The synthesis of cholesterol through the hydroxymethyl-coenzyme A reductase.
The synthesis of cholesterol occurs in the cytoplasm of liver cells and intestine mainly. The synthesis begins with condensation of three molecules of acetate (3 × 2 = carbon) to hydroxy-methyl-glutarate (HMG or = 1 × 6 carbon moiety). This synthesis is performed by the hydroxymethylglutaryl coenzyme A synthase (or HMGCoA synthase), an enzyme in the presence of coenzyme A, an enzyme cofactor. The hydroxy-methyl-glutarate is then reduced to mevalonate (= 1 × 6 carbons). This step is regulated by statins. The mevalonate is then decarboxylated to 5-carbon isoprenoids (isopentenyl pyrophosphate and dimethylallyl pyrophosphate). Condensation of 6 molecules ultimately results in isoprenoid squalene (6 x 5 = 30 carbons). Finally, squalene is undergoing the action of squalene cyclase which creates cycles of cholesterol from unsaturation present in squalene.
