protein metabolism dea farha fira darson fine

7/29/2019 PROTEIN METABOLISM Dea Farha Fira Darson Fine

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Arrange by :

Darson; Dea Apriyani; Elfira Bauzir; Farhati Mardhiyah

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*Overview of Amino Acid Catabolism:

Interorgan Relationships


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Intestine

Dietary amino acids absorbed

Utilizes glutamine and asparagine asenergy sources

Releases CO2, ammonium, alanine,citrulline as endproducts

Utilizes glutamine during fasting forenergy

Dietary amino acids and catabolitesreleased to portal blood


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Liver

Synthesis of liver and plasma proteins

Catabolism of amino acids Gluconeogenesis

Ketogenesis

Branched chain amino acids not

catabolized Urea synthesis

Amino acids released into generalcirculation


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Skeletal Muscle

Muscle protein synthesis

Catabolism of BCAA

Amino groups transported away as alanineand glutamine (50% of AA released)

Alanine to liver for gluconeogenesis

Glutamine to kidneys

Kidney Glutamine metabolized to a-KG + NH4

a-KG for gluconeogenesis

NH4 excreted or used for urea cycle

(arginine synthesis)


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*Vitamin-Coenzymes

in Amino Acid Metabolism

Vitamin B-6 (pyridoxal phosphate)

Folic acid (tetrahydrofolate) Vitamin B-12


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*Vitamin-Coenzymes in Amino Acid

Metabolism

Vitamin B-12

Catabolism of BCAA

Methyl-malonyl CoA mutase


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*Vitamin-Coenzymes


Vitamin B-6 : pyridoxal

phosphate

Enzymes that bind aminoacids use PLP as

coenzyme for binding

Transaminases

Amino acid

decarboxylases

Amino acid deaminases


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*Vitamin-Coenzymes


Folacin: Tetrahydrofolate(THF)

Carrier of single carbons

Donor & receptor

Glycine and serine

Tryptophan degradation

Histidine degradation Purine and pyrimidine

synthesis


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Transamination is a enzimatic reaction that

moving -amino groups into -carbon in -

ketoglutarate.

Released -keto acid and L-glutamate.

Occur: cytosol

Function: to release and collect only one type of

amino acid, that is L-glutamate.

L-glutamate is source of oxidative deamination.

*Transamination


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The first step in the catabolism of most amino acids is

removal of a-amino groups by enzymes transaminases or

aminotransferases.

All aminotransferases have the same prostethic group

and the same reaction mechanism.

The prostethic group is pyridoxal phosphate (PLP), the

coenzyme form of pyridoxine (vitamin B6).

*Transamination

*


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*Transamination

Amino groups can be

removed by

transamination

In liver cytosol, amino

groups are dumped to

-KG, forming

glutamate.

Transaminases (aka

aminotransferases)

require pyridoxal

phosphate cofactor.

Removal of amino

group via

transamination


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*Biosynthesis of Amino Acid: Transamination

Reactions

Example of aTransaminase reaction:

Aspartate donates its

amino group, becomingthe a-keto acidoxaloacetate.

a-Ketoglutarate accepts

the amino group,becoming the amino acidglutamate.

aspartate -ketoglutarate oxaloacetate glutamate

Aminotransferase (Transaminase)

COO

CH2

CH2

C

COO

O

COO

CH2

HC

COO

NH3+

COO

CH2

CH2

HC

COO

NH3+

COO

CH2

C

COO

O+ +

*


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*Transamination

Pyridoxal phosphate and transamination


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Mechanism of

transamination

reaction


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*In the cytosoL amino

groups from most aminoacids are transferred to

-ketoglutarate to form

glutamate, which enters

mitochondria and gives up

its amino group to form

NH4+.

*Excess ammonia

generated in most other

tissues is converted tothe amide nitrogen of

glutamine, which passes

to the liver, then into

liver mitochondria.17

Transamination

(cytosol)

Deamination

(Mitochondria)


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Four types of deamination:- oxidative(the most important for higher animals),- reduction,- hydrolytic, and- intramolecular

elimination of amino groupfrom amino acid with

ammonia formation


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Reduction deamination:

R-CH(NH2)-COOH + 2H+ R-CH2-COOH + NH3amino acid fatty acid

Hydrolytic deamination:

R-CH(NH2)-COOH + H2O R-CH(OH)-COOH + NH3amino acid hydroxyacid

Intramolecular deamination:

R-CH(NH2)-COOH R-CH-CH-COOH + NH3amino acid unsaturated fatty acid


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L-Glutamate dehydrogenaseplays a central role in amino aciddeamination

In most organisms glutamate is the only amino acid that hasactive dehydrogenase

Present in both the cytosol and mitochondria of the liver

O X I D A T I V E D E A M I N A T I O N


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Glutamate Releases Its Amino Groupas Ammonia in the Liver

The -ketoglutarate formed fromglutamate deamination can beused in the citric acid cycle andfor glucoseSynthesis

The fate of the NH4 produced by anyof these deamination Processes. Inthe liver the ammonia from allsources is disposed of by ureasynthesis.


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Glutaminemetabolism

disposed of byurea synthesis.


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Six Amino Acids Are Degraded to Pyruvate

alanine, tryptophan, cysteine, serine, glycine, andthreonine

Seven Amino Acids Are Degraded to Acetyl-CoA

tryptophan, lysine, phenylalanine, tyrosine, leucine,isoleucine, and threonine

Five Amino Acids Are Converted to Ketoglutarate

proline, glutamate, glutamine, arginine, andhistidine

Four Amino Acids Are Converted to Succinyl-CoA

methionine, isoleucine, threonine,and valine

Two amino acids are converte to oxaloacetate

Asparagine and aspartate


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*Alanine yields pyruvate directly on transamination withketoglutarate

alanine -ketoglutarate pyruvate glutamate Aminotransferase (Transaminase)

COO

CH2

CH2

C

COO

O

CH3

HC

COO

NH3+

COO

CH2

CH2

HC

COO

NH3+

CH3

C

COO

O+ +


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Threonine

pyruvate

-ketobutyrate Succinyl CoA


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Inter conversion of serine and glycine

Serine can be converted to glycine and

N5, N10-methylenetetrahydorfolate or topyruvateby serine dehydratase.


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The major route of cysteine degradationmost likely starts by the oxidation of

cysteine to 3-sulfinoalanine. The

conversion of L-cysteine to 3-

sulfinoalanine (L-cysteine sulfinic acid)

forms a branch point. In one route, 3-

sulfinoalanine is transaminated by 3-sulfinoalanine aminotransferase to 3-

sulfinyl-pyruvate, which spontaneously

degrades to pyruvate and sulfite. Sulfite is

oxidized by sulfite oxidase to sulfate,

which is excreted in the urine, and

pyruvate is converted by pyruvatedecarboxylation to acetyl CoA to acetyl-

CoA, which enters the TCA cycle I

(prokaryotic).
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Tryptophan breakdown is the most complex of all thepathways of aminoacid catabolism in animal tissues;portions of tryptophan (four of its carbons) yieldacetyl-CoA via acetoacetyl- CoA.

Some of the intermediates in tryptophan catabolismare precursors for the synthesis of other biomolecules,including nicotinate, a precursor of NADand NADP inanimals; serotonin, a neurotransmitter in vertebrates;and indoleacetate, a growth factor in plants.


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Transamination of tyrosine to p-hydroxyphenylpyruvate is catalyzed bytyrosine -ketoglutarate transaminase

(tyrosine aminotransferase).

P-hydroxyphenylpyruvate formshomogentisate catalysed by p-

hydroxyphenylpyruvate dioxygenasewhere ascorbic acid is the reductant.


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Lysine is an entirely ketogenic amino acid.

There is an initial transamination of the -amino groupwhich requires -ketoglutarate as the acceptor and

cosubstrate.

The resulting compound is -ketoadipate which formsacetoacetyl CoA.

* Figure 26-23 The


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1. Saccharopine dehydrogenase

(NADP+, Lys forming)

2. Saccharopine dehydrogenase

(NAD+, Glu forming)

3. Aminoadipate semialdehyde

dehydrogenase

4. Aminoadipate aminotransferase

(PLP)

5. -keto acid dehydrogenase

6. Glutaryl-CoA dehydrogenase

7. Decarboxylase

8. Enoyl-CoA hydratase

9. -hydroxyacyl-CoA

dehydrogenase

10. HMG-CoA synthase

11. HMG-CoA lyase

gpathway of lysine

degradation inmammalian liver.


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Leucine and isoleucine also give acetyl CoA. Moredetails will be explained in branched chain amino acid

catabolism.

protein metabolism dea farha fira darson fine

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