6-phosphogluconolactonase (PGLS)

6-phosphogluconolactonase (PGLS) is a cytosolic enzyme that catalyzes the hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate in the oxidative branch of the pentose phosphate pathway[2]. This reaction is critical for the generation of NADPH, which supports reductive biosynthesis and maintains redox balance in cells. PGLS activity regulates key intermediate concentrations in the pentose phosphate pathway and prevents accumulation of byproducts that may disrupt cellular metabolism[1]. Disruption of PGLS activity leads to reduced NADPH production, increased oxidative stress, altered energy metabolism, and decreased cell viability[1]. As part of the pentose phosphate pathway, PGLS is essential for cell proliferation and response to oxidative stress, and its activity is particularly relevant in diseases displaying altered metabolism such as cancer[1][2]. No approved drugs directly target human PGLS, but similar enzymes are being explored as antiparasitic targets in trypanosomal infections[2].

Other names

6PGLPGLSHEL-S-304epididymis secretory protein Li 304epididymis secretory sperm binding protein

Inhibition of PGLS would block hydrolysis of 6-phosphogluconolactone, disrupting NADPH production and impairing cellular redox balance[2]