Inhibition of acyl coenzyme A: cholesterol acyltransferase by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.
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 x 10(-5) and 3.6 x 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 x 10(-5) M.
Ishida
F
F
Sato
A
A
Iizuka
Y
Y
Kamei
T
T
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011817:Rabbits; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D000214:Acyl Coenzyme A; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002785:Sterol O-Acyltransferase