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
Keywords: Farnesyl pyrophosphate, geranylgeranyl pyrophosphate, mevalonate cascade, Rho GTPase, statin, 3-hydroxy-3-
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