HMG-CoA reductase (
3-hydroxy-3-methyl-glutaryl-CoA reductase, officially abbreviated
HMGCR) is the rate-controlling
enzyme (NADH-dependent, ; NADPH-dependent, ) of the
mevalonate pathway, the metabolic pathway that produces
cholesterol and other
isoprenoids. Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of
low density lipoprotein (LDL) via the LDL receptor as well as oxidized species of cholesterol. Competitive inhibitors of the reductase induce the expression of LDL receptors in the liver, which in turn increases the catabolism of plasma LDL and lowers the plasma concentration of cholesterol, an important determinant of atherosclerosis. This enzyme is thus the target of the widely available cholesterol-lowering drugs known collectively as the
statins.