Mevalonate Cascade and its Regulation in Cholesterol Metabolism in Different Tissues in Health and Disease

Author(s): Mohammad Hashemi, Reyhane Hoshyar, Sudharsana R. Ande, Qi M. Chen, Claudia Solomon, Anne Zuse, Mohammad Naderi.

Journal Name: Current Molecular Pharmacology

Volume 10 , Issue 1 , 2017

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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).

Keywords: Farnesyl pyrophosphate, geranylgeranyl pyrophosphate, mevalonate cascade, Rho GTPase, statin, 3-hydroxy-3- methylglutaryl-coenzyme A.

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Article Details

VOLUME: 10
ISSUE: 1
Year: 2017
Page: [13 - 26]
Pages: 14
DOI: 10.2174/1874467209666160112123746
Price: $65

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