title: Mevalonate Cascade and its Regulation in Cholesterol Metabolism in Different Tissues in Health and Disease.
abstract: The cholesterol biosynthesis pathway, also referred to as the mevalonate (MVA) pathway, is responsible for the biosynthesis of two key isoprenoids: farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Post-translational modification of small GTPases by FPP and GGPP has captured much attention due to their potential contribution to cancer, cardiovascular and neurodegenerative diseases. The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) catalyzes the conversion of HMG-CoA to MVA, and is the rate-limiting step in the biosynthesis of cholesterol. Statins are HMGCR inhibitors that are used extensively in the treatment of hypercholesterolemia. Inhibitors of the MVA pathway exhibit anti-tumor effects and may reduce cancer incidence and cancer-related mortality in humans. In this review, we will focus on the mevalonate cascade and its regulation in cholesterol metabolism as well as polymorphisms of the MVA cascade in cancer development, infectious and cardiovascular disease (CVD).
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hashemi
authors.forename: Reyhane
authors.initials: R
authors.lastname: Hoshyar
authors.forename: Sudharsana R
authors.initials: SR
authors.lastname: Ande
authors.forename: Qi M
authors.initials: QM
authors.lastname: Chen
authors.forename: Claudia
authors.initials: C
authors.lastname: Solomon
authors.forename: Anne
authors.initials: A
authors.lastname: Zuse
authors.forename: Mohammad
authors.initials: M
authors.lastname: Naderi
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D007239:Infections / Q000378:metabolism*; D008798:Mevalonic Acid / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D012717:Sesquiterpenes / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000214:Acyl Coenzyme A; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; C004808:farnesyl pyrophosphate; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D020558:GTP Phosphohydrolases; C002963:geranylgeranyl pyrophosphate; D008798:Mevalonic Acid
keywords: 3-hydroxy-3-
  methylglutaryl-coenzyme A.; Farnesyl pyrophosphate; Rho GTPase; geranylgeranyl pyrophosphate; mevalonate cascade; statin