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Metabolism of

protein

&

amino acids

A. The physiological & nutritious function of proteins


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B. nitrogen balance & protein requirement

1. nitrogen balance a. concept

b. experiment

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
N 100 N

4. Complementary function

of proteins
B. Digestion ,absorption,&

putrefaction of proteins
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a. digestion

digestion diet protein amino acids

Proteolytic
enzyme
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b. absorption site mechanism characteristics


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c. putrefaction

concept

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,
large intestine

bacterias Decarboxylation deamination

amine ,H2S indole

other CO2,CH4

Nutriment

hydroxybenzene ammoniaNH3) Absorption in intestine


blood

Fatty acidvit

excrete

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liver

decarboxylation reductive & deamination

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the sources of ammonia in the intestine

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blood

infiltrate

intestine

kidney

NH2-CO-NH2
(25%)7g liver

NH2-CONH2
urease (bacterias) 2NH3+CO24g

excrete20g NH3

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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decarboxylation
Dietary protein Amino acid degradation Tissue protein Synthesis 85% deamination metabolic pool

amines

amination of keto acids

Non essential A.A urea


other substances

NH3

keto acids
Glucose, fats N.EAA
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oxidation

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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ALT
COOH-(CH2)2-CH-COOH + CH3-C-COOH NH2 Glu O

COOH-(CH2)2-C-COOH+CH3-CH-COOH O Ala NH2

AST
COOH-(CH2)2-CH-COOH + CH2COOH
NH2 CO-COOH COOH-(CH2)2-C-COOH+CH2-COOH O CH-COOH NH2 Glu ASP

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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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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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sources of blood ammonia


oxidation of amine ) protein putrefaction Absorption in intestine Blood ammonia Gln

deamination

Urea cycle in liver&intestine

Ala (liver)
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* protein putrefaction

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*Urea cycle in liver & intestine

blood

infiltrate

intestine

kidney

NH2-CO-NH2
(25%)7g liver

NH2-CONH2
urease 2NH3+CO24g

excrete20g NH3

excrete from feces importance sources of blood ammonia----NH4

- absorpted from 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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sources of blood ammonia


oxidation of amine ) protein putrefaction Absorption in intestine Blood ammonia Gln

deamination

Urea cycle in liver&intestine

Ala (liver)
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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


pH

NH3 + H+

NH4+ excrete

absorpted to venous blood

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oxidation of amines
Putrefaction in small intestine Absorption In small intestine Intestine-liver cycle of urea Ala in liver deamination of A.A

Ammonia
in blood 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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biological significance

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oxidation of amines
Putrefaction in small intestine Absorption In small intestine Intestine-liver cycle of urea Ala in liver deamination of A.A

Ammonia
in blood GLn

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c. the fates of ammonia

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urea

Synthesis of non essential A.A or other nitrogen compounds muscle or other tissues NH3 Gln

liver

muscle Ala
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1) synthesis of urea---main outlet of ammonia

a. site b. process (ornithine cycle )


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*
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This cycle included: 1 overall reaction 2 materials

3 stages 4 steps
5 enzymes
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a.

materials

15NH

4Cl

15NH

Feed
dogs
NaH14CO3

14C=O
15NH 2

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b. 3 stages
2ATP

ornithine+ NH3+ CO2


1ATP

citrulline+H20
arginine+ H20 urea+ ornithine

citrulline+ NH3 arginine+ H20

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NH2
(CH2)3

NH2 C=O

2ATP
NH + H2O (CH2)3 NH2

+ NH3+ CO2 CH

COOH CH ornithine COOH citrulline


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NH2

NH2 C=O 1ATP NH + NH3

NH2

C=NH
NH + H 2O

(CH2)3

(CH2)3

CH-NH2
COOH Citrullinc

CH-NH2
COOH Arginine

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NH2
C=NH NH +H2O NH2 + NH2 (CH2)3

(CH2)3
CH-NH2 COOH Arginine

C=O
NH2

CH-NH2
COOH

urea

Orrnithine 79

materials

NH3 2 molecules
CO2 1 molecules urea

products H2O Ornithine intermediates Citrulline arginine


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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
carbomoyl phosphate synthetase 1

NH2-CO-O~PO32-+Pi

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enzyme

carbamoyl phosphate synthetase 1 carbamoyl phosphate synthetase II

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carbomoyl phosphate synthetase

carbomoyl phosphate synthetase II cytosol Gln -

Site mitochondria source of NH3 nitrogen Activator AGA (N-Acetylglutamic acid )

Final Product

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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urea

Synthesis of non essential A.A or other nitrogen compounds muscle or other tissues NH3 Gln

liver

muscle Ala
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4. Metabolism of -keto acids


Ala Gln NH3 Amino acid -keto acids Conversion of fat,glucose Amination or transamination To form non E.A.A. Via TCA cycle oxidized to CO2 & 99 H2O

urea
Amination of aketo acids

1) Amination or transamination To form non E.A.A. - ketoglutarate Pyruvate oxaloacetate Glu Ala Asp
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Glu - ketoglutarate
TCA cycle

oxaloacetate Asp
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2) Conversion to lipids or carbohydrates


glycogenic amino acid, such as : AlaArgAsp etc13 ketogenic amino acid such as:
leu lys (2)

glycogenic & ketogenic amino


acids such as : Ilu,Phe,Trp,Tye
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TCA cycle is the hinge

of metabolism of lipids ,
carbohydrates, proteins
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* *

*
*

*
*
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3) oxidation & provide energy 3. decarboxylation

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Non E.A.A -keto acids amines TCA cycle Conversion to lipids, carbohydrates

Amino acids

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Enzymes & coenzyme some important amines

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a.-amino butyric acid (GABA

formation

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enzyme
function

metabolic fate

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b. 5-hydroxy tryptamine or

( serotonin
formation

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function

c. taurine formation

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d. histamine

formation
function

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e. polyamines formation

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D. metabolism of individual

amino acids
1. one carbon units
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Concept
kinds

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the carrier of one carbon unites --------------THF

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the sources & conversion


NH2-CHCOOH +FH4

NH2-CHCH22+N5-CH3-FH4

CH22

COOH

SH

CH3
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function

one carbon units &


medicine
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2. metabolism of sulfur-

containing amono acids types

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Met

cystine

cysteine,Cys

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a.Met and Transfer of methyl group

S-adenosylmethionine
(SAM)
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Structure of SAM

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Function of SAM

methionine cycle B12 & methionine cycle


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B12

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3. metabolism of cystein &

cystine structure & characteristics

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Formation of GSH

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Catabolism of Cys
Cys

-NH2
pyruvate NH3 H2S

H2S

SO42-

Excrete in uria

PAPSactive sulfate

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The structure & function


of PAPS ( 3-phosphoadenosine-

5phosphosulfate
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4. metabolism of side

chain amino acids


Type: Val,Ile,Leu

Catabolic process
(extrahepatic tissue )
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ValIleLeu

-ketoacids

-ketoglutarate
Ala

Glu
pyruvate

NH3

Gln

Blood
liver

glyconeogenesis

urea

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5. metabolism of

aromatic amino acids


Type: Phe,Tyr,Trp

Catabolic process
(hepatic tissue)
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Catabolic process of Phe

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Albinism,

Phenylketonuria, (PKU) Alkaptonuria


BCAA/AAA 3:1
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