GLDC

GLDC is the gene symbol for glycine decarboxylase, the P-protein component of the mitochondrial glycine cleavage system. This enzyme participates in the breakdown of glycine and contributes to one-carbon metabolism by feeding one-carbon units into folate-mediated reactions.

In the glycine cleavage system, the P-protein, the H-protein, and the T-protein work in concert to decarboxylate glycine and transfer the resulting methylene group to tetrahydrofolate, forming 5,10-methylene-tetrahydrofolate. The GLDC-encoded P-protein is typically pyridoxal phosphate–dependent and operates within the mitochondrial matrix, with the H- and T-proteins facilitating subsequent steps and recycling of cofactors.

Genetics and clinical significance: Mutations in GLDC are among the common genetic causes of nonketotic glycine encephalopathy (glycine encephalopathy), an autosomal recessive disorder. Affected individuals may have elevated glycine levels in plasma and cerebrospinal fluid, and clinical presentations range from severe neonatal encephalopathy to later-onset developmental delay, hypotonia, and seizures. Diagnosis is based on biochemical profiling and confirmation by molecular genetic testing of the GLDC gene.

Additional notes: GLDC variants can have a range of effects on enzyme activity, and genotype-phenotype correlations are an active area of research. GLDC is one component of the glycine cleavage system, and its proper function is connected to broader cellular one-carbon metabolism.

See also: glycine cleavage system; GCSH; AMT; DLD; glycine encephalopathy.