Atorvastatin Pathway


Atorvastatin inhibits cholesterol synthesis via the mevalonate pathway by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is the enzyme responsible for the conversion of HMG-CoA to mevalonic acid, the rate-limiting step of cholesterol synthesis by this pathway. Atorvastatin bears a chemical resemblance to the reduced HMG-CoA reaction intermediate that is formed during catalysis. Structure-activity relationship studies have demonstrated that atorvastatin binds to HMG-CoA reductase at the same site as the reduced intermediate and are held in place by similar chemical interactions. Cholesterol biosynthesis accounts for approximately 80% of cholesterol in the body; thus, inhibiting this process can significantly lower cholesterol levels. Atorvastatin has a unique structure, long half-life, and hepatic selectivity, explaining its greater LDL-lowering potency compared to other HMG-CoA reductase inhibitors.

Pathway legend Zoom in

Pathway Image

Pathway legend Zoom in

References

  1. Lipitor. (2009). [Electronic version]. e-CPS. Retrieved June 30, 2009.
  2. Reszka, A.A., & Rodan, G.A. (2003). Bisphosphonate mechanism of action. Current Rheumatology Reports, 5(1), 65-74. PMID: 12590887
  3. Schmidt, E.B., & Larsen, M.L. (2004). HMG-CoA-reductase-inhibitors. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 460-463). Berlin, Germany: Springer.