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蛋白质的分解代谢. Protein Degradation and Amino Acids Metablism. Contents Protein degradation Amino Acid Degradation Biosynthesis of amino acids. I. Protein Degradation. Biological Functions of Proteins. Enzymes Transport proteins Nutrient and storage proteins
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蛋白质的分解代谢 Protein Degradation and Amino Acids Metablism
Contents • Protein degradation • Amino Acid Degradation • Biosynthesis of amino acids
Biological Functions of Proteins • Enzymes • Transport proteins • Nutrient and storage proteins • Contractile or motile proteins • Structural proteins • Defense proteins • Regulatory proteins • Other proteins
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. )
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
*The amino acidsArg, Hisare considered “conditionally essential” for reasons not directly related to lack of synthesis and they are essential for growth only
Degradation of proteins • Degraded by ubiquitin(泛素) label 2. Degraded by the protease and the peptidase in the Lysosome(溶酶体)
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
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
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
I. Deamination A. Transamination B. Oxidative deamination C. Combined Deamination
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
Transamination aminotransferases
B. Oxidative Deamination • L-glutamate dehydrogenase (in mitochondria)
C. Combined Deamination 1. Transamination + Oxidative Deamination ?
NH3 AA Asp IMP -Keto glutarate H2O aminotransferases AST 2. Transamination +purine nucleotide cycle AMP -Keto acid Oxaloacetate fumarate malate
II. Decarboxylation The decarboxylation of AAs produce some neurotransmitters’ precursors – bioactive amines
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)
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。
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
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
Transportation of ammonia • alaninie - glucose cycle * • regenerate Gln
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.
Urea synthesis • Synthesis in liver (Mitochondriaandcytosol) • Excretion via kidney • To convert ammonia to urea for final excretion
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
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
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)
Ammonium Ion Is Assimilated into Amino Acids Through Glutamate and Glutamine Major Ammonium ion carrier