The conversion of the two-carbon acetyl-CoA to the twenty-seven-carbon, tetracyclic cholesterol via the mevalonate pathway is a remarkable feat of anabolic engineering. Its earliest steps yield mevalonate, followed by isoprenoid precursors that condense to produce the squalene backbone of cholesterol (Fig. 1). Oxygenation and cyclization form the steroid nucleus, upon which the pathway bifurcates into two parallel branches, Bloch and Kandutsch-Russell, each involving successive rounds of reduction and demethylation.
