Biochemistry · MU Pleven

41. Other Ways of Detoxification of Ammonia: Reductive Amination, Oxidative Deamination of Amino Acids, The Role Of Glutamate, Biosynthesis of Glutamine. The Role of Renal Glutaminase.

Explains how the body keeps ammonia from building up by routing it into safer forms. It takes reductive amination via glutamate dehydrogenase, oxidative deamination that releases ammonia for urea synthesis, and the central role of glutamate as an amino group carrier. It then covers glutamine synthesis as a non-toxic transport form and the renal glutaminase system that excretes ammonium to help control acid-base balance, ending with brief clinical takeaways on hyperammonaemia and acidosis.

Inside: 3 sections · 5 labelled pictures · 20 flashcards · 3 min

Topic 41 of 76 in the MU Pleven syllabus for Biochemistry (Medicine, Year 2). The free AceMed note covers it in 3 sections, about 358 words (3 min of reading), with 20 flashcards.

In this note

  1. Other Ways of Detoxification of Ammonia: Reductive Amination, Oxidative Deamination of Amino Acids, The Role Of Glutamate, Biosynthesis of Glutamine.
  2. Other Ways of Detoxification of Ammonia
  3. Key Clinical Takeaways

Other Ways of Detoxification of Ammonia

  • The body cannot allow free ammonia (NH₃) to accumulate, because it is highly neurotoxic.
  • So ammonia is re-routed, chemically modified, and transported in safe forms.
  • The major systems involved:
  • Reductive amination
  • Oxidative deamination
  • Transamination and role of glutamate
  • Formation of glutamine
  • Renal glutaminase system

1. Reductive Amination

  • Mediated by Glutamate Dehydrogenase (GDH) in mitochondria.
  • Reaction:
  • α-Ketoglutarate + NH₃ + NADPH → Glutamate.
  • This reaction captures free ammonia and stores it safely as glutamate.
  • Occurs mostly in the liver and brain.
  • Helps prevent ammonia accumulation.

2. Oxidative Deamination of Amino Acids

  • Also catalyzed primarily by Glutamate Dehydrogenase (GDH).
  • Reaction:
  • Glutamate → α-ketoglutarate + NH₃.
  • This mainly occurs in the liver mitochondria.
  • It frees ammonia only when there is a need to convert it into urea.
  • Thus oxidative deamination provides NH₃ for the urea cycle.

3. The Central Role of Glutamate

  • Glutamate is the main “traffic hub” of amino group metabolism.
  • It is formed by transamination of most amino acids.
  • It can:
  • Accept amino groups (NH₂ acceptor)
  • Donate amino groups (NH₂ donor)
  • Glutamate transports ammonia safely within cells, preventing toxic free NH₃ buildup.
  • It is the direct precursor of glutamine.

4. Biosynthesis of Glutamine (Ammonia Storage and Transport Form)

  • Enzyme: Glutamine Synthetase (cytosol).
  • Reaction:
  • Glutamate + NH₃ + ATP → Glutamine.
  • Glutamine is the main “nontoxic carrier of ammonia” in the blood.
  • It is transported from:
  • Muscle → Liver
  • Muscle → Kidney
  • Brain → Blood
  • Glutamine is used to remove ammonia safely from peripheral tissues.

5. The Role of Renal Glutaminase

  • In the kidney, enzyme Glutaminase converts Glutamine → Glutamate + NH₃.
  • This released ammonia is used to buffer and excrete acids:
  • NH₃ binds H⁺ in renal tubules → NH₄⁺ (ammonium) → excreted.
  • This is a major mechanism for maintaining acid–base balance.
  • During metabolic acidosis, renal glutaminase activity increases dramatically.
  • This leads to:
  • More NH₄⁺ excretion
  • More bicarbonate (HCO₃⁻) retention
  • Thus kidneys help control blood pH while removing nitrogen waste.

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