From the Guidelines
Mevalonic acid is a crucial intermediate in the cholesterol synthesis pathway, and its production is targeted by statin medications to lower cholesterol levels in patients with hypercholesterolemia. Mevalonic acid is formed when the enzyme HMG-CoA reductase converts 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, a critical step in the mevalonate pathway 1. This pathway is essential for the synthesis of cholesterol, steroid hormones, bile acids, vitamin D, and various other biologically important molecules.
Some of the key points about mevalonic acid include:
- It is a key intermediate compound in the metabolic pathway that produces cholesterol and other isoprenoids in the human body
- Its production is the target of statin medications, which inhibit HMG-CoA reductase to lower cholesterol levels in patients with hypercholesterolemia
- Beyond its role in cholesterol synthesis, mevalonic acid is also important for cell growth and protein prenylation, which affects cell signaling and protein function
- Defects in mevalonic acid metabolism can lead to rare genetic disorders like mevalonic aciduria, characterized by developmental delays, recurrent fevers, and other symptoms
Understanding mevalonic acid's role helps explain how statins work and why they have both therapeutic effects and potential side effects related to blocking this important metabolic pathway, as discussed in the context of very low LDL-C levels and their potential effects on cardiovascular events 1.
From the Research
Definition of Mevalonic Acid
- Mevalonic acid is a key intermediate in the biosynthesis of cholesterol, also known as the mevalonate (MVA) pathway 2, 3, 4, 5, 6
- It is produced through the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) by the enzyme HMG-CoA reductase, which is the rate-limiting step in cholesterol biosynthesis 2, 4, 5, 6
Role of Mevalonic Acid in Cell Metabolism
- Mevalonic acid is essential for the synthesis of isoprenoids, including sterols and non-sterol isoprenoids, which are necessary for diverse biological functions 3, 4, 5
- Cholesterol, a major product of the mevalonate pathway, plays a crucial role in maintaining cell membrane structure and function, as well as regulating cell cycle progression 3, 4
- Mevalonic acid-derived metabolites, such as dolichols, ubiquinone side chains, and isopentenyladenosine derivatives, may also be involved in cell proliferation and survival 4
Relationship between Mevalonic Acid and Cancer
- Inhibition of the mevalonate pathway by statins, which are HMG-CoA reductase inhibitors, has been shown to exhibit anti-tumor effects and may reduce cancer incidence and mortality 2, 5
- The balance between induction and inhibition of the mevalonate pathway may regulate cancer suppression by statins, with lipophilic statins having different effects on extra-hepatic cells compared to hydrophilic statins 5