The glycine cleavage (GCV) system is a large multienzyme complex that belongs to the 2-oxoacid dehydrogenase complex family, which also includes EC
1.2.1.25, branched-chain alpha-keto acid dehydrogenase system, EC
1.2.1.105, 2-oxoglutarate dehydrogenase system, EC
1.2.1.104, pyruvate dehydrogenase system, and EC
2.3.1.190, acetoin dehydrogenase system. The GCV system catalyses the reversible oxidation of glycine, yielding carbon dioxide, ammonia, 5,10-methylenetetrahydrofolate and a reduced pyridine nucleotide. Tetrahydrofolate serves as a recipient for one-carbon units generated during glycine cleavage to form the methylene group. The GCV system consists of four protein components, the P protein (EC
1.4.4.2, glycine dehydrogenase (aminomethyl-transferring)), T protein (EC
2.1.2.10, aminomethyltransferase), L protein (EC
1.8.1.4, dihydrolipoyl dehydrogenase), and the non-enzyme H protein (lipoyl-carrier protein). The P protein catalyses the pyridoxal phosphate-dependent liberation of CO2 from glycine, leaving a methylamine moiety. The methylamine moiety is transferred to the lipoic acid group of the H protein, which is bound to the P protein prior to decarboxylation of glycine. The T protein catalyses the release of ammonia from the methylamine group and transfers the remaining C1 unit to tetrahydrofolate, forming 5,10-methylenetetrahydrofolate. The L protein then oxidizes the lipoic acid component of the H protein and transfers the electrons to NAD+, forming NADH.
