Mevalonate pathway

The Mevalonate pathway, also known as the Isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria.

The pathway produces two five-carbon building blocks called isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are used to make isoprenoids, a diverse class of over 30,000 biomolecules such as cholesterol, heme, vitamin K, coenzyme Q10, and all steroid hormones.

The mevalonate pathway begins with acetyl-CoA and ends with the production of IPP and DMAPP.

It is best known as the target of statins, a class of cholesterol lowering drugs. The drug Lipitor (Atorvastatin) inhibits HMG-CoA reductase within the mevalonate pathway. As of 2015, Lipitor remains the world's best selling drug of all time with $125 Billion USD in sales.


Lovastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that impacts the mevalonate pathway. The inhibition of intermediates in the mevalonate pathway affects signaling cascades and oncogenes associated with brain tumor stem cells (BTSC). In a review, Amadasu et al. showed the possible mechanisms where lovastatin can target BTSC for different varieties of malignant brain tumors 1).

1)
Amadasu E, Kang R, Usmani A, Borlongan CV. Effects of Lovastatin on Brain Cancer Cells. Cell Transplant. 2022 Jan-Dec;31:9636897221102903. doi: 10.1177/09636897221102903. PMID: 35670207.