Glycerol-metabolizing enzymes

Glycerol-metabolizing enzymes are a functional group of proteins that regulate the flux of glycerol through key metabolic pathways, including glycolysis, gluconeogenesis, and lipid biosynthesis [1, 11]. This group primarily includes glycerol kinase (GK), which initiates glycerol utilization by phosphorylating it to glycerol-3-phosphate (G3P), and glycerol-3-phosphate dehydrogenase (GPDH), which facilitates the entry of G3P into the mitochondrial electron transport chain via the glycerol phosphate shuttle [7, 15]. These enzymes are essential for maintaining systemic energy homeostasis, cellular redox balance, and the synthesis of triacylglycerols and phospholipids [8, 18]. Dysregulation of these enzymes is implicated in the pathogenesis of metabolic disorders such as type 2 diabetes, obesity, and nonalcoholic fatty liver disease (NAFLD), as well as in the metabolic reprogramming of cancer cells and neurodegenerative conditions like Parkinson's disease [2, 17, 22]. Therapeutic targeting of these enzymes is an active area of research; for example, the antidiabetic drug metformin has been identified as an inhibitor of mitochondrial GPDH, while various small molecules like FSG67 and iGP-1 are being developed to target glycerol-3-phosphate acyltransferase (GPAT) and GPDH, respectively [12, 23]. Despite their therapeutic potential, targeting these enzymes poses challenges such as maintaining glucose stability and avoiding disruptions to essential lipid signaling pathways [6, 20].

Other names

Enzymes of glycerol metabolismGlycerol metabolic enzymes

Inhibition of glycerol phosphorylation by glycerol kinase, inhibition of glycerol-3-phosphate oxidation by mitochondrial glycerol-3-phosphate dehydrogenase, and inhibition of triacylglycerol synthesis by glycerol-3-phosphate acyltransferase.