Ornithine is an intermediate nonprotein-forming amino acid of the urea cycle. Arginine is converted to ornithine via the arginase enzyme, with urea as a byproduct. Ornithine combined with carbamoyl phosphate is then converted into citrulline via the ornithine transcarbamylase (OTC) enzyme. The contribution of carbamoyl phosphate results from the metabolism of ammonia by the enzyme carbamoyl phosphate synthase, and if this magnesium-dependent process is impaired, ammonia buildup, or hyperammonemia can occur.
Ornithine can also form polyamines including putrescine via the ornithine decarboxylase (ODC) enzyme, which requires pyridoxal-5-phosphate (vitamin B6) as a cofactor. Putrescine and other polyamines are crucial to the growth and proliferation of cells. Ornithine forms glutamate via ornithine aminotransferase (OAT), requiring pyridoxine (vitamin B6) as a cofactor. OAT deficiency is a rare congenital disorder characterized by gyrate atrophy of the choroid and retina, and is treated with vitamin B6 to prevent vision loss.
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Low protein intake can result in low levels of urea cycle intermediates. Low ornithine may be of no clinical consequence; evaluate other urea cycle intermediates and metabolites. A nonspecific finding of decreased plasma ornithine and arginine may be seen with OTC deficiency; this would be accompanied by hyperammonemia and elevated orotic acid, plasma glutamine and alanine.
Elevations of ornithine may be due to a limitation in the cofactors associated with metabolism including vitamin B6 and magnesium.
Elevations may also result from supplementation of citrulline or ornithine. Administration of thiamine (vitamin B1) lowered elevated ornithine, as well as other amino acids in thiamine deficiency. OTC deficiency resulting in hyperammonemia is an inborn error of metabolism and is the most common of the inborn errors of the urea cycle. While most inborn errors present during the neonatal period or early childhood, some can have a later onset in adulthood, including OTC deficiency. It is characterized by elevated ammonia and orotic acid (an organic acid) due to the metabolic block.
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