Lanosterol biosynthesis

Lanosterol biosynthesis Cholesterol biosynthesis begins with the transformation of cytosolic acetyl CoA into lanosterol in a sequence of 15 reactions (Mitsche et al. 2015). The third of these, the reduction of beta-hydroxymethylglutaryl-coenzyme A (bHMG-CoA) to mevalonate (MVA) by bHMG-CoA reductase (HMGCR) is the tightly-regulated, rate-limiting step of cholesterol biosynthesis. It is also the target of the statin class of drugs.Cholesterol biosynthesis is altered in mice harboring mutations that block peroxisome assembly, suggesting that some steps of lanosterol synthesis might occur in peroxisomes (Faust & Kovacs 2014). These effects could be indirect, however, mediated by cellular ER stress responses to the peroxisome deficiency, consistent with the observation that absence of functional peroxisomes does not lead to deficiency of enzymes involved in cholesterol biosynthesis either in mutant mice or in peroxisome-deficient humans (Hogenboom et al. 2002). All the steps of this pathway have therefore been localized to the cytosol, mediated by cytosolic or ER membrane-associated enzymes.Statins are a class of medications that lower cholesterol levels in the blood. They work by inhibiting an enzyme called hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, which is involved in the production of cholesterol in the liver.