Glycine dehydrogenase (decarboxylating)

Glycine dehydrogenase (decarboxylating), often abbreviated as GLDC, is an enzyme that catalyzes the oxidative decarboxylation of glycine. It is a component of the glycine cleavage system (GCS), also known as glycine decarboxylase complex, which is a mitochondrial multienzyme complex responsible for the degradation of glycine.

The systematic name for this enzyme is glycine:tetrahydrofolate oxidoreductase (decarboxylating). It plays a crucial role in one-carbon metabolism and the interconversion of glycine and serine.

The reaction catalyzed by glycine dehydrogenase (decarboxylating) is:

Glycine + Tetrahydrofolate + NAD+ <-> 5,10-Methylenetetrahydrofolate + NH3 + CO2

The enzyme requires pyridoxal phosphate (PLP) as a cofactor. The glycine cleavage system, in which GLDC operates, involves several other enzymes: aminomethyltransferase (AMT), dihydrolipoyl dehydrogenase (DLD), and tetrahydrofolate synthase (THFS). Together, these enzymes contribute to the complete oxidation of glycine.

Deficiencies in glycine dehydrogenase (decarboxylating) can lead to nonketotic hyperglycinemia (NKH), a severe metabolic disorder characterized by the accumulation of glycine in body fluids, particularly in the brain. This can result in neurological problems such as seizures, developmental delay, and intellectual disability. Diagnosis of NKH typically involves measuring glycine levels in plasma and cerebrospinal fluid. Genetic testing can confirm mutations in the GLDC gene, which encodes glycine dehydrogenase (decarboxylating).