Ornithine aminotransferase

Ornithine aminotransferase (OAT) is an enzyme that plays a crucial role in the metabolism of amino acids in the liver. It catalyzes the reversible transfer of an amino group from ornithine to alpha-ketoglutarate, producing glutamate semialdehyde and glutamate. This reaction is a part of the urea cycle and the glutamate and proline metabolism pathways, which are essential for the detoxification of ammonia in the body and the production of urea, proline, and glutamate, respectively.

Function

Ornithine aminotransferase is primarily found in the mitochondria of liver cells. Its main function is to facilitate the conversion of ornithine, a non-proteinogenic amino acid, into glutamate semialdehyde, which is then converted into glutamate, a key neurotransmitter and metabolic intermediate. This process is vital for the regulation of nitrogen levels in the body and plays a significant role in the urea cycle, a critical detoxification pathway that converts harmful ammonia into urea for excretion.

Genetic and Molecular Basis

The gene responsible for encoding ornithine aminotransferase is located on chromosome 10q26.13 and is known as the OAT gene. Mutations in the OAT gene can lead to a rare metabolic disorder known as Gyrate atrophy of the choroid and retina, characterized by progressive vision loss. This condition is inherited in an autosomal recessive manner and is due to the accumulation of ornithine in the blood and tissues, which is toxic to the retina.

Clinical Significance

Ornithine aminotransferase deficiency, resulting from mutations in the OAT gene, can cause gyrate atrophy of the choroid and retina. Patients with this condition often present with symptoms in late childhood or adolescence, including night blindness and progressive loss of peripheral vision. Diagnosis is typically made through genetic testing and measurement of ornithine levels in the blood and urine. Treatment may involve a low-protein diet and supplementation with vitamin B6 (pyridoxine), which can serve as a cofactor for OAT and potentially reduce ornithine levels.

Biochemical Assays and Research

Biochemical assays for ornithine aminotransferase activity involve measuring the conversion of ornithine and alpha-ketoglutarate to glutamate semialdehyde and glutamate. Research into OAT has focused on understanding its structure, function, and the impact of genetic mutations on its activity. This research has implications for the development of treatments for gyrate atrophy and other conditions associated with ornithine metabolism.

See Also

• Urea cycle
• Amino acid metabolism
• Metabolic disorder
• Genetic disorder