蛋白质的分解代谢 Protein Degradation and Amino Acids Metablism.
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Transcript of 蛋白质的分解代谢 Protein Degradation and Amino Acids Metablism.
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蛋白质的分解代谢
Protein Degradation and AmProtein Degradation and Amino Acids Metablismino Acids Metablism
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Contents
Protein degradation Amino Acid Degradation Biosynthesis of amino acids
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I. Protein Degradation
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Biological Functions of Proteins
Enzymes Transport proteins Nutrient and storage proteins Contractile or motile proteins Structural proteins Defense proteins Regulatory proteins Other proteins
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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. )
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• 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
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Nonessential Essential
Alanine Arginine*
Asparagine Histidine *
Aspartate Valine
Cysteine Lysine
Glutamate Isoleucine
Glutamine Leucine
Glycine Phenylalanine
Proline Methionine
Serine Threonine
Tyrosine Tyrptophan *The amino acids Arg, His are considered “conditionally essential” for reas
ons not directly related to lack of synthesis and they are essential for growth
only
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Degradation oDegradation of dietary protef dietary proteinsins
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1. Degraded by ubiquitin( 泛素 ) label
2. Degraded by the protease and the peptidase in the Lysosome( 溶酶体)
Degradation of proteins
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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 cyto
sol and nucleus ATP required
1. Degraded by ubiquitin( 泛素 ) label
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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
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The ubiquitin degradation pathway
E1-S-
E1-SH
E2-S-
E1-SH
E2-SH
E2-SH
ATP AMP+PPi E3
ubiquitinational protein
ATP
26S Proteasome
20S Proteasome
ATP
19S regulate substrate
E1 : activiting enzyme
E2 : carrier protein E3 : ligase
( ubiquitin )
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II. Amino acids Degradation
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The catabolism of amino acids
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A. Transamination
B. Oxidative deamination
C. Combined Deamination
I. Deamination
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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
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Transamination
aminotransferases
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B. Oxidative Deamination
• L-glutamate dehydrogenase (in mitochondria)
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C. Combined Deamination
?
1. Transamination + Oxidative Deamination
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AA
-Keto glutarate
-Keto acid
Asp
Oxaloacetatemalate fumarate
IMP
AMP
H2O
NH3
2. Transamination + purine nucleotide cycle
aminotransferases AST
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II. Decarboxylation
The decarboxylation of AAs produce some neurotransmitters’ precursors – bioactive amines
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L-Glu decarboxylase
– CO2
GABA
(CH2)2
COOH
CH2NH2
L-Glu
(CH2)2
COOH
CHNH2
COOH
-aminobutyric acid (GABA)
Glutamine can be decarboxylated in a similar PLP-dependent fashion, outputting
-aminobutyric acid (neurotransmitter, GABA)
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– CO2
Histidine decarbo
xylase
Histamine
CH2CH2NH2
NHN
L-Histidine
COOHCCH2
NH2NHN
H
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。
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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
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Fate of the C-Skeleton of Amino Acids
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Fix ammonia onto glutamate to form glutamine a
nd use as a transport mechanism
Transport ammonia by alanine-glucose cycle and
Gln regeneration
Excrete nitrogenous waste through urea cycle
Ⅳ . ammonia metabolism
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Transportation of ammonia
• alaninie - glucose cycle *
• regenerate Gln
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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.
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Gln regeneration
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Urea synthesis
Synthesis in liver (Mitochondria and cytosol)
Excretion via kidney
To convert ammonia to urea for final excretion
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2ADP+Pi
CO2 + NH3 + H2O
氨基甲酰磷酸
2ATPN- 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
The urea cycle :
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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
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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 )
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The Urea Cycle is Linked to the Citric Acid Cycle
NH4+
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III. Biosynthesis of Amino acids
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Major Ammonium ion carrier
Ammonium Ion Is Assimilated into Amino Acids Through Glutamate and Glutamine
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Biosynthesis of Amino Acids