蛋白质的分解代谢
Protein Degradation and AmProtein Degradation and Amino Acids Metablismino 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 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. )
• 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
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
Degradation oDegradation of dietary protef dietary proteinsins
1. Degraded by ubiquitin( 泛素 ) label
2. Degraded by the protease and the peptidase in the Lysosome( 溶酶体)
Degradation of proteins
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
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
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 )
II. Amino acids Degradation
The catabolism of amino acids
A. Transamination
B. Oxidative deamination
C. Combined Deamination
I. 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
AA
-Keto glutarate
-Keto acid
Asp
Oxaloacetatemalate fumarate
IMP
AMP
H2O
NH3
2. Transamination + purine nucleotide cycle
aminotransferases AST
II. Decarboxylation
The decarboxylation of AAs produce some neurotransmitters’ precursors – bioactive amines
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)
– 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。
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
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
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.
Gln regeneration
Urea synthesis
Synthesis in liver (Mitochondria and cytosol)
Excretion via kidney
To convert ammonia to urea for final excretion
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 :
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
Major Ammonium ion carrier
Ammonium Ion Is Assimilated into Amino Acids Through Glutamate and Glutamine
Biosynthesis of Amino Acids
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