Download Essential amino acids

蛋白质的分解代谢
Protein Degradation and
Amino Acids Metablism
Contents
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Protein degradation
Amino Acid Degradation
Biosynthesis of amino acids
I.
Protein Degradation
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
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
reasons not directly related to lack of synthesis and they are essential for
growth only
Degradation
of dietary
proteins
Degradation of proteins
1. 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 76residue 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
The ubiquitin degradation pathway
ATP AMP+PPi
E1-S（ubiquitin）
E3
E2-SH
E2-SE1-SH
E1-SH
E2-SH
E1：activiting enzyme
E2：carrier protein E3：ligase
ubiquitinational protein
19S regulate
substrate
ATP
ATP
20S
Proteasome
26S
Proteasome
II. Amino acids Degradation
The catabolism of amino acids
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
aminotransferasesAST
-Keto
acid
2. Transamination + purine
nucleotide cycle
Oxaloacetate
malate
fumarate
AMP
II. Decarboxylation
The decarboxylation of AAs produce some neurotransmitters’
precursors – bioactive amines
-aminobutyric acid (GABA)
Glutamine can be decarboxylated in a similar PLP-dependent fashion, outputting
-aminobutyric acid (neurotransmitter, GABA)
COOH
COOH
(CH 2)2
CHNH 2
COOH
L-Glu
L-Glu decarboxylase
– CO2
(CH 2)2
CH 2NH 2
GABA
H
N
CH2 C COOH
NH
NH2
L-Histidine
Histamine
强烈的血管舒张剂。增加
CH2CH2NH 2
血管的通透性，降低血压，
甚至死亡。
N
NH
Histamine
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
Fate of the C-Skeleton of Amino Acids
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 glucosealanine cycle.
Gln regeneration
Urea synthesis
 Synthesis in liver (Mitochondria and cytosol)
 Excretion via kidney
 To convert ammonia to urea for final excretion
The urea cycle：
CO2 + NH3 + H2O
2ATP
N-乙酰谷氨酸
线粒体
2ADP+Pi
氨基甲酰磷酸
Pi
瓜氨酸
鸟氨酸
瓜氨酸
ATP
AMP + PPi
天冬氨酸
鸟氨酸
尿素
胞液
精氨酸代
琥珀酸
草酰乙酸
精氨酸
延胡索酸
苹果酸
α-酮戊
二酸
谷氨酸
氨基酸
α-酮酸
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)
The Urea Cycle is Linked to the Citric Acid Cycle
NH4+
III. Biosynthesis of
Amino acids
Ammonium Ion Is Assimilated into Amino Acids
Through Glutamate and Glutamine
Major Ammonium ion carrier
Biosynthesis of Amino Acids