Transamination & DeaminationDr Rohini C Sane

Transamination Definition : Transfer of amino group to keto acids

1. Transaminases ( amino transferase) 2. amino acids 1+ α keto acids 1↔ amino acids 2+ α keto acids 2

3. Pyridoxal phosphate –cofactor derived from vitamin B6

4. No free ammonia 5. Reversible ( catabolism /anabolism )

6. Excess amino acids derived used for energy generation

7. Synthesis of non essential amino acids /redistribution of amino group 8. Lysine / Threonine/ Proline / hydroxyl proline exception to rule

9. Production of non essential amino acids

10 . α amino acids / δ amino acids ( Ornithine ) undergo transamination 11. Clinical significance : SGOT ↑ in AMI & SGPT ↑IN Liver diseases

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TRANSAMINATION

ROLE OF PYRIDOXAL PHOSPHATE IN TRANSAMINATION

TRANSAMINATION

TRANSAMINATION BY SGPT

TRANSAMINATION BY SGOT

Mechanism of Transamination

• CHO group of PLP forms Schiff base (1 )with Lys residue of transaminase with imine linkage Lys displaced by amino acid to form Schiff base (2 )

Deamination • Definition : Removal of amino group as ammonia which is utilized for urea

formation & carbon skeletons are used for formation the keto acids .

• Transamination & Deamination take place simultaneously.(Trans deamination )

Fate of carbon skeletons of amino acids

1. Oxidation TCA Energy

2. Synthesis of Glucose

3. Formation of lipids ( fatty acids & ketone bodies )

4. Synthesis of non essential amino acids

Entry points of amino acids in TCA cycle

Amino acids Entry points of amino acids in TCA cycle

Ala ,Gly , Cyst ,Ser, Thr Pyruvate, Acetyl CoA

Phe, Tyr ,Trp ,Leu ,Lys ,Ile Aceto- acetate

Asn, Asp Oxaloacetate

His, Arg, Pro ,Glu ,Gln α KGA

Met, Val ,Ile,Thr Succinyl Co A

Oxidative Deamination

1. Site : kidney & Liver ( mitochondria )

2. Catalyzed by Glutamate dehydrogenase ( GDH )

Purpose :/significance

a) Ammonia utilized for Urea formation

b) α keto acids for energy

c) Glutamate accepts amino group from amino acids ( Transamination )

d) Glutamate –is collection center for amino group oxidative deamination

Oxidative deamination by Glutamate dehydrogenase (GDH )

TCA CYCLE

Regulation of Glutamate dehydrogenase (GDH )1. protein rich diet ↑ GDH Glutamate concentration increases in liver

concentration of α KGA increases concentration of NH3 increases

TCA increases ( ↑ ATP ) Urea production increases

2. Steroid hormones / Thyroid hormones ↓ GDH

3. Cellular energy low Glutamate ↓ oxidative deamination induced↑ GDH

4.Allosteric Regulation of Glutamate dehydrogenase (GDH )

Allosteric inhibitors Allosteric activators

GTP GDP

ATP ADP

Glutathione

GABA

N ACETYL GLUTAMATE (NAG )

Oxidative deamination of Amino acid oxidases

Reduction of O2 to H2O2 hydrolysis to water

Oxidative deamination by Amino acid oxidases• Activity of L -amino acid oxidases low

• Activity of D amino acid oxidase high ( liver & kidney )

• L -amino acid oxidases dose not act on Glycine & di carboxylic acids

• L -amino acid oxidases dose appear to play significant role in amino acid metabolism.

Oxidative deamination by Amino acid oxidases

D - amino acids (dietary/ plants / micro organisms /mammals )

H2O FAD

NH4 FADH2

Energy ←α Keto acids glucose /fat conversion of unnatural

L amino acid Transaminase D amino acid L amino acid

α Keto acids

L –amino acid

Metabolism

Non- oxidative deamination• Amino acids deaminated to liberate ammonia without undergoing

oxidation

Serine Dehydratase

Threonine respective α keto acids

Homoserine PLP

( hydroxy amino acid ) NH3

Non- oxidative deamination by De sulphhydratases

cysteine Deamination

Homocystein PYRUVATE

Desulphhydration

NH3 + H2S

Non- oxidative deamination Histidine

Deamination

Histidine Urocanate

Histadase

NH3