Date post: | 25-Jan-2017 |
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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