Mitochondrial 2-ketoacid dehydrogenase complex and glycine cleavage system

The mitochondrial 2-ketoacid dehydrogenase complexes and glycine cleavage system refer to two distinct, though sometimes functionally interconnected, multienzyme complexes located in the mitochondrial matrix. The glycine cleavage system (GCS) is composed of four proteins (P-, H-, T-, and L-protein) that catalyze the reversible degradation of glycine into CO₂, NH₃, and a methylene group transferred to tetrahydrofolate, central to one-carbon and energy metabolism[1][3][5]. The H-protein acts as a mobile shuttle among the other proteins[2]. Dysfunctional GCS activity is strongly linked to inborn errors such as nonketotic hyperglycinemia, characterized by elevated glycine in body fluids and severe neurological symptoms[5]. The GCS shares components and lipoic acid modification systems with other mitochondrial multienzyme complexes such as the pyruvate dehydrogenase complex, collectively known as the 2-oxoacid dehydrogenase complexes, which catalyze key irreversible steps in central metabolism[1]. Both complex groups are fundamentally important for mitochondrial function and cellular energy homeostasis.

Other names

2-oxoacid dehydrogenase complexesglycine decarboxylase complexglycine cleavage system (GCS)glycine synthase (reverse direction)glycine dehydrogenase (for component P-protein)aminomethyltransferase (for component T-protein)dihydrolipoamide dehydrogenase (for component L-protein)H-protein (for component H-protein)

Enzymatic cleavage or synthesis of glycine Modulators of glycine metabolism may act by diverting glycine to alternative metabolic routes (as with sodium benzoate in management)