6-phosphogluconate dehydrogenase (6PGDH)

6-phosphogluconate dehydrogenase Overview

6-phosphogluconate dehydrogenase (6PGDH) is an enzyme that catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose-5-phosphate and CO₂, with concomitant reduction of NADP⁺ to NADPH. It is the third step in the oxidative branch of the pentose phosphate pathway (PPP), which is crucial for generating NADPH for reductive biosynthesis and antioxidant defense, and for producing ribulose-5-phosphate for nucleotide synthesis. 6PGDH is a homodimer expressed in most tissues, particularly those with high biosynthetic or antioxidant demands. Mutations can cause 6-phosphogluconate dehydrogenase deficiency, leading to hemolytic anemia. It also regulates metabolism in regulatory T cells (Tregs), implicating it as a metabolic checkpoint relevant to immunotherapy applications.

Mechanism of Action

Inhibition of 6-phosphogluconate dehydrogenase leads to reduced Treg suppressive function and shifts toward pro-inflammatory phenotypes.

Biological Functions

Safety Considerations