33. Metabolism of ammonia – generation, toxicity, ammonia detoxification: reductive amination of alpha-ketoglutarate, glutamine synthesis, role of ammoniagenesis in kidney. Urea cycle – regulation, metabolic disorders. Glucose-alanine cycle.

DETOXIFICATION OF AMMONIA

• Ammonia is highly toxic, particularly to the central nervous system, where it can lead to encephalopathy and coma.
• In the liver, excess ammonia is detoxified to prevent such toxicity.
• The urea cycle is the primary pathway for ammonia detoxification.

UREA CYCLE:

• It occurs mainly in the liver's periportal hepatocytes (the regions surrounding the hepatic arteries and portal veins).
• The cycle involves five enzymatic reactions that convert two molecules of ammonia and one molecule of carbon dioxide into one molecule of urea and one molecule of ornithine.
• The urea produced is then excreted via the kidneys in urine.

GLUTAMINE SYNTHESIS:

• Glutamine synthetase catalyzes the reaction between glutamate and ammonia to produce glutamine.
• Glutamine serves as a transport form of ammonia, carrying it safely to the kidneys for excretion or to other tissues for use in biosynthesis.

SYNTHESIS OF GLUTAMATE AND GLUTAMINE

Glutamate Synthesis:

• Glutamate is a non-essential amino acid synthesized from α-ketoglutarate, an intermediate of the citric acid cycle.
• Glutamate dehydrogenase catalyzes the reversible conversion of α-ketoglutarate and ammonia to glutamate.
• Glutamate is a central molecule in amino acid metabolism, serving as a precursor for the synthesis of other amino acids and as a neurotransmitter.