A lucid presentation on Metabolism of Glutamate , Glutamine ,Aspartate & Asparagine for MBBS, BDS , B. Pharm & Biotechnology students to facilitate self-study.

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

2. FORMATION AND FATE OF
GLUTAMATE & GLUTAMINE

3. Fate/ functions of Glutamate & Glutamine
Fate 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

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

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

6. 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 )

7. Synthesis of GABA from Glutamate /Glutamine

8. Comparison of synthesis of Glutamate & Glutamine
Synthesis of Glutamate Synthesis of Glutamine
Reaction α KGA +NH3 +NAD/NADP +H2O
↔ Glutamate
Glutamate + ATP+ Mg⁺ +
NH3Glutamine + 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

9. Glutamate & Glutamine
1) 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

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

11. Aspartate & Asparagine

12. Aspartate & Asparagine
1) Non essential amino acids
2) Glucogenic amino acids

13. TRANSAMINATION-Aspartate & Glutamate

14. Functions of Aspartate
Proteins purines
Glucose pyrimidine
Urea
Aspartate

15. 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

16. Aspartate & Asparagine
Donation of amino group in urea synthesis by Aspartate

17. Aspartate as source of Nitrogen atom in Urea molecule

18. Fate of Amino acids in Human body

19. Transport of amino group :Glucose & Alanine cycle
FATE OF PYRUVATE –
DERIVED FROM
OAA(ASP ON
TRANSAMINATION
YEILDS OAA )

20. Aspartate & Asparagine :Linking OF TCA with Urea cycle

21. Aspartate links TCA cycle with Urea cycle

22. 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

23. Malate –Aspartate shuttle
NADH is transported to mitochondria in form of MALATE
OAA is transported to cytosol in form of Aspartate

24. OAA -LINKING OF CARBOHYDRATE METABOLISM WITH PROTEIN METABOLISM

25. Linking of
Aspartate ,
Glutamine
&
Asparagine

26. Synthesis of Asparagine catalyzed by Asparagine synthetase

27. Role of Asparaginase in synthesis of Aspartate