40. Fate of Amino Acid Nitrogen. Detoxification of Ammonia Through Biosynthesis of Urea - Urea Cycle
Covers how the nitrogen from amino acids is gathered and carried to the liver, starting with transamination to glutamate and oxidative deamination, then why free ammonia is toxic. It then walks through the urea cycle step by step, noting where each reaction occurs and the enzymes involved, including the aspartate-argininosuccinate link to the TCA cycle. The note also covers regulation by N-acetylglutamate, the ATP cost, and clinical hyperammonaemia with its causes, symptoms and treatments.
Topic 40 of 76 in the MU Pleven syllabus for Biochemistry (Medicine, Year 2). The free AceMed note covers it in 4 sections, about 387 words (3 min of reading), with 10 flashcards.
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Fate of Amino Acid Nitrogen. Detoxification of Ammonia Through Biosynthesis of Urea - Urea Cycle
Fate of Amino Acid Nitrogen
Detoxification of Ammonia
Urea Cycle (Ornithine Cycle)
Fate of Amino Acid Nitrogen
Amino acids are deaminated during metabolism → producing:
Carbon skeleton (→ used for energy / glucose / fat / ketones)
Amino group (NH₂) → must be safely removed because free ammonia (NH₃) is toxic, especially to the brain.
The first key step is Transamination:
Amino group from most amino acids is transferred to α-ketoglutarate.
This produces Glutamate, the main carrier of amino groups in the body.
Glutamate then undergoes Oxidative Deamination in the liver mitochondria:
Enzyme: Glutamate Dehydrogenase (GDH)
Reaction:
Glutamate → α-ketoglutarate + NH₃
This NH₃ enters the Urea Cycle.
In peripheral tissues, toxic ammonia is transported safely as:
Glutamine (via Glutamine Synthetase)
Alanine (via glucose-alanine cycle in muscles)
All excess nitrogen is ultimately converted to Urea in the liver and excreted by the kidneys.
Detoxification of Ammonia
Ammonia is toxic because:
It disrupts the TCA cycle in neurons.
It causes brain edema and confusion.
High levels → hepatic encephalopathy.
Therefore, ammonia must be converted to a non-toxic, water-soluble compound → Urea.
Liver is the only organ that performs the complete Urea Cycle.
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