Glutamate--cysteine ligase catalytic subunit

Glutamate–cysteine ligase catalytic subunit (GCLC) is the catalytic component of the rate-limiting enzyme in glutathione biosynthesis, catalyzing ATP-dependent ligation of L-glutamate and L-cysteine (UniProt: P48506). Glutathione is a critical intracellular antioxidant and redox regulator essential for cellular defense against oxidative stress.

GCLC is implicated in congenital non-spherocytic hemolytic anemia type 7, an autosomal recessive disorder characterized by glutathione deficiency, myopathy, and neurodegeneration including spinocerebellar degeneration and peripheral neuropathy (UniProt: P48506). The enzyme's role in glutathione homeostasis links it to cellular oxidative stress management across multiple tissues.

In Alzheimer's disease, GCLC shows ambiguous regulation across subcellular fractions in post-mortem AD brain compared to age-matched controls by TMT-labeled quantitative proteomics (Chaparral AD proteomics). The mean log2 fold-change is 0.1282 across two fractions, suggesting subtle or differential changes in distribution rather than consistent up- or down-regulation, indicating potential dysregulation of antioxidant capacity in AD-affected brain tissue.