GCV2 encodes a glycine decarboxylase known as the P subunit of the glycine cleavage system or glycine decarboxylase complex (GDC). GDC is a multienzyme complex that catalyzes the reversible oxidative cleavage of glycine into CO2 and NH3 and connects the metabolism of one, two and three-carbon compounds as shown in this pathway diagram. The other subunits of the GDC complex are: Gcv1p (the T-protein), a tetrahydrofolate transferase, Gcv3p (the H-protein), a carrier protein containing lipoamide, and Lpd1p (the L-protein), a lipoamide dehydrogenase. Gcv1p, Gcv2p and Gcv3p are unique to the GDC complex but Lpd1p acts in several other complexes including pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase, and a branched chain oxo-acid dehydrogenase (4, 5, 1). GCV1, GCV2 and GCV3 are collectively referred to as the GCV genes and are up-regulated by glycine and one-carbon unit levels (5,10-CH2-H4folate).

GCV2 expression is induced by glycine and methionine and repressed in rich medium or by nitrogen sources (1, 6). GCV2 transcription is regulated, in different nutritional conditions, by three proteins: a Glycine Regulatory Region (GRR)-binding protein that binds to an 11bp sequence (TGACTCTTCTT), a GATA-binding protein of the nitrogen catabolite repression (NCR) set of transcription factors and a protein that binds a palindrome sequence (AAGGaCCTT) (7). Although the GRR region contains a consensus binding site for Bas1p transcription factor, conflicting reports have been published on the role of Bas1p in regulating GCV2 expression in response to glycine (8, 3, 9). While mutation of the Bas1p binding site doesn't affect glycine response (8), loss of Bas1p reduces the repression of GCV2 in response to glycine withdrawal (9).

Gcv2p is highly conserved from bacteria to humans (1). Mutations in the human glycine decarboxylase gene (GLDC) result in Glycine encephalopathy or Nonketotic hyperglycinemia (NKH) (10).

Last updated: 2007-12-11