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

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Presentation on theme: "蛋白质的分解代谢 Protein Degradation and Amino Acids Metablism."— Presentation transcript:

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 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 Classification of amino acids

7 Nonessential Essential AlanineArginine* Asparagine Histidine * Aspartate Valine CysteineLysine Glutamate Isoleucine Glutamine Leucine Glycine Phenylalanine ProlineMethionine SerineThreonine TyrosineTyrptophan *The amino acids Arg, His are 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 1.Degraded by ubiquitin( 泛素 ) label 2. Degraded by the protease and the peptidase in the Lysosome( 溶酶体) Degradation of proteins

10  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 1. Degraded by ubiquitin( 泛素 ) label

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 The ubiquitin degradation pathway E1-S- E1-SH E2-S- E1-SH E2-SH ATP AMP+PPiE3 ubiquitinational protein ATP 26S Proteasome 20S Proteasome ATP 19S regulate substrate E1 : activiting enzyme E2 : carrier protein E3 : ligase ( ubiquitin )

13 II. Amino acids Degradation

14 The catabolism of amino acids

15 A. Transamination B. Oxidative deamination C. Combined Deamination I. 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 AA  -Keto glutarate  -Keto acid Asp Oxaloacetate malate fumarate IMP AMP H2OH2O NH 3 2. Transamination + purine nucleotide cycle aminotransferases AST

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

22 L-Glu decarboxylase – CO 2 GABA L-Glu  -aminobutyric acid (GABA) Glutamine can be decarboxylated in a similar PLP-dependent fashion, outputting  -aminobutyric acid (neurotransmitter, GABA)

23 – CO 2 Histidine decarboxylase Histamine L-Histidine 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%) ( CO 2 +H 2 O )  Glucogenesis and ketogenesis

25 Fate of the C-Skeleton of Amino Acids

26  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 Ⅳ. ammonia metabolism

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 (Mitochondria and cytosol)  Excretion via kidney  To convert ammonia to urea for final excretion

31 2ADP+Pi CO 2 + NH 3 + H 2 O 氨基甲酰磷酸 2ATP N- 乙酰谷氨酸 Pi 鸟氨酸 瓜氨酸 精氨酸 延胡索酸 氨基酸 草酰乙酸 苹果酸 α- 酮戊 二酸 谷氨酸 α- 酮酸 精氨酸代 琥珀酸 瓜氨酸 天冬氨酸 ATP AMP + PPi 鸟氨酸 尿素 线粒体 胞 液胞 液 The urea cycle :

32 UREA CYCLE (liver) 1. Overall Reaction: NH 3 + HCO 3 – + aspartate + 3 ATP + H 2 O  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 NH 4 +

35 III. Biosynthesis of Amino acids

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

37 Biosynthesis of Amino Acids

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