Esterification and absorption of cholesterol: in vitro and in vivo observations in the rat.
Activity of the enzyme acyl-CoA:cholesterol acyltransferase (ACAT) in isolated rat enterocytes was reduced by approx. 75% following a single oral dose of Sandoz compound 58-035 (30 mg.kg-1). Despite this, the formation of [14C]cholesteryl esters from [1-14C]oleic acid remained unaffected in ACAT-inhibited cell preparations. The increase in serum cholesterol concentrations observed after overnight cholesterol/cholic acid (1%/0.5%) feeding to rats was abolished by pre-treatment with Sandoz compound 58-035 (30 mg.kg-1). These results can be reconciled with a previously proposed model for the transmembrane movement of cholesterol which implicates ACAT-independent esterification and hydrolysis as a transport mechanism for the movement of cholesterol across the enterocyte apical membrane.
Williams
R J
RJ
Department of Biochemistry, Glaxo Group Research Ltd., Greenford, Middlesex, U.K.
McCarthy
A D
AD
Sutherland
C D
CD
D000577:Amides / Q000494:pharmacology; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000096:biosynthesis; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D008297:Male; D017646:Organosilicon Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000502:physiology*
D000577:Amides; D002788:Cholesterol Esters; D017646:Organosilicon Compounds; C040256:SAN 58035; D002784:Cholesterol; D002785:Sterol O-Acyltransferase