ornithine

Ornithine is a non-proteinogenic amino acid that plays a central role in nitrogen metabolism. It is not incorporated into proteins but functions as a key intermediate in the urea cycle and as a precursor in other metabolic pathways.

In the urea cycle, ornithine is a mitochondrial substrate that reacts with carbamoyl phosphate to form citrulline, a reaction catalyzed by ornithine transcarbamylase. Citulline then enters the cytosol, where it combines with aspartate to form argininosuccinate (via argininosuccinate synthetase). Arginiosuccinate lyase cleaves this to arginine and fumarate; arginase then hydrolyzes arginine to yield urea and ornithine, which can re-enter the mitochondria to continue the cycle. Thus, ornithine cycles between mitochondria and cytosol as part of nitrogen disposal.

Ornithine is also a precursor in polyamine biosynthesis. Ornithine decarboxylase converts it to putrescine, which is further converted into spermidine and spermine, polyamines involved in cell growth and differentiation.

Clinically, disorders affecting ornithine handling in the urea cycle can lead to hyperammonemia. Conditions such as ornithine transcarbamylase deficiency and hyperornithinemia-hyperammonemia-homocitrullinuria syndrome reflect disruptions in ornithine transport or metabolism and can present with elevated ammonia levels.

Dietary ornithine is not considered essential, as the body can synthesize it. It is found in proteins and is also studied in supplement form (for example, ornithine alpha-ketoglutarate) in various contexts, though evidence for specific benefits varies.