Glycerol-3-phosphate dehydrogenase (GPDH)

Glycerol-3-phosphate dehydrogenase (GPDH) is an enzyme that catalyzes the reversible redox conversion of dihydroxyacetone phosphate (DHAP) to glycerol-3-phosphate (G3P). This reaction is central to carbohydrate and lipid metabolism, including respiration, glycolysis, and phospholipid biosynthesis. There are two main forms: cytosolic GPDH (GPD1), an NAD+-dependent enzyme, and mitochondrial GPDH (GPD2), which uses quinol/quinone. GPDH functions as a dimer with two protein domains: an N-terminal NAD-binding domain and a C-terminal substrate-binding and catalytic domain. Key active site residues include Lys120, Asp260, Arg269, and Asn270. The enzyme undergoes conformational changes upon substrate binding, utilizing a hydride transfer mechanism where Lys120 donates a proton to the carbonyl of DHAP. GPDH is highly conserved across virtually all organisms and plays a critical role in the glycerol phosphate shuttle, connecting glycolysis to lipid metabolism and maintaining cellular redox balance. Its role in glycerol metabolism and connection to insulin signaling and obesity suggests potential relevance to metabolic disorders.

Other names

Cytosolic GPDHGPD1Mitochondrial GPDHGPD2