Glycerol-3-phosphate dehydrogenase 2 (GPD2)

Glycerol-3-phosphate dehydrogenase 2 (GPD2) is a mitochondrial enzyme that catalyzes the oxidation of glycerol-3-phosphate to dihydroxyacetone phosphate, transferring electrons from FAD to ubiquinone in the electron transport chain. This reaction forms a critical part of the glycerol phosphate shuttle, connecting glycolysis and oxidative phosphorylation, regulating NAD+/NADH balance, and contributing to lipid biosynthesis. GPD2 is structurally conserved and shares homology with bacterial GlpD, which has been extensively characterized. GPD2 plays essential roles in cellular metabolism, is regulated under various stress conditions, and alterations in its activity are associated with cancer, obesity, and diabetes. It is a candidate metabolic target but not the subject of approved direct drugs at present.

Other names

mitchondrial glycerol-3-phosphate dehydrogenaseGPD2GlpD (ortholog in bacteria)alphaGPDHGPDH (less specific; encompasses the family)

Inhibitors would block electron transfer from glycerol-3-phosphate, impairing NADH/FADH2 reoxidation and mitochondrial function. Targeting GPD2 could disrupt the glycerol phosphate shuttle, affecting glycolysis and lipid biosynthesis.