3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR)

3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) is the key rate-limiting enzyme of the mevalonate pathway, catalyzing the conversion of HMG-CoA to mevalonate, an essential precursor in cholesterol and isoprenoid biosynthesis[1][3][7]. It is a polytopic endoplasmic reticulum membrane protein with a sterol-sensing domain and a C-terminal catalytic region[1]. HMGCR is tightly regulated by intracellular cholesterol levels and represents the principal target of statin drugs—widely used lipid-lowering agents for prevention and management of cardiovascular disease[1][3][4][6]. Inhibition of this enzyme reduces endogenous cholesterol synthesis and increases hepatic LDL receptor expression, thereby lowering circulating LDL cholesterol and overall CV risk[4][6]. Safety concerns for drugs targeting this enzyme include myopathy and hepatotoxicity[4][6]. Key corrections and conventions: The correct, accepted canonical name is “3-hydroxy-3-methyl-glutaryl-coenzyme A reductase.” The commonly used abbreviation is "HMGCR." It is an important enzyme (not a receptor, transporter, or transcription factor). Its main biological and therapeutic importance is as the molecular target of the statin class of lipid-lowering drugs[1][2][3][4][6][8].

Other names

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

Competitive inhibition of HMG-CoA reductase active site; Blockade of cholesterol biosynthesis; Upregulation of hepatic LDL receptor expression (secondary to intracellular cholesterol depletion)