FIGURE 2.

Cholesterol biosynthesis pathway and principal inhibitors. Starting from three molecules of acetyl-coenzyme A (CoA), cholesterol is synthesized in more than 20 enzymatic steps. 3-Hydroxy-3-methylglutaryl-CoAreductase (HMGCR) and squalene epoxidase (SQLE) act as rate-limiting enzymes. The principal inhibitors of cholesterol biosynthesis are statins that inhibit HMGCR, inhibitors of sterol regulating binding protein (SREBP) that inactivate the transcription of cholesterol biosynthesis genes; and bisphosphonates that act downstream of statins and inhibit farnesyl pyrophosphate synthase with consecutive decrease of the farnesyl pyrophosphate and geranylgeranyl pyrophosphate. This step of the cholesterol biosynthesis is also targeted by farnesyl transferase inhibitors.