Mevalonate pathway

Overview
The mevalonate pathway or HMG-CoA reductase pathway or mevalonate-dependent (MAD) route, is an important cellular metabolic pathway present in all higher eukaryotes and many bacteria. It is important for the production of dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP), which serve as the basis for the biosynthesis of molecules used in processes as diverse as protein prenylation, cell membrane maintenance, hormones, protein anchoring, and N-glycosylation. It is also a part of steroid biosynthesis.

Regulation and feedback
Several key enzymes can be activated through DNA transcriptional regulation on activation of SREBP (Sterol Regulatory Element-Binding Protein-1 and -2). This intracellular sensor detects low cholesterol levels and stimulates endogenous production by the HMG-CoA reductase pathway, as well as increasing lipoprotein uptake by up-regulating the LDL receptor. Regulation of this pathway is also achieved by controlling the rate of translation of the mRNA, degradation of reductase and phosphorylation.


 * For more information on regulation, see HMG-CoA reductase

Pharmacology
A number of drugs target the mevalonate pathway:
 * Statins (used for elevated cholesterol levels);
 * Bisphosphonates (used in treatment of various bone-degenerative diseases)

Alternative
Plants and apicomplexan protozoa such as malaria parasites have the ability to produce their isoprenoids (terpenoids) using an additional alternative pathway called the methylerythritol phosphate (MEP) or non-mevalonate pathway, which takes place in their plastids. In addition, most eubacteria including important pathogens, such as Mycobacterium tuberculosis, synthesize IPP and DMAPP via the non-mevalonate pathway instead.