Aminomethyltransferase

Aminomethyltransferase, also known as the glycine cleavage system T-protein, is a mitochondrial enzyme that participates in the glycine cleavage system (GCS). It catalyzes the transfer of the aminomethyl group from the lipoylated H-protein to tetrahydrofolate, producing methylene-tetrahydrofolate as part of the cellular one-carbon metabolism. This reaction links glycine catabolism to the folate cycle and supports the generation of one-carbon units used in various biosynthetic processes.

The glycine cleavage system comprises four components: P-protein (glycine decarboxylase), H-protein (lipoamide-containing carrier), T-protein (aminomethyltransferase), and L-protein (dihydrolipoamide dehydrogenase). The T-protein accepts the aminomethyl moiety from the H-protein and transfers it to tetrahydrofolate, thereby regenerating the lipoamide on the H-protein. The system is localized mainly in mitochondria in animals and in chloroplasts/mitochondria in plants, functioning in concert with the P- and L-proteins.

In humans, the enzyme is encoded by the AMT gene. Mutations in AMT or other GCS components can cause nonketotic hyperglycinemia, a neurometabolic disorder characterized by elevated glycine levels in plasma and cerebrospinal fluid and by seizures, hypotonia, and developmental delays. The glycine cleavage system is also found in many bacteria and plants, where it participates in amino acid catabolism and one-carbon metabolism.