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