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1、杨荣武杨荣武 生物化生物化 学原理学原理 第二版第二版 Chapter31 AA Metabolism Outline Hydrolysis of Protein Breakdown of amino acids Synthesis of amino acids and their derivatives Protein degradation Extracellular degradation Intracellular degradation ATP-independent occurs in lysosomes ATP-dependent i) N-end rule and sequen

2、ce ii) The role of Ubiquitin iii) Proteasome 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

3、lives of 3 min or less PEST proteins N 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 $Protein

4、s 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 inhibited by glutamine Tyr397 inactivated Regulation of the activity of E.

5、coli glutamine synthetase Nitrogen excretion NH4+ Uric acid Urea + uric acid How are ammonia fed into the urea cycle? The urea cycle The urea cycle Regulation of the urea cycle carbamoyl phosphate synthetase 1, is allosterically activated by N-acetylglutamate N-acetylglutamate is synthesized from gl

6、utamate and acetyl-CoA the remaining enzymes regulated by substrate levels substrate level buildup stimulates urea cycle enzymes product buildup inhibits urea cycle enzymes Amino Acid Biosynthesis $Plants and microorganisms can make all 20 amino acids and all other organisms need N metabolites $In these organisms, glutamate is the source of N, via transamination (aminotransferase) reactions $Mammals can make only 10 of the 20 amino acids $The others are classed as essential amino acids and must be obtained in the diet $All amino acids a

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