3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)

3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the rate-limiting enzyme in the mevalonate pathway, which is essential for the endogenous production of cholesterol and other isoprenoids (UniProt P04035). Located in the endoplasmic reticulum membrane, HMGCR catalyzes the four-electron reduction of HMG-CoA to mevalonate using NADPH. This enzyme is the primary target for statins, the most widely prescribed class of drugs for treating hypercholesterolemia and preventing cardiovascular disease (PubMed: 25282161). Recent research has identified bioactive food-derived peptides, such as Lupin peptide P5 (sequence: LILPKHSDAD), which act as natural inhibitors of HMGCR (PubMed: 24512315). These peptides mimic the action of statins by binding to the enzyme's catalytic site, thereby reducing cholesterol synthesis and promoting the expression of LDL receptors to enhance clearance of circulating cholesterol (PubMed: 28603069). The study of P5 highlights the potential of lupin-derived components as functional foods or nutraceuticals for managing lipid levels.

Other names

HMG-CoA reductase3-hydroxy-3-methyl-glutaryl-CoA reductaseHMGCR

Competitive inhibition of the enzyme 3-hydroxy-3-methylglutaryl-CoA reductase, which prevents the conversion of HMG-CoA to mevalonate, the rate-limiting step in cholesterol biosynthesis.