Metabolism of Glutamate , Glutamine ,Aspartate & Asparagine Dr Rohini C Sane

FORMATION AND FATE OF

GLUTAMATE & GLUTAMINE

Fate/ functions of Glutamate & GlutamineFate of Glutamate Fate of Glutamine

Glutathione Transport & storage of ammonia

N acetyl Glutamate ( NAG ) Donor of nitrogen for purine & pyrimidine

Clotting factor ( II ,VII , IX , X ) Chief source of ammonia in kidney

GABA ( GAMMA AMINO BUTYRIC ACID )δ Glutamate decarboxylase- PLP dependent

Inhibitor neurotransmitters in brain ↓ transmission signals Opens chloride channels / ↑ permeability of post synaptic membrane

Acid base balance –during acidosis production of ammonia by kidney increases

↓ GABA convulsion Detoxification by conjugation

Vitamin B12 deficiency ↓ GABA neuronal hyper excitability convulsion

Entry of Glutamate into TCA CYCLE via Alpha –Ketoglutarate(α KGA )

Inter relation of Alpha –Ketoglutarate(α KGA ) ,Glutamate & Glutamine

Role of Glutamine in human body • Glutamine synthesis in Liver /Brain /muscles ( mitochondria )

Glutamate synthtase

• Glutamate + NH3 +ATP +Mg⁺ Glutamine + ADP

• Concentration of Serum Glutamine –0.8 mg /dl (amino acid with highest Concentration )

• Glutamine =Store house of ammonia

• Glutamine =Transport of ammonia

• Glutamine =Removable of ammonia from brain

• Glutamine= freely diffusible in tissue

Glutaminase

• Glutamine Glutamate + NH3 (deamination in kidney & intestine )

Synthesis of GABA from Glutamate /Glutamine

Comparison of synthesis of Glutamate & GlutamineSynthesis of Glutamate Synthesis of Glutamine

Reaction α KGA +NH3 +NAD/NADP +H2O ↔ Glutamate

Glutamate + ATP+ Mg⁺ + NH3Glutamine + H2O

ENZYME Glutamate dehydrogenase (GDH ) Glutamine synthtase

Site of synthesis Liver ,kidney Mitochondria of liver ,brain ,muscles

Type of reaction Reversible/bidirectional irreversible/unidirectional

Activity of enzyme Increases with protein diet decreased by enzyme Glutaminase( ACTIVE IN KIDNEY, MUSCLES ) Glutamine Glutamate + NH3

Allosteric inhibitors of enzyme

GTP ,ATP

Allosteric activators of enzyme

GDP, ADP

Glutamate & Glutamine1) Non essential amino acids

2) Glucogenic amino acids

3) Final transfer of NH2 for urea synthesis

4) Glutamate links Metabolism of Histidine ,Proline &Arginine

Histidine Proline Arginine

↘ ↓ ↙Glutamate

↓

Glutamine

Clinical Significance of GABA-GAMMA-AMINO BUTYRIC ACID DERIVED FROM GLUTAMATE

Aspartate & Asparagine

Aspartate & Asparagine

1) Non essential amino acids

2) Glucogenic amino acids

TRANSAMINATION-Aspartate & Glutamate

Functions of Aspartate

Proteins purines

Glucose pyrimidine

Urea

Aspartate

Functions of Aspartate & Asparagine

Functions

1. donation of amino group in urea synthesis

2. Linking OF TCA with Urea cycle

3. synthesis of purines nitrogen at N1 of purine ring is contributed by Aspartate

4. N2 ,C4,C5,C6 OF Pyrimidine is contributed by Aspartate

5. Malate –Aspartate shuttle

Aspartate & Asparagine

Donation of amino group in urea synthesis by Aspartate

Aspartate as source of Nitrogen atom in Urea molecule

Fate of Amino acids in Human body

Transport of amino group :Glucose & Alanine cycle

FATE OF PYRUVATE –DERIVED FROM OAA(ASP ON TRANSAMINATION YEILDS OAA )

Aspartate & Asparagine :Linking OF TCA with Urea cycle

Aspartate links TCA cycle with Urea cycle

Role of of Glutamine & Aspartate in synthesis of pyrimidine base & purine nucleus

N2 ,C4,C5,C6 OF Pyrimidine by Aspartate N1 of purine ring by Aspartate

Malate –Aspartate shuttleNADH is transported to mitochondria in form of MALATEOAA is transported to cytosol in form of Aspartate

OAA -LINKING OF CARBOHYDRATE METABOLISM WITH PROTEIN METABOLISM

Linking of Aspartate ,Glutamine& Asparagine

Synthesis of Asparagine catalyzed by Asparagine synthetase

Role of Asparaginase in synthesis of Aspartate