Esterification and absorption of cholesterol: in vitro and in vivo observations in the rat |
| |
Authors: | R J Williams A D McCarthy C D Sutherland |
| |
Institution: | Department of Biochemistry, Glaxo Group Research Ltd., Greenford, Middlesex, U.K. |
| |
Abstract: | 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. |
| |
Keywords: | |
|
|