Inhibition of acyl coenzyme A: Cholesterol acyltransferase by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

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Abstract
Relatively high concentrations of MK-733 (simvastatin) and MK-803 (lovastatin, mevinolin), which are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, were found to inhibit acyl coenzyme A: cholesterol acyltransferase (ACAT) of rabbit intestinal microsomes with IC50''s of 2.0 .times. 10-5 and 3.6 .times. 10-5 M, respectively. Dihydroxy acid forms of both MK-733 and MK-803 did not inhibit ACAT activity. A kinetic analysis using a Lineweaver-Burk plot indicated that MK-733 is a competitive inhibitor of ACAT, with a Ki value of 1.2 .times. 10-5 M.