*

Arrange by : Darson; Dea Apriyani; Elfira Bauzir; Farhati Mardhiyah

*Overview of Amino Acid Catabolism:

Interorgan Relationships

*Overview of Amino Acid Catabolism:

Interorgan Relationships

Intestine Dietary amino acids absorbed Utilizes glutamine and asparagine as energy sources Releases CO2, ammonium, alanine, citrulline as endproducts Utilizes glutamine during fasting for energy Dietary amino acids and catabolites released to portal blood

*Overview of Amino Acid Catabolism:

Interorgan Relationships

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 general circulation

*Overview of Amino Acid Catabolism:

Interorgan Relationships

Skeletal Muscle Muscle protein synthesis Catabolism of BCAA Amino groups transported away as alanine and 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)

in Amino Acid Metabolism

*Vitamin-Coenzymes

Vitamin B-6 (pyridoxal phosphate)

Folic acid (tetrahydrofolate)

Vitamin B-12

*Vitamin-Coenzymes in Amino Acid

Metabolism

Vitamin B-12 Catabolism of BCAA Methyl-malonyl CoA mutase

in Amino Acid Metabolism

*Vitamin-Coenzymes

Vitamin B-6 : pyridoxal phosphate Enzymes that bind amino acids use PLP as coenzyme for binding Transaminases Amino acid decarboxylases Amino acid deaminases

in Amino Acid Metabolism

*Vitamin-Coenzymes

Folacin: Tetrahydrofolate (THF) Carrier of single carbons Donor & receptor Glycine and serine Tryptophan degradation Histidine degradation Purine and pyrimidine synthesis

*Transamination
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
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
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

* Biosynthesis of Amino Acid: Transamination

Reactions
Example of a Transaminase reaction:
COO COO CH2 HC NH3+

COO COO CH2 CH2 CH2 O

CH2 CH2

HC

NH3+

Aspartate donates its amino group, becoming the a-keto acid oxaloacetate. a-Ketoglutarate accepts the amino group, becoming the amino acid glutamate.

COO

COO

COO

COO

aspartate -ketoglutarate oxaloacetate glutamate

Aminotransferase (Transaminase)

*Transamination
Pyridoxal phosphate and transamination

Mechanism of transamination reaction

*
* In the cytosoL amino
Transamination (cytosol)

groups from most amino acids are transferred to -ketoglutarate to form glutamate, which enters mitochondria and gives up its amino group to form NH4+. generated in most other tissues is converted to the amide nitrogen of glutamine, which passes to the liver, then into liver mitochondria.
17

Deamination (Mitochondria)

* Excess ammonia

elimination of amino group from amino acid with ammonia formation

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

- reduction, - hydrolytic, and - intramolecular

Reduction deamination:
R-CH(NH2)-COOH + 2H+ R-CH2-COOH + NH3

amino acid

fatty acid

Hydrolytic deamination:
R-CH(NH2)-COOH + H2O R-CH(OH)-COOH + NH3

amino acid

hydroxyacid

Intramolecular deamination:
R-CH(NH2)-COOH R-CH-CH-COOH + NH3

amino acid

unsaturated fatty acid

D E A M I N A T

I O N

L-Glutamate dehydrogenase plays a central role in amino acid deamination

In most organisms glutamate is the only amino acid that has active dehydrogenase Present in both the cytosol and mitochondria of the liver

Glutamate Releases Its Amino Group as Ammonia in the Liver

The -ketoglutarate formed from glutamate deamination can be used in the citric acid cycle and for glucoseSynthesis The fate of the NH4 produced by any of these deamination Processes. In the liver the ammonia from all sources is disposed of by urea synthesis.

disposed of by urea synthesis.

Glutamine metabolism

*
Six Amino Acids Are Degraded to Pyruvate alanine, tryptophan, cysteine, serine, glycine, and threonine 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, and histidine

Four Amino Acids Are Converted to Succinyl-CoA methionine, isoleucine, threonine,and valine

Two amino acids are converte to oxaloacetate Asparagine and aspartate

*Alanine yields pyruvate directly on transamination with

ketoglutarate
COO CH2 CH3 HC NH3+ CH2 CH3 O C O COO CH2 CH2

HC

NH3+

COO

COO

COO

COO

alanine

pyruvate glutamate Aminotransferase (Transaminase)

-ketoglutarate

pyruvate Threonine -ketobutyrate

*
Succinyl CoA

Inter conversion of serine and glycine Serine can be converted to glycine and N5, N10-methylenetetrahydorfolate or to pyruvateby serine dehydratase.

*
The major route of cysteine degradation most likely starts by the oxidation of cysteine to 3-sulfinoalanine. The conversion of L-cysteine to 3sulfinoalanine (L-cysteine sulfinic acid) forms a branch point. In one route, 3sulfinoalanine is transaminated by 3sulfinoalanine aminotransferase to 3sulfinyl-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 pyruvate decarboxylation to acetyl CoA to acetylCoA, which enters the TCA cycle I (prokaryotic).

*
Tryptophan breakdown is the most complex of all the
pathways of aminoacid catabolism in animal tissues; portions of tryptophan (four of its carbons) yield acetyl-CoA via acetoacetyl- CoA.

Some of the intermediates in tryptophan catabolism

are precursors for the synthesis of other biomolecules, including nicotinate, a precursor of NADand NADP in animals; serotonin, a neurotransmitter in vertebrates; and indoleacetate, a growth factor in plants.

*
Transamination of tyrosine to phydroxyphenylpyruvate is catalyzed by tyrosine -ketoglutarate transaminase (tyrosine aminotransferase).

P-hydroxyphenylpyruvate forms homogentisate catalysed by phydroxyphenylpyruvate dioxygenase where ascorbic acid is the reductant.

*
Lysine is an entirely ketogenic amino acid.
There is an initial transamination of the -amino group
which requires -ketoglutarate as the acceptor and cosubstrate.

The resulting compound is -ketoadipate which forms

acetoacetyl CoA.

Figure 26-23 The pathway of lysine degradation in mammalian liver.

Saccharopine dehydrogenase (NADP+, Lys forming) Saccharopine dehydrogenase (NAD+, Glu forming) Aminoadipate semialdehyde dehydrogenase Aminoadipate aminotransferase (PLP) -keto acid dehydrogenase

1. 2. 3. 4. 5.

6.
7. 8. 9.

Glutaryl-CoA dehydrogenase
Decarboxylase Enoyl-CoA hydratase -hydroxyacyl-CoA dehydrogenase

10.
11.

HMG-CoA synthase
HMG-CoA lyase

*
Leucine and isoleucine also give acetyl CoA.
More details will be explained in branched chain amino acid catabolism.