Lect18 - Lecture 18 Protein Degradation 1 Important...

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1 Lecture 18 Protein Degradation
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2 Important concepts 1. Understand protein degradation Understand the ubiquitin-proteasome system Describe the degradation steps 2. Understand degradation of amino acids Understand transamination to deaminate Understand the mechanism and the role of PLP
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3 Must obtain from diet
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4 Digestion of dietary proteins Pepsin, prefer acidic environment in stomach
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5 Regulated Degradation: Ubiquitin-Proteasome System Aaron Ciechanover Avram Hershko Irwin Rose Nobel Prize in Chemistry, 2004 Alex Varshavsky Only 3 people can win the Nobel Prize …
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6 Poly-ubiquitin (Usually Lys-48 one ubiquitin to C-terminus of another) •76 residues, highly conserved •C terminus attached to Lys in the protein to be degraded Ubiquitin
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7
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8 Regulated Degradation: Ubiquitin-Proteasome System Sulfhydryl group of a Cys in E1 ATP driven E1 — Ubiquitin Activating Enzyme E2 — Ubiquitin Conjugating Enzyme E3 — Ubiquitin Protein Ligase
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9 Comparison: Activating Fatty Acid Activation with ATP : Acyl-CoA synthetases (fatty acid thiokinases) Conserve energy in high-energy thioester Occurs in outer mitochondrial membrane
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10 Comparison: UDP-glucose Pyrophosphorylase: Activating glucose-1-phosphate through a coupled reaction From phosphoglucomutase Coupled Reactions
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Which proteins are degraded?
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Lect18 - Lecture 18 Protein Degradation 1 Important...

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