Cardiology
-
The microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase is a key rate-controlling step early in the cholesterol biosynthetic pathway that catalyzes the conversion of HMG CoA to mevalonic acid. Since this enzyme plays a significant role in regulating cholesterol synthesis, it is a rational target for pharmacologic intervention. The first potent, specific inhibitor of HMG CoA was mevastatin (compactin, ML-236B), which was discovered in 1976 by Endo et al. [J Antibiot 1976:29:1346-1348]. ⋯ Associated with the cholesterol lowering is a decrease in urinary and plasma levels of mevalonic acid, the end product of the HMG CoA reductase reaction. The target organ for inhibitors of HMG CoA reductase is the liver, the primary site of cholesterol biosynthesis. Both lovastatin and simvastatin are preferentially extracted by this organ.(ABSTRACT TRUNCATED AT 250 WORDS)