ammoniagenese

Ammoniagenese, or ammoniagenesis, is the metabolic production of ammonia (NH3) and its ion form ammonium (NH4+) as a byproduct of amino acid catabolism. In humans, the primary site is the proximal tubules of the kidney, with additional contribution from other tissues and, to a lesser extent, the liver. The process plays a dual role in nitrogen metabolism and in maintaining acid–base balance, because the ammonia produced can bind hydrogen ions to form ammonium, which is excreted in urine.

A central mechanism involves the deamination of glutamine. Glutamine is taken up by renal tubular cells and converted by glutaminase to glutamate and NH3. Glutamate can then be further deaminated to alpha-ketoglutarate, releasing a second NH3. The resulting ammonia diffuses into the tubular lumen, where it combines with secreted protons to form NH4+, which is excreted in the urine. This excretion helps eliminate acid from the body and provides a mechanism for net acid wasting.

Regulation of ammoniagenesis is closely tied to the body's acid–base status. Metabolic acidosis stimulates renal ammoniagenesis to increase ammonium production and urinary acid excretion. The rate depends on glutamine availability, renal function, and, to a broader extent, hormonal and energetic factors that influence renal metabolism.

Clinical relevance lies in its role in acid–base disorders. In chronic kidney disease, reduced ammonium excretion can contribute to metabolic acidosis. Conversely, disorders that affect glutamine metabolism or renal ammoniagenesis can alter the body's ability to handle acid loads. Measuring urinary ammonium excretion can aid in assessing renal acid-base handling.