Mevalonate pathway enzymes (MVA pathway enzymes)

The mevalonate pathway is a fundamental metabolic sequence responsible for the synthesis of isoprenoids, including cholesterol, dolichol, and ubiquinone (Coenzyme Q10) (Mullen et al., 2016, Nature Reviews Cancer). It begins with the conversion of acetyl-CoA into mevalonate, a rate-limiting step catalyzed by 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) (StatPearls, Physiology, Cholesterol). This pathway is a major therapeutic target; statins competitively inhibit HMGCR to lower LDL cholesterol and reduce cardiovascular disease risk (Grundy, 1988, New England Journal of Medicine). Additionally, the pathway produces intermediates like farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), which are essential for the post-translational prenylation of proteins such as Ras and Rho, influencing cell growth and survival (Wang and Casey, 2016, Nature Reviews Cancer). Nitrogen-containing bisphosphonates target farnesyl pyrophosphate synthase (FPPS) within this pathway to treat bone-resorptive disorders like osteoporosis (Russell, 2011, Osteoporosis International). Dysregulation of mevalonate pathway enzymes is implicated in various pathologies, including cancer, where increased flux supports rapid cell proliferation, and rare genetic disorders like mevalonate kinase deficiency (Haas and Hoffmann, 2006, Orphanet Journal of Rare Diseases).

Other names

Isoprenoid pathwayHMG-CoA reductase pathwayMevalonate cascadeMVA pathway

Competitive inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) to block mevalonate production; inhibition of farnesyl pyrophosphate synthase (FPPS) to prevent the formation of isoprenoid intermediates required for protein prenylation.