EC - Glycine cleavage system

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IntEnz Enzyme Nomenclature


Accepted name:
glycine cleavage system
Other name:
Systematic name:
glycine:NAD+ 2-oxidoreductase (tetrahydrofolate-methylene-adding)



The glycine cleavage (GCV) system is a large multienzyme complex that belongs to the 2-oxoacid dehydrogenase complex family, which also includes EC, branched-chain α-keto acid dehydrogenase system, EC, 2-oxoglutarate dehydrogenase system, EC, pyruvate dehydrogenase system, and EC, 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, glycine dehydrogenase (aminomethyl-transferring)), T protein (EC, aminomethyltransferase), L protein (EC, 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

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB


  1. Motokawa, Y., Kikuchi, G.
    Glycine metabolism by rat liver mitochondria. Reconstruction of the reversible glycine cleavage system with partially purified protein components.
    Arch. Biochem. Biophys. 164 : 624-633 (1974). [PMID: 4460882]
  2. Hiraga, K., Kikuchi, G.
    The mitochondrial glycine cleavage system. Functional association of glycine decarboxylase and aminomethyl carrier protein.
    J. Biol. Chem. 255 : 11671-11676 (1980). [PMID: 7440563]
  3. Okamura-Ikeda, K., Fujiwara, K., Motokawa, Y.
    Purification and characterization of chicken liver T-protein, a component of the glycine cleavage system.
    J. Biol. Chem. 257 : 135-139 (1982). [PMID: 7053363]
  4. Fujiwara, K., Okamura-Ikeda, K., 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 : 10664-10668 (1984). [PMID: 6469978]
  5. Okamura-Ikeda, K., Ohmura, Y., Fujiwara, K., Motokawa, Y.
    Cloning and nucleotide sequence of the gcv operon encoding the Escherichia coli glycine-cleavage system.
    Eur. J. Biochem. 216 : 539-548 (1993). [PMID: 8375392]

[EC created 2020]