mevalonic

Mevalonic acid, also called mevalonate, is a hydroxy acid and a central intermediate in the mevalonate pathway, a biosynthetic route used by many organisms to produce isoprenoids, including cholesterol in animals. In humans and other eukaryotes, acetyl-CoA is converted to HMG-CoA and then reduced by HMG-CoA reductase to mevalonate, a step that is tightly regulated and the principal site of action for statin drugs. Mevalonate is then phosphorylated by mevalonate kinase, converted to mevalonate-5-phosphate, further phosphorylated to mevalonate-5-diphosphate, and decarboxylated to isopentenyl pyrophosphate (IPP). IPP and its isomer dimethylallyl pyrophosphate (DMAPP) serve as universal building blocks for isoprenoids. Through successive condensations, these units produce longer chain lipids such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are precursors for cholesterol, ubiquinone, dolichol, and various terpenoids.

Mevalonate also contributes to protein prenylation and other post-translational modifications via its diphosphate derivatives, influencing membrane association and signaling. Defects in the mevalonate pathway, such as mevalonate kinase deficiency, can cause autoinflammatory syndromes and metabolic disorders, including mevalonic aciduria. Pharmacological inhibition of HMG-CoA reductase with statins reduces mevalonate production and is a common strategy to lower cholesterol levels.

The pathway is present in most eukaryotes and some bacteria and archaea, with variations in subcellular localization. Some organisms utilize the non-mevalonate (MEP/DOXP) pathway to synthesize IPP instead of the mevalonate route.