Lovastatin Pathway


Lovastatin, an antilipemic agent produced by fermentation of Aspergillus terreus, is the first of a class of lipid-lowering agents known as the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. HMG-CoA catalyzes the conversion of HMG-CoA to mevalonic acid, the rate-limiting step of cholesterol biosynthesis. Lovastatin, like simvastin, is a prodrug. These prodrugs are converted to their active form by in vivo hydrolysis of the lactone ring. The hydrolyzed lactone ring resembles the tetrahedral reaction intermediate produced by HMG-CoA reductase and the bicyclic portions of these compounds bind to the coenzyme A site of the enzyme. The active drug concentrates in the liver during first-pass circulation. Cholesterol biosynthesis accounts for approximately 80% of cholesterol in the body; thus, inhibiting this process can significantly lower cholesterol levels. Lovastatin is used to treat hypercholesterolemia, to slow coronary atherosclerosis, and to prevent myocardial infarction and stroke.

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References

  1. Mevacor. (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.