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蛋白质的分解代谢 PowerPoint Presentation
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蛋白质的分解代谢

蛋白质的分解代谢

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蛋白质的分解代谢

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  1. 蛋白质的分解代谢 Protein Degradation and Amino Acids Metablism

  2. Contents • Protein degradation • Amino Acid Degradation • Biosynthesis of amino acids

  3. I. Protein Degradation

  4. Biological Functions of Proteins • Enzymes • Transport proteins • Nutrient and storage proteins • Contractile or motile proteins • Structural proteins • Defense proteins • Regulatory proteins • Other proteins

  5. Nitrogen balance • Zero or total nitrogen balance: • the intake = the excretion • (adult) • Positive nitrogen balance: • the intake > the excretion • (during pregnancy, infancy, childhood and recovery from severe illness or surgery ) • Negative nitrogen balance: • the intake < the excretion • (following severe trauma, surgery or infections. Prolonged periods of negative balance are dangerous and fatal. )

  6. Classification of amino acids • non-essential amino acids • - can be synthesized by an organism • - usually are prepared from precursors in 1-2 steps • Essential amino acids *** • - can not be made endogenously • - must be supplied in diet

  7. *The amino acidsArg, Hisare considered “conditionally essential” for reasons not directly related to lack of synthesis and  they are essential  for growth only

  8. Degradation of dietary proteins

  9. Degradation of proteins • Degraded by ubiquitin(泛素) label 2. Degraded by the protease and the peptidase in the Lysosome(溶酶体)

  10. 1. Degraded by ubiquitin(泛素) label • Ubiquitin, a extremely well conserved 76-residue protein, Ubiquitin binds lysine side chain • Degrade abnormal protein of her own • Targets for hydrolysis by proteosomes in cytosol and nucleus • ATP required

  11. 2. Degraded by the protease and the peptidase in the Lysosome(溶酶体) • non- ATP required • the hydrolysis-selective are bad • Degrade adventive protein

  12. E2-S- E1-S- The ubiquitin degradation pathway ATP AMP+PPi E3 E2-SH (ubiquitin) E1-SH E2-SH E1-SH E1:activiting enzyme E2:carrier protein E3:ligase ubiquitinational protein ATP 19S regulate substrate ATP 20S Proteasome 26S Proteasome

  13. II. Amino acids Degradation

  14. The catabolism of amino acids

  15. I. Deamination A. Transamination B. Oxidative deamination C. Combined Deamination

  16. A. Transamination • Transamination by Aminotransferase (transaminase) • always involve PLP coenzyme (pyridoxal phosphate) • reaction goes via a Schiff’s base intermediate • all transaminase reactions are reversible

  17. Transamination aminotransferases

  18. B. Oxidative Deamination • L-glutamate dehydrogenase (in mitochondria)

  19. C. Combined Deamination 1. Transamination + Oxidative Deamination ?

  20. NH3 AA Asp IMP -Keto glutarate H2O aminotransferases AST 2. Transamination +purine nucleotide cycle AMP -Keto acid Oxaloacetate fumarate malate

  21. II. Decarboxylation The decarboxylation of AAs produce some neurotransmitters’ precursors – bioactive amines

  22. L-Glu decarboxylase – CO2 GABA L-Glu -aminobutyric acid (GABA) Glutamine can be decarboxylated in a similar PLP-dependent fashion, outputting -aminobutyric acid (neurotransmitter, GABA)

  23. Histidine decarboxylase – CO2 L-Histidine Histamine Histamine 强烈的血管舒张剂。增加血管的通透性,降低血压,甚至死亡。

  24. III. The metabolism of α-ketoacid • Biosynthesis of nonessential amino acids • TCA cycle member + amino acid α-keto acid + nonessential amino acid • A source of energy (10%) ( CO2+H2O ) • Glucogenesis and ketogenesis

  25. Fate of the C-Skeleton of Amino Acids

  26. Ⅳ . ammonia metabolism • Fix ammonia onto glutamate to form glutamine and use as a transport mechanism • Transport ammonia by alanine-glucose cycle and Gln regeneration • Excrete nitrogenous waste through urea cycle

  27. Transportation of ammonia • alaninie - glucose cycle * • regenerate Gln

  28. Alanine-Glucose cycle • In the liver alanine transaminase tranfers the ammonia to α-KG and regenerates pyruvate. The pyruvate can then be diverted into gluconeogenesis. This process is refered to as the glucose-alanine cycle.

  29. Gln regeneration

  30. Urea synthesis • Synthesis in liver (Mitochondriaandcytosol) • Excretion via kidney • To convert ammonia to urea for final excretion

  31. CO2 + NH3+ H2O 2ATP N-乙酰谷氨酸 2ADP+Pi 氨基甲酰磷酸 Pi 瓜氨酸 鸟氨酸 瓜氨酸 氨基酸 ATP α-酮戊 二酸 鸟氨酸 AMP + PPi 天冬氨酸 精氨酸代 琥珀酸 谷氨酸 草酰乙酸 尿素 α-酮酸 精氨酸 延胡索酸 苹果酸 The urea cycle: 线粒体 胞 液

  32. UREA CYCLE (liver) 1. Overall Reaction: NH3 + HCO3– + aspartate + 3 ATP + H2O  urea + fumarate + 2 ADP + 2 Pi + AMP + ppi 2. Requires 5 enzymes: 2 from mitochondria and 3 from cytosol

  33. Regulation of urea cycle • The intake of the protein in food:the intake↑↑urea synthesis • AGA:CPS I is an allosteric enzyme sensitive to activation by N-acetylglutamate(AGA)which is derived from glutamate and acetyl-CoA. • All intermediate products accelerate the reaction • Rate-limiting enzyme of urea cycle is argininosuccinate synthetase(精氨酸代琥珀酸合成酶)

  34. The Urea Cycle is Linked to the Citric Acid Cycle NH4+

  35. III. Biosynthesis of Amino acids

  36. Ammonium Ion Is Assimilated into Amino Acids Through Glutamate and Glutamine Major Ammonium ion carrier

  37. Biosynthesis of Amino Acids