Glycerol-3-phosphate dehydrogenase, mitochondrial (GPD2) (mGPDH)

Glycerol-3-phosphate dehydrogenase, mitochondrial (GPD2 or mGPDH) is a flavin-linked enzyme located on the outer surface of the inner mitochondrial membrane. It serves as a rate-limiting component of the glycerol-3-phosphate shuttle, which is essential for transferring reducing equivalents from cytosolic NADH to the mitochondrial electron transport chain, thereby maintaining the redox balance necessary for continued glycolysis. This enzyme acts at the intersection of carbohydrate and lipid metabolism, converting glycerol-3-phosphate into dihydroxyacetone phosphate to support hepatic gluconeogenesis and energy production. In therapeutic contexts, mGPDH has been identified as a major target for the antidiabetic drug metformin, which is thought to inhibit the enzyme to reduce hepatic glucose output, although this mechanism is currently a topic of scientific debate. Additionally, mGPDH is overexpressed in various cancers, such as prostate and thyroid cancer, where it supports the heightened metabolic requirements and oxidative stress management of tumor cells.

Other names

Mitochondrial glycerol-3-phosphate dehydrogenaseGPD2FAD-linked glycerol-3-phosphate dehydrogenaseAlpha-glycerophosphate dehydrogenasesn-Glycerol-3-phosphate dehydrogenase 2

Non-competitive inhibition of mGPDH activity to alter the cytosolic redox state and suppress hepatic gluconeogenesis.