Mevalonatederived

Mevalonate-derived refers to compounds produced from mevalonate or through the mevalonate pathway, a central route in isoprenoid biosynthesis found in animals, many fungi, plants, and some bacteria. In this pathway, acetyl-CoA units are assembled to form HMG-CoA, which is reduced to mevalonate. Mevalonate is then converted into the building blocks isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), the universal five-carbon units for isoprenoids.

From IPP and DMAPP, a variety of longer isoprenoids are synthesized, including farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). These intermediates serve as precursors for numerous mevalonate-derived products such as cholesterol, steroid hormones, and bile acids in animals; ubiquinone (coenzyme Q) and dolichols in membrane and electron transport processes; and a wide range of other terpenoids in plants and microorganisms. A notable function of many mevalonate-derived lipids is protein prenylation, wherein FPP or GGPP is covalently attached to target proteins (such as members of the Ras and Rho families) to promote membrane association and proper signaling.

Medical and research relevance includes the use of statins, which inhibit HMG-CoA reductase and reduce mevalonate production, thereby lowering downstream isoprenoids and cholesterol. Disruptions in the mevalonate pathway can affect cell signaling, membrane structure, and energy production, highlighting the pathway’s significance in health and disease.