1 Metabolism of protein & amino acids 2 A. The physiological & nutritious function of...

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Metabolism of protein &

amino acids

2

A. The physiological &

nutritious function of

proteins

3

B. nitrogen balance &

protein requirement

4

1. nitrogen balance

a. concept

b. experiment

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c. 3 conditions

nitrogen equilibrium

negative nitrogen balance

positive nitrogen balance

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2. minimal requirements of

protein

3.essential amino acids and

their biological value

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an indicator to valuate the

nutritional value of the proteins

biological value

100 的吸收量的保留值

蛋白质的生理价值＝N

N

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4. Complementary function

of proteins

B. Digestion ,absorption,&

putrefaction of proteins

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diet protein amino acids digestion

Proteolytic

enzyme

a. digestion

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b. absorption

site

mechanism

characteristics

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c. putrefaction

concept

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未被消化的蛋白质 , 未被吸收的氨基酸，肽

large intestine

bacterias

Decarboxylation

deamination

有毒； amine ,H2S indole

hydroxybenzene 、 ammonia （ NH3) 、

other ：CO2,CH4

Nutriment

Fatty acid 、 vit

Absorption in intestine excrete

blood

liver

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• decarboxylation

• reductive & deamination

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18

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• the sources of ammonia in the

intestine

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blood infiltrate intestine

kidney

excrete （ 20g ）

NH2-CO-NH2

liver

NH3

(25%)7g

NH2-CO-

NH2

urease (bacterias)

2NH3+CO2 （ 4g

）

importance sources of blood ammonia-----

- absorpted from intestine

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C. general metabolism

of amino acids

1. Sketch plan

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Dietary protein

Tissue protein

amination of α—keto acids

degradation

Synthesis

85%

Non essential A.A

Digest,absorption

deamination

amines

NH3 α—keto acids

oxidation Glucose, fats

N.EAA

decarboxylation

Amino acid

metabolic

pool

urea

other substances

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2. deamination of amino acids

a.oxidative deamination

1) reaction

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2 ) enzymes

• L-amino acid oxidase

• D-amino acid oxidase

• L-glutamate dehydrogenase

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• characteristics

b . transamination

1) reaction

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2) important transamination

system.

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glutamic pyruvic transamination system （ glutamic pyruvic transaminase,GPT ）（ alanine transaminase,ALT ）

glutamic oxaloacetic transamination systen: （ glutamic oxaloacetic transaminase, ,GOT ）（ aspartate transaminase,AST)

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NH2 O O NH2

Glu 丙酮酸 α— 酮戊二酸 Ala

NH2 CO-COOH O CH-COOH

NH2

Glu 草酰乙酸 α— 酮戊二酸 ASP

COOH-(CH2)2-CH-COOH + CH3-C-COOH COOH-(CH2)2-C-COOH+CH3-CH-COOH

COOH-(CH2)2-CH-COOH + CH2COOH COOH-(CH2)2-C-COOH+CH2-COOH

ALT

AST

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2) enzyme & coenzyme

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3) biological significance &

characteristics

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c. combined deamination

1) reaction

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40

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2) biological significance &

characteristics

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d. purine nucleotide cycle

1) site

2) reaction

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3) characteristics

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d. nonoxidative deamination

• dehydrate deamination

• direct deamination

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3. Metabolism of ammonia

a. the sources of ammonia

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the detail about the sources

of ammonia

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protein

putrefaction

Urea cycle in liver&intestine

Absorption in intestine

（ oxidation of amine )

　 deamination

Blood ammonia

Ala

(liver)

Gln

  sources of blood ammonia

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* protein putrefaction

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blood infiltrate intestine

kidney

excrete （ 20g ）

NH2-CO-NH2

liver

NH3

(25%)7g

NH2-CO-

NH2

urease

2NH3+CO2 （ 4g

）

importance sources of blood ammonia-----

- absorpted from intestine

NH4 excrete from feces

*Urea cycle in liver & intestine

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According to the pH in intestine

pH NH3 + H+ NH 4+ excrete

  pH absorpted to venous blood

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protein

putrefaction

Urea cycle in liver&intestine

Absorption in intestine

（ oxidation of amine )

　 deamination

Blood ammonia

Ala

(liver)

Gln

  sources of blood ammonia

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* hydrolysis of Gln

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• the fates of ammonia

produced in renal cell

excrete to the kidney

reabsorption to vein blood

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According to renal tube pH

pH NH3 + H+ NH4+ excrete

 pH absorpted to venous blood

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Putrefaction in

small intestine

Intestine-liver

cycle of urea

Absorption

In small intestine

（ oxidation of amines ）

deamination of A.A

Ammonia

in blood

Ala in liver

GLn

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*Ala

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b. The transportation of

ammonia

• synthesis & utilize of Gln

materials : Glu , NH3

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energy: ATP

enzyme: Gln synthetase

reaction:

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product: Gln

Biological significances

,

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• glucose-alanine cycle

process

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65

biological significance

66

Putrefaction in

small intestine

Intestine-liver

cycle of urea

Absorption

In small intestine

（ oxidation of amines ）

deamination of A.A

Ammonia

in blood

Ala in liver

GLn

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c. the fates of ammonia

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Synthesis of non essential A.A or other nitrogen compounds

muscle or other tissues

Gln

muscle

ureaNH3

Ala

liver

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1) synthesis of urea---main

outlet of ammonia

a. site

b. process (ornithine cycle )

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* 肝脏是合成尿素最主要的器官

血 尿

切肝犬 尿素 氨 尿素

用氨基酸饲养切肝犬 尿素 氨基酸

尿素 切肾犬

急性黄色肝委缩

氨基酸

尿素 （ - ） 氨 尿素 （ - ）

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This cycle included:

1 overall reaction

2 materials

3 stages

4 steps

5 enzymes

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a. materials

15NH4Cl

NaH14CO3

Feed

dogs

14C=O

15NH2

15NH2

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b. 3 stages

ornithine+ NH3+ CO2 citrulline+H20

citrulline+ NH3 arginine+ H20

arginine+ H20 urea+ ornithine

2ATP

1ATP

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NH2 NH2

(CH2)3 C=O

+ NH3+ CO2 NH + H2O

CH NH2

(CH2)3

CH NH2 ornithine

citrulline

COOH

COOH

2ATP

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NH2 NH2

C=O

NH + NH3 NH + H2O

(CH2)3

CH-NH2

COOH Citrullinc Arginine

C=NH

(CH2)3

CH-NH2

COOH

1ATP

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NH2

C=NH

NH +H2O

(CH2)3

CH-NH2

COOH

Arginine

NH2 + (CH2)3

C=O CH-NH2

Orrnithine

COOH

NH2

NH2

urea

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NH3 （ 2 molecules ）

CO2 （ 1 molecules ） materials

urea

H2O

products

Ornithine

Citrulline

arginine

intermediates

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c. Intermediate process

( 4 steps, 5 enzymes )

1) synthesis of carbomoyl

phosphate (mitochondria)

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NH3+CO2+H2O+2ATP

NH2-CO-O~PO32-+Pi

carbomoyl phosphate synthetase 1

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• enzyme

carbamoyl phosphate synthetase 1 carbamoyl phosphate synthetase II

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carbomoyl phosphate carbomoyl phosphate

synthetase 1 synthetase II

Site mitochondria cytosol

source of NH3 Gln

nitrogenActivator AGA -

(N-Acetylglutamic acid )FinalProduct urea pyrimidine

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2) synthesis of citrulline

(mitochondria)

• enzyme

ornithine transcarbomoylase

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3) synthesis of arginine

(cytosol)

• enzyme

Argininosuccinate synthetase,ASAS Argininosuccinate lyase ASAL

ASAS------ Key enzyme

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4) cleavage of arginine

(cytosol)

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d. Overall reaction

3ATP+CO2+2NH3 +H2O NH2-CO-NH2

f. summarize

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c. Regulation of urea synthesis

food

enzymes (AGA)

intermediates

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d. biological significant of

urea synthesis

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Synthesis of non essential A.A or other nitrogen compounds

muscle or other tissues

Gln

muscle

ureaNH3

Ala

liver

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4. Metabolism of -keto acids

Amino

acid

NH3

Ala

Gln

ureaAmination of a-keto acids

Amination or transamination

To form non E.A.A.

Conversion of fat,glucose

Via TCA cycle oxidized to CO2 & H2O

-keto acids

100

1) Amination or transamination

To form non E.A.A.

α- ketoglutarate Glu

Pyruvate Ala oxaloacetate Asp

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Glu

α- ketoglutarate

oxaloacetate

Asp

TCA cycle

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2) Conversion to lipids or

carbohydrates

glycogenic amino acid, such as : Ala 、 Arg 、 Asp etc （ 13 ）ketogenic amino acid such as:

leu lys (2)

glycogenic & ketogenic amino

acids such as : Ilu,Phe,Trp,Tye

103

TCA cycle is the hinge

of metabolism of lipids ,

carbohydrates, proteins

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*

*

*

*

*

*

*

*

105

3) oxidation & provide energy

3. decarboxylation

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Amino acids - CO

2

α-keto acids

amines

Non E.A.A

Conversion to lipids, carbohydrates

TCA cycle- NH 3

107

Enzymes & coenzyme

some important amines

108

a.γ-amino butyric acid

(GABA ）

formation

109

enzyme

function

metabolic fate

110

b. 5-hydroxy tryptamine or

( serotonin ）formation

111

function

c. taurine

formation

112

function

d. histamine

formation

113

e. polyamines

formation

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D. metabolism of individual

amino acids

1. one carbon units

116

Concept

kinds

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118

the carrier of one carbon unites

--------------THF

120

the sources & conversion

NH2-CH——COOH +FH4 NH2-CH— （ CH2 ） 2+N5-CH3-FH4 转甲基酶

（ CH2 ）

2

S

CH3

SH COOH

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122

123

function

one carbon units &

medicine

124

2. metabolism of sulfur-

containing amono acids

types

125

Met

cysteine,Cys cystine

126

a.Met and Transfer of

methyl group

S-adenosylmethionine

(SAM)

127

Structure of SAM

128

Function of SAM

methionine cycle

B12 & methionine

cycle

129

B12

130

3. metabolism of cystein &

cystine

structure & characteristics

131

Formation of GSH

132

Catabolism of Cys

Cys

-NH2

pyruvate NH3 H2S

H2S SO42- 2ATP

Excrete in uria PAPS （ active sulfate ）

133

The structure & function

of PAPS

( 3’-phosphoadenosine-

5’phosphosulfate

134

135

4. metabolism of side

chain amino acids

Type: Val,Ile,Leu

Catabolic process

(extrahepatic tissue )

136

Val 、 Ile 、 Leu

α-ketoacids

α-ketoglutarate Glu NH3

Gln

Ala pyruvate

liver

urea glyconeogenesis

Blood

137

5. metabolism of

aromatic amino acids

Type: Phe,Tyr,Trp

Catabolic process

(hepatic tissue)

138

Catabolic process of Phe

139

140

Albinism,

Phenylketonuria, (PKU)

Alkaptonuria

BCAA/AAA 3:1