Glycine dehydrogenase (decarboxylating), mitochondrial (GLDC)

Glycine dehydrogenase (decarboxylating), mitochondrial (GLDC), is a pyridoxal phosphate-dependent enzyme and a core component (P-protein) of the mitochondrial glycine cleavage system[1][2][4]. It catalyzes the first and rate-limiting step of glycine catabolism, binding glycine and facilitating its degradation with the release of CO₂, and transfer of the remaining methylamine group to the H-protein of the system[1][4]. This enzyme plays a critical role in amino acid metabolism, supplying one-carbon units to the folate pathway, which is essential for nucleotide synthesis and general cellular function[2][3]. Pathogenic variants in GLDC cause nonketotic hyperglycinemia (glycine encephalopathy), a severe metabolic brain disorder characterized by glycine accumulation and neurological deficits[2]. Recent research links GLDC to cancer biology, where its upregulation supports tumor growth, proliferation, and metabolism in several malignancies, including neuroblastoma and non-small cell lung cancer[3][5]. Mitochondrial, post-translational, and epigenetic regulation of GLDC are active areas of therapeutic interest. Key functions and disease links are well-documented; however, no drugs currently target GLDC specifically in approved clinical use. Its primary significance is as an essential enzyme of intermediary metabolism and as a pathogenic driver in inherited metabolic disease and cancer.

Other names

Glycine decarboxylaseGlycine cleavage system protein PGlycine decarboxylase P-proteinGlycine dehydrogenase (aminomethyl-transferring)Glycine dehydrogenase [decarboxylating], mitochondrialGlycine cleavage system P proteinGCSPGCEGCE1NKHHYGN1

Modulation of glycine cleavage system and glycine catabolism (for experimental therapies targeting glycine breakdown); Inhibition of GLDC activity (potential anti-cancer research area, often via indirect regulation, e.g., acetylation-mediated enzymatic suppression)[3]