46.9 Phosphatidsäure ist die gemeinsame Vorstufe aller Phosphoglyceride

Vance JE, Vance DE (2004) Phospholipid biosynthesis in mammalian cells, Biochem

Cell Biol 82, 113-28

Kooijman EE & Burger KNJ (2009) Biophysics and function of phosphatidic acid: A

molecular perspective. Biochimica et Biophysica Acta-Molecular and Cell Biology of

Lipids, 1791, 881-888.

Carman GM & Han GS (2009) Phosphatidic Acid Phosphatase, a Key Enzyme in the

Regulation of Lipid Synthesis. Journal of Biological Chemistry, 284, 2593-2597.

(PDF)

46.10 Ceramid ist die Vorstufe aller Sphingolipide

Merrill AH Jr (2002) De novo sphingolipid biosynthesis: a necessary, but dangerous,

pathway, J Biol Chem 277, 25843-6 (PDF)

Hanada K (2003) Serine palmitoyltransferase, a key enzyme of shpingolipid

metabolism, Biochim Biophys Acta 1632, 16-30

Grassme H, Riethmuller J, & Gulbins E (2007) Biological aspects of ceramide-

enriched membrane domains. Progress in Lipid Research, 46, 161-170.

46.11 Ein gestörter Sphingolipidabbau führt zu Lipidspeicherkrankheiten

Butters TD et al (2003) New therapeutics for the treatment of glycosphingolipid

lysosomal storage diseases, Adv Exp Med Biol 535, 219-26

Zhang X, Kiechle FL (2004) eview: Glycosphingolipids in health and disease, Ann

Clin Lab 34, 3-13

Sillence DJ (2007) New insights into glycosphingolipid functions - Storage, lipid rafts,

and translocators. Elsevier Academic Press Inc., San Diego.

47 Abbau von Aminosäuren und Harnstoffzyklus

47.1 Transaminierungen entfernen die α-Aminogruppe der Aminosäuren

Christen P, Mehta PK (2001) From cofactor to enzymes. The molecular evolution of

pyridoxal-5’-phosphate-dependent enzymes, Chem Rec 1, 436-47

Burns KA, Kurian S, & Burke CC (2007) Evaluating patients with mildly elevated

transaminase levels. Clin J Oncol Nurs, 11.

47.2 Der Harnstoffzyklus entsorgt freie Ammoniumionen unter Energieaufwand

Morris SM Jr (2002) Regulation of enzymes of the urea cycle and arginine

metabolism, Annu Rev Nutr 22, 87-105

Husson A et al (2003) Argininosuccinate synthetase from the urea cycle to the

citrulline-NO cycle, Eur J Biochem 270, 1887-99 (PDF)

Deignan JL, Cederbaum SD, & Grody WW (2008) Contrasting features of urea cycle

disorders in human patients and knockout mouse models. Molecular Genetics and

Metabolism, 93, 7-14. (PDF)

47.3 Das Kohlenstoffgerüst der Aminosäuren gelangt in den Citratzyklus

Owen OE et al (2002) The key role of anaplerosis and cataplerosis for citric acid

cycle function, Biol Chem 277, 30409-12 (PDF)

Newsholme P, Brennan L, Rubi B, & Maechler P (2005) New insights into amino acid

metabolism, beta-cell function and diabetes. Clinical Science, 108, 185-194.

47.4 Hauptprodukt der C2- und C3-Familien sind Acetyl-CoA bzw. Pyruvat

Yudkoff M (1997) Brain metabolism of branched-chain amino acids, Glia 21, 92-8

Layman DK (2002) Role of leucine in protein metabolism during exercise and

recovery, Can J Appl Physiol 27, 646-63

115

116

47.5 Oxalacetat, Succinat und Fumarat sind Intermediate der C4-Familie

Blau N, Erlandsen H (2004) The metabolic and molecular bases of

tetrahydrobiopterinresponsive phenylalanine hydroxylase deficiency, Mol Genet

Metab 82, 101-11

Schnell JR et al (2004) Structure, dynamics, and catalytic function of dihydrofolate

reductase, Annu Rev Biophys Biomol Struct 33, 119-40

Bolstad DB, Bolstad ESD, Wright DL, & Anderson AC (2008) Dihydrofolate reductase

inhibitors: developments in antiparasitic chemotherapy. Expert Opinion on

Therapeutic Patents, 18, 143-157.

47.6 Verzweigtketten-Dehydrogenase baut Intermediate der C4-S-Familie

ab

Banerjee R, Ragsdale SW (2003) The many faces of vitamin B12: catalysis by

cobalamin-dependent enzymes, Annu Rev Biochem 72, 209-47

Harris RA et al (2004) Mechanisms responsible for regulation of branched-chain

amino acid catabolism, Biochem Biophys Res Commun 313, 391-6

Binder S, Knill T, & Schuster J (2007) Branched-chain amino acid metabolism in

higher plants. Physiologia Plantarum, 129, 68-78.

47.7 α-Ketoglutarat ist Sammelpunkt beim Abbau der C5-Familie

Curthoys NP, Watford M (1995) Regulation of glutaminase activity and glutamine

metabolism, Annu Rev Nutr 15, 133-59

Haussinger D & Schliess F (2007) Glutamine metabolism and signaling in the liver.

Frontiers in Bioscience, 12, 371-391.

48 Biosynthese von Aminosäuren und Häm

48.1 Die α-Aminogruppe entstammt molekularem Stickstoff

Suarez I et al (2002) Glutamine synthetase in brain: effect of ammonia, Neurochem

Int 41, 123-42

Stanley CA (2004) Hyperinsulinism/hyperammonemia syndrome: insights into the

regulatory role of glutamate dehydrogenase in ammonia metabolism, Mol Genet

Metab 81 Suppl 1, 45-51

48.2 Das Kohlenstoffgerüst der Aminosäuren stammt aus Intermediaten des Stoffwechsels

Umbarger HE (1978) Amino acid biosynthesis and its regulation, Annu Rev Biochem

47, 532-606

Curien G, Biou V, Mas-Droux C, Robert-Genthon M, Ferrer JL, & Dumas R (2008)

Amino acid biosynthesis: New architectures in allosteric enzymes. Plant Physiology

and Biochemistry, 46, 325-339.

48.3 Einfache Reaktionen liefern acht nichtessenzielle Aminosäuren

Maden BE (2000) Tetrahydrofolate and tetrahydromethanopterin compared:

functionally distinct carriers in C1 metabolism, Biochem J 350, 609-29 (PDF)

Selhub J (2002) Folate, vitamin B12 and vitamin B6 and one carbon metabolism,

Nutr Health Aging 6, 39-42

Ragsdale SW (2008) Catalysis of Methyl Group Transfers Involving Tetrahydrofolate

and B-12. Elsevier Academic Press Inc., San Diego.

48.4 3-Phosphoglycerat ist Vorstufe für Serin, Glycin und Cystein

Fontecave M et al (2004) S-adenosylmethionine: nothing goes to waste, Trends

Biochem Sci 29, 243-9

Stipanuk MH (2004) Sulfur amino acid metabolism: pathways for production and

removal of homocysteine and cysteine, Annu Rev Nutr 24, 539-77

117

118

Wang SC & Frey PA (2007) S-adenosylmethionine as an oxidant: the radical SAM

superfamily. Trends in Biochemical Sciences, 32, 101-110.

48.5 Aminosäuren sind Vorstufen von Hormonen und Neurotransmittern

Barrenetxe J et al (2004) Physiological and metabolic functions of melatonin, Physiol

Biochem 60, 61-72

Grillo MA, Colombatto S (2004) Metabolism and function in animal tissues of

agmatine, a biogenic amine formed from arginine, Amino Acids 26, 3-8

Kvetnansky R, Sabban EL, & Palkovits M (2009) Catecholaminergic Systems in

Stress: Structural and Molecular Genetic Approaches. Physiological Reviews, 89, 535-606. (PDF)

48.6 Porphyrine entstehen aus Glycin und Succinyl-CoA

Fujita H (1997) Molecular mechanism of heme biosynthesis, Tohoku J Exp Med 183,

83-99 (PDF)

Schultz IJ, Chen C, Paw BH, & Hamza I (2010) Iron and porphyrin trafficking in heme

biogenesis. J Biol Chem, 285.

48.7 Der Abbau von Häm erzeugt Bilirubin und Biliverdin

Kapitulnik J (2004) Bilirubin: an endogenous product of heme degradation with both

cytotoxic and cytoprotective properties, Mol Pharmacol 66, 773-9 (PDF)

Shibahara S et al (2002) Heme degradation and human disease: diversity is the soul

of life, Antioxid Redox Signal 4, 593-602

Vitek L & Ostrow JD (2009) Bilirubin Chemistry and Metabolism; Harmful and

Protective Aspects. Current Pharmaceutical Design, 15, 2869-2883.

49 Bereitstellung und Verwertung von Nucleotiden

49.1 Die Neusynthese von Purinnucleotiden läuft über zehn Teilreaktionen

Zalkin H, Dixon JE (1992) De novo purine nucleotide biosynthesis, Prog Nucleic Acid

Res Mol Biol 42, 259-87

Tatibana M et al (1995) Mammalian phosphoribosyl-pyrophosphate synthetase, Adv

Enzyme Regul 35, 229-49

Zimmer HG (1998) Significance of the 5-phosphoribosyl-1-pyrophosphate pool for

cardiac purine and pyrimidine nucleotide synthesis: studies with ribose, adenine,

inosine, and orotic acid in rats, Cardiovasc Drugs Ther 12 Suppl2, 179-87

49.2 Der zweite Teil des Purinringsystems wird schrittweise aufgebaut

Maden BE (2000) Tetrahydrofolate and terahydromethanopterin compared:

functionally distinct carriers in C1 metabolism, Biochem J 350, 609-29 (PDF)

Ashihara H, Sano H, & Crozier A (2008) Caffeine and related purine alkaloids:

Biosynthesis, catabolism, function and genetic engineering. Phytochemistry, 69, 841-

856.

49.3 Die Biosynthese von Purinnucleotiden wird engmaschig kontrolliert

Moriwaki Y et al (1999) Enzymes involved in purine metabolism – a review of

histochemical localization and functional implications, Histol Histopathol 14, 1321-40

Downie MJ, Kirk K, & Ben Mamoun C (2008) Purine salvage pathways in the

intraerythrocytic malaria parasite Plasmodium falciparum. Eukaryotic Cell, 7, 1231-

1237. (PDF)

49.4 Carbamoylphosphat, Aspartat und PRPP sind Bausteine bei der Pyrimidinbiosynthese

Evans DR, Guy HI (2004) Mammalian pyrimidine biosynthesis: fresh insights into an

ancient pathway, J Biol Chem 279, 33035-8 (PDF)

119

120

Zrenner R, Stitt M, Sonnewald U, & Boldt R (2006) Pyrimidine and purine

biosynthesis and degradation in plants. Annual Review of Plant Biology, 57, 805-836.

49.5 Nucleosidtriphosphate entstehen unter Verbrauch von ATP

Ishikawa N et al (2003) Molecular evolution of nucleoside diphosphate kinase genes:

conserved core structures and multiple-layered regulatory regions, J Bioenerg

Biomembr 35, 5-6

Yegutkin GG (2008) Nucleotide- and nucleoside-converting ectoenzymes: Important

modulators of purinergic signalling cascade. Biochimica et Biophysica Acta-Molecular

Cell Research, 1783, 673-694.

49.6 Desoxyribonucleotide entstehen aus Nucleosiddiphosphaten

Eklund H et al (2001) Structure and function of the radical enzyme ribonucleotide

reductase, Prog Biophys Mol Biol 77, 177-268

Stubbe J et al (2003) Radical initiation in the class I ribonucleotide reductase: long-

range proton-coupled electron transfer?, Chem Rev 103, 2167-201

Herrick J & Sclavi B (2007) Ribonucleotide reductase and the regulation of DNA

replication: an old story and an ancient heritage. Molecular Microbiology, 63, 22-34.

49.7 Fluoruracil ist ein irreversibler Hemmstoff der Thymidylat-Synthase

el Kouni MH (2003) Potential chemotherapeutic targets in the purine metabolism of

parasites, Pharmacol Ther 99, 283-309

van Kuilenburg AB et al (2004) Pyrimidine degradation defects and severe 5-

fluorouracil toxicity, Nucleosides Nucleotides Nucleic Acids 23, 1371-5

49.8 Harnstoff und Harnsäure sind die Hauptabbauprodukte der Nucleotide

van Gennip AH, van Kuilenburg AB (2000) Defects of pyrimidine degradation: clinical,

molecular and diagnostic aspects, Adv Exp Med Biol 486, 233-41

Beck H, Dobritzsch D, & Piskur J (2008) Saccharomyces kluyveri as a model

organism to study pyrimidine degradation. Fems Yeast Research, 8, 1209-1213.

50 Koordination und Integration des Stoffwechsels

50.1 Die metabolischen Homöostase jeder Einzelzelle wird bedarfsgerecht eingestellt

Lage R, Dieguez C, Vidal-Puig A, & Lopez M (2008) AMPK: a metabolic gauge

regulating whole-body energy homeostasis. Trends in Molecular Medicine, 14, 539-

549.

Wheatcroft SB & Kearney MT (2009) IGF-dependent and IGF-independent actions of

IGF-binding protein-1 and-2: implications for metabolic homeostasis. Trends in

Endocrinology and Metabolism, 20, 153-162.

50.2 Glucose-6-phosphat, Pyruvat und Acetyl-CoA markieren metabolische Knotenpunkte

Cappellini MD & Fiorelli G (2008) Gluclose-6-phosphate dehydrogenase deficiency.

Lancet, 371, 64-74.

Roche TE & Hiromasa Y (2007) Pyruvate dehydrogenase kinase regulatory

mechanisms and inhibition in treating diabetes, heart ischemia, and cancer. Cellular

and Molecular Life Sciences, 64, 830-849.

50.3 Transportvorgänge tragen zur Aufrechterhaltung der metabolischen Homöostase bei

Kellett GL, Brot-Laroche E, Mace OJ, & Leturque A (2008) Sugar absorption in the

intestine: The role of GLUT2. Annual Review of Nutrition, 28, 35-54.

Wu IC, Ohsawa I, Fuku N, & Tanaka M (2010) Metabolic analysis of 13C-labeled

pyruvate for noninvasive assessment of mitochondrial function. Ann N Y Acad Sci,

1201.

121

50.4 Die Koordination des Stoffwechsels beruht auf einer Arbeitsteilung zwischen Organen

Kraemer FB & Shen WJ (2006) Hormone-sensitive lipase knockouts. Nutrition &

Metabolism, 3. (PDF)

Maalouf M, Rho JM, & Mattson MP (2009) The neuroprotective properties of calorie

restriction, the ketogenic diet, and ketone bodies. Brain Research Reviews, 59, 293-

315. (PDF)

50.5 Hormone orchestrieren den Gesamtstoffwechsel eines Organismus

Newsholme EA, Dimitriadis G (2001) Integration of biochemical and physiologic

effects of insulin on glucose metabolism, Exp Clin Endocrinol Diabetes 109 Suppl 2,

122-34

Silva JE (2006) Thermogenic mechanisms and their hormonal regulation.

Physiological Reviews, 86, 435-464. (PDF)

50.6 Glucose ist die wichtigste Regelgröße bei Nahrungsaufnahme und Hunger

Herman MA & Kahn BB (2006) Glucose transport and sensing in the maintenance of

glucose homeostasis and metabolic harmony. Journal of Clinical Investigation, 116,

1767-1775. (PDF)

Airley RE & Mobasheri A (2007) Hypoxic regulation of glucose transport, anaerobic

metabolism and angiogenesis in cancer: Novel pathways and targets for anticancer

therapeutics. Chemotherapy, 53, 233-256.

Bansal P & Wang QH (2008) Insulin as a physiological modulator of glucagon

secretion. American Journal of Physiology-Endocrinology and Metabolism, 295,

E751-E761. (PDF)

50.7 Der Organismus antizipiert Situationen erhöhten Energiebedarfs durch gezielte Stoffwechselanpassungen

Febbraio MA (2001) Alterations in energy metabolism during exercise and heat

stress, Sports Med 31, 47-59

122

123

Seematter G et al (2004) Relationship between stress, inflammation and metabolism,

Curr Opin Clin Nutr Metab Care 7, 169-73

Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, & Mikhailidis DP (2009) The

Pathogenetic Role of Cortisol in the Metabolic Syndrome: A Hypothesis. Journal of

Clinical Endocrinology & Metabolism, 94, 2692-2701. (PDF)

50.8 Langfristige Anpassung des Energiestoffwechsels

Fruhbeck G (2006) Intracellular signalling pathways activated by leptin. Biochemical

Journal, 393, 7-20. (PDF)

Soares JB & Leite-Moreira AF (2008) Ghrelin, des-acyl ghrelin and obestatin: Three

pieces of the same puzzle. Peptides, 29, 1255-1270.

50.9 Störungen des Glucosestoffwechsels führen zu schwerwiegenden Erkrankungen

Khaw KT & Wareham N (2006) Glycated hemoglobin as a marker of cardiovascular

risk. Current Opinion in Lipidology, 17, 637-643.

Hipolito L, Sanchez MJ, Polache A, & Granero L (2007) Brain metabolism of ethanol

and alcoholism: An update. Current Drug Metabolism, 8, 716-727.

Barsotti A, Giannoni A, Di Napoli P, & Emdin M (2009) Energy Metabolism in the

Normal and in the Diabetic Heart. Current Pharmaceutical Design, 15, 836-840.