Rosuvastatin Pathway


Rosuvastatin 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. The active form of statins bears a chemical resemblance to the reduced HMG-CoA reaction intermediate that is formed during catalysis. Structure-activity relationship studies have demonstrated that statins bind to HMG-CoA reductase at the same site as the reduced intermediate and are held in place by similar chemical interactions. Unlike Lovastatin and simvastatin, which undergo in vivo hydrolysis to their active form rosuvastatin is synthetically produced in active form. Cholesterol biosynthesis accounts for approximately 80% of cholesterol in the body; thus, inhibiting this process can significantly lower cholesterol levels.

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References

  1. Crestor. (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.