第二十章氨基酸代谢.pptVIP

Protein Degradation AA Metabolism Protein degradation Extracellular degradation Intracellular degradation ATP-independent occurs in lysosomes ATP-dependent i) N-end rule and “PEST” sequence ii) The role of Ubiquitin(泛素） iii) Proteasome（蛋白酶体） iiii) Highly regulated N-end rule A proteins half-life correlates with its N-terminal residue. Proteins with N-terminal Met, Ser, Ala, Thr, Val, or Gly have half lives greater than 20 hours. Proteins with N-terminal Phe, Leu, Asp, Lys, or Arg have half lives of 3 min or less PEST proteins It has also been found that proteins rich in Pro (P), Glu (E), Ser (S) and Thr (T), called PEST proteins, are more rapidly degraded than other proteins. Ubiquitin Ubiquitin is a highly-conserved, 76 residue (8.5 kDa) protein found widely in eukaryotes Proteins are tagged for selective destruction by ubiquitin An isopeptide bond links the terminal carboxyl of ubiquitin to the e-amino group of a lysine residue of a condemned protein. Three enzymes are involved, designated E1, E2 E3. Proteasome 20S Large multifunctional protease complex in the cytosol that degrades intracellular ubiquitin-tagged proteins. (Just like a barrel) 19S regulatory subunit (like a cap) This regulatory cap complex recognizes multi-ubiquitinated proteins, unfolds them, removes ubiquitin chains, and provides a passageway for threading unfolded proteins into the core complex. AA Metabolism Amino Acid Degradation 1) Removal of the -amino group Deamination i) L-Amino Acid Oxidase ii) D-Amino Acid Oxidase iii) Glutamate Dehydrogenase Transamination Combined Deamination 2) Fates of C skeleton ketogenic aa glycogenic aa 3) Detoxification and Excretion of Ammonia Amino Acid Synthesis L-Amino Acid Oxidase L-amino acid oxidase is an enzyme involved in amino acid catabolism. It is a flavoprotein-containing enzyme that catalyzes the reaction below, yielding a hydrogen peroxid