Reaction: glycine + tetrahydrofolate + NAD+ = 5,10-methylenetetrahydrofolate + NH3 + CO2 + NADH
Other name(s): GCV
Systematic name: glycine:NAD+ 2-oxidoreductase (tetrahydrofolate-methylene-adding)
Comments: 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 α-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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Motokawa, Y. and Kikuchi, G. Glycine metabolism by rat liver mitochondria. Reconstruction of the reversible glycine cleavage system with partially purified protein components. Arch. Biochem. Biophys. 164 (1974) 624-633. [PMID: 4460882]
2. Hiraga, K. and Kikuchi, G. The mitochondrial glycine cleavage system. Functional association of glycine decarboxylase and aminomethyl carrier protein. J. Biol. Chem. 255 (1980) 11671-11676. [PMID: 7440563]
3. Okamura-Ikeda, K., Fujiwara, K. and Motokawa, Y. Purification and characterization of chicken liver T-protein, a component of the glycine cleavage system. J. Biol. Chem. 257 (1982) 135-139. [PMID: 7053363]
4. Fujiwara, K., Okamura-Ikeda, K. and Motokawa, Y. Mechanism of the glycine cleavage reaction. Further characterization of the intermediate attached to H-protein and of the reaction catalyzed by T-protein. J. Biol. Chem. 259 (1984) 10664-10668. [PMID: 6469978]
5. Okamura-Ikeda, K., Ohmura, Y., Fujiwara, K. and Motokawa, Y. Cloning and nucleotide sequence of the gcv operon encoding the Escherichia coli glycine-cleavage system. Eur. J. Biochem. 216 (1993) 539-548. [PMID: 8375392]