Glutamate-cysteine ligase modifier subunit (GCLM)

Glutamate-cysteine ligase modifier subunit (GCLM) is a regulatory protein that forms the heterodimeric glutamate-cysteine ligase (GCL) holoenzyme with the catalytic subunit (GCLC). GCL catalyzes the rate-limiting first step in the synthesis of glutathione, the major intracellular antioxidant. GCLM has no catalytic activity alone but enhances GCLC's efficiency, modifies substrate affinity, and decreases sensitivity to feedback inhibition. Dysregulated GCLM expression and function can impact cellular glutathione levels, influencing susceptibility to numerous diseases—such as cancer, neurodegeneration, and metabolic disorders—and influencing responses to oxidative stress and drugs.

Other names

Glutamate-Cysteine Ligase Regulatory ProteinGlutamate--Cysteine Ligase Modifier SubunitGlutamate-Cysteine Ligase, Modifier SubunitGamma-glutamylcysteine synthetase regulatory subunitGamma-Glutamylcysteine SynthetaseGCS light chainGLCLRGamma-ECS regulatory subunit

Inhibition of glutathione synthesis (through allosteric modulation or inhibition of the holoenzyme, affecting cellular oxidative stress response) and augmentation of GCLC enzyme activity (as a subunit, modulates kinetics and feedback inhibition properties).