Glucose-6-phosphate 1-dehydrogenase (G6PD) (G6PD)

Glucose-6-phosphate 1-dehydrogenase (G6PD) is a ubiquitous, cytosolic enzyme encoded by an X-linked gene (Xq28 in humans). It catalyzes the first, rate-limiting step of the oxidative pentose phosphate pathway, converting glucose-6-phosphate to 6-phosphoglucono-δ-lactone while producing NADPH. NADPH is essential for maintaining the cellular redox state, particularly in red blood cells, which lack alternative NADPH-producing pathways. The enzyme is structurally conserved across species, typically functioning as a dimer or tetramer, and contains specific binding sites for both substrate and coenzyme (NADP+). G6PD deficiency, caused by mutations in the G6PD gene, is one of the most common enzymopathies worldwide, leading to increased susceptibility to oxidative stress, neonatal jaundice, and acute hemolytic anemia. The enzyme is regulated by the NADP+/NADPH ratio, acetylation status, and transcription factors, reflecting its central role in cellular metabolism and defense against oxidative damage.

Other names

Glucose-6-phosphate dehydrogenaseG6PDHD-glucose-6-phosphate dehydrogenaseglucose-6-phosphate 1-dehydrogenase (EC 1.1.1.49)

G6PD catalyzes the conversion of glucose-6-phosphate to 6-phosphoglucono-δ-lactone, reducing NADP+ to NADPH. Its activity is stimulated by a high NADP+/NADPH ratio and negatively regulated by acetylation at Lys403, with SIRT2-dependent deacetylation restoring activity. Class I mutations destabilize the enzyme, leading to clinical deficiency. The enzyme is also stimulated by its substrate (G6P) and inhibited by its product (NADPH) in a regulatory loop.