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

3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) is the rate-limiting enzyme in the mevalonate pathway, which is the metabolic route for the endogenous synthesis of cholesterol and other isoprenoids (UniProt: P04035). Located primarily in the endoplasmic reticulum of hepatocytes, it catalyzes the conversion of HMG-CoA to mevalonate using NADPH as a reducing agent (PubMed: 11574408). Dysregulation or high activity of this enzyme leads to elevated levels of low-density lipoprotein cholesterol (LDL-C), a major risk factor for atherosclerosis and coronary heart disease (StatPearls: NBK430910). Rosuvastatin and other statins function as competitive inhibitors of HMG-CoA reductase, binding to the active site with higher affinity than the natural substrate (PubChem: CID 126457). This inhibition reduces intracellular cholesterol levels, prompting the liver to up-regulate LDL receptors, which enhances the clearance of LDL-C from the systemic circulation (NIH: LiverTox).

Other names

HMGCR3-hydroxy-3-methylglutaryl-CoA reductaseHMG-CoA reductase

Competitive inhibition of the HMG-CoA reductase enzyme, which catalyzes the rate-limiting step in cholesterol synthesis.