3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (HMGCR)

3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is the rate-limiting enzyme in the mevalonate pathway, which is the metabolic route for the endogenous synthesis of cholesterol and other essential isoprenoids [2, 4, 10]. Primarily located in the endoplasmic reticulum of hepatocytes, HMGCR catalyzes the conversion of HMG-CoA to mevalonate using NADPH as a cofactor [5, 10]. Dysregulation of this enzyme or excessive cholesterol production is a central factor in the development of hypercholesterolemia, which significantly increases the risk of atherosclerotic cardiovascular disease [4, 12]. HMGCR is the primary therapeutic target for statins, a class of competitive inhibitors that reduce hepatic cholesterol synthesis [2, 16]. This reduction triggers a compensatory upregulation of low-density lipoprotein (LDL) receptors on the surface of liver cells, leading to increased clearance of LDL cholesterol from the circulation [4, 10, 12]. Beyond its lipid-lowering effects, HMGCR inhibition is thought to exert pleiotropic benefits, including improved endothelial function and reduced systemic inflammation [7, 12, 16].

Other names

HMG-CoA reductase3-hydroxy-3-methylglutaryl-CoA reductaseHydroxymethylglutaryl-CoA reductaseHMDHLDLCQ3

Competitive inhibition of HMG-CoA reductase, preventing the conversion of HMG-CoA to mevalonate, which leads to decreased hepatic cholesterol synthesis and subsequent upregulation of LDL receptors to increase clearance of LDL from the blood [4, 10, 12].