Mevalonate pathway

Route: 3-Hydroxy-3-methylglutaryl-CoA → Mevalonate → Mevalonate 5-phosphate → Mevalonate 5-diphosphate → Isopentenyl diphosphate + Dimethylallyl diphosphate

HMG-CoA reductase uses two NADPH to turn the thioester of HMG-CoA into the alcohol mevalonate and releases CoA. It is the target of the statin drugs, which occupy part of the HMG-CoA binding site and block access to the active site. Mevalonate kinase and phosphomevalonate kinase add two phosphate groups from ATP, one at a time. Diphosphomevalonate decarboxylase then uses a third ATP, removes CO₂ and the phosphate on carbon 3, and makes the double bond of isopentenyl diphosphate (IPP). Isopentenyl diphosphate isomerase moves that double bond and gives dimethylallyl diphosphate (DMAPP). IPP and DMAPP are the five-carbon units from which cells build cholesterol and many other isoprenoids. Cholesterol continues from here through many more steps, which are not shown. This is the cytosolic route in animals, where the HMG-CoA comes from a cytosolic synthase. Bacteria such as E. coli use a different route to IPP and DMAPP.

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Steps

Enzyme names and EC numbers are those used on the interactive board. Checked against sources: see the claim table in the repository (tools/pathway_data/checks).