Q.21 Identify the enzyme that catalyzes the following reaction

α-Ketoglutarate + NADH + NH₄⁺ + H⁺
→  Glutamate + NAD⁺ + H₂O

• (A) Glutamate synthetase
• (B) Glutamate oxoglutarate aminotransferase
• (C) Glutamate dehydrogenase
• (D) α-ketoglutarate deaminase
  

  Glutamate Dehydrogenase: α-Ketoglutarate to Glutamate Reaction Enzyme

  Glutamate dehydrogenase catalyzes the reductive amination of α-ketoglutarate to glutamate using NADH. This MCQ tests identification of the correct enzyme for this nitrogen assimilation reaction.

  Correct Answer: (C) Glutamate Dehydrogenase

  Glutamate dehydrogenase (GDH) catalyzes the reversible reaction: α-Ketoglutarate + NADH + NH₄⁺ + H⁺ → Glutamate + NAD⁺ + H₂O. This mitochondrial enzyme uses NADH/NADPH as cofactors for ammonia assimilation into glutamate, a key step in nitrogen metabolism.

  Reaction Mechanism

  GDH facilitates reductive amination where:

  • α-Ketoglutarate’s keto group accepts ammonia (NH₄⁺)

  • NADH provides hydride (H⁻) for reduction

  • Result: L-glutamate formation with NAD⁺ regeneration

  Overall reaction:
  α-Ketoglutarate + NH₄⁺ + NADH + H⁺ → Glutamate + NAD⁺ + H₂O

  Detailed Option Analysis

  Option	Enzyme Name	Accuracy	Explanation
  (A)	Glutamate synthetase	Incorrect	Catalyzes glutamine synthesis: Glutamate + NH₄⁺ + ATP → Glutamine + ADP + Pi + H⁺. ATP-dependent, no NADH involvement. ​
  (B)	Glutamate oxoglutarate aminotransferase	Incorrect	Refers to glutamate-oxoglutarate transaminase (ALT/AST). Transfers amino groups between glutamate ↔ α-ketoglutarate using other amino acids as donors. No NH₄⁺ or NADH used.
  (C)	Glutamate dehydrogenase	Correct	Precisely matches reaction. Uses NADH/NADPH for direct NH₄⁺ incorporation into α-ketoglutarate forming glutamate.
  (D)	α-Ketoglutarate deaminase	Incorrect	Non-existent enzyme. Deaminases remove NH₂ groups; this reaction adds ammonia (amination).

  Biochemical Context

  Location: Mitochondrial matrix (primarily GDH1/GDH2 isoforms)​
  Cofactors: NAD(P)H/NAD(P)⁺ (reversible reaction)
  Regulation: Allosteric control by GTP (inhibitor), ADP/leucine (activators)

  Biotechnology Applications

  • Nitrogen assimilation: Primary pathway for NH₄⁺ incorporation into amino acids

  • Ammonia detoxification: Converts toxic NH₄⁺ to glutamate in liver/kidney

  • Glutamate production: Industrial biosynthesis using Corynebacterium/cyanobacteria

  • Exam tip: GDH = direct NH₄⁺ → glutamate (NADH-dependent). GS/GOGAT cycle = indirect (ATP-dependent)

  Key Memory Point

  GDH reaction direction matters:

  text

  Forward (ammonia assimilation): α-KG + NH₄⁺ + NADH → Glutamate + NAD⁺
Reverse (oxidative deamination): Glutamate + NAD⁺ → α-KG + NH₄⁺ + NADH


  Memorize: Only glutamate dehydrogenase directly uses NH₄⁺ + NADH with α-ketoglutarate.