5-oxoprolinase (ATP-hydrolysing) (OPLAH)

5-oxoprolinase (ATP-hydrolysing), commonly abbreviated as OPLAH, is an enzyme that acts as a homodimer and uses ATP hydrolysis to catalyze the conversion of 5-oxo-L-proline to L-glutamate, a crucial step in the gamma-glutamyl cycle and essential for glutathione biosynthesis. This enzyme is a member of the hydrolase family, specifically those acting on carbon-nitrogen bonds in cyclic amides. Genetic defects in OPLAH lead to 5-oxoprolinase deficiency (OPLAHD), an inborn error of metabolism characterized by elevated 5-oxoproline and can result in metabolic acidosis. OPLAH plays an important role in intracellular cysteine delivery and protection against cysteine toxicity by maintaining glutathione homeostasis. While it has significant biochemical and disease associations, no approved drugs directly target OPLAH, but its function can be modulated through substrate analogs that increase glutathione synthesis.

Other names

5-OPase5-oxo-L-prolinaseOPLAOPLAHD5-OPASEPyroglutamaseoxoprolinasepyroglutamate hydrolasepyroglutamic hydrolaseL-pyroglutamate hydrolase

Substrate analogs such as L-2-oxothiazolidine-4-carboxylate are metabolized by 5-oxoprolinase to enhance glutathione production