Regulation of acyl CoA:cholesterol acyltransferase by 25-hydroxycholesterol in rabbit intestinal microsomes and absorptive cells.
The regulation of rabbit intestinal acyl CoA:cholesterol acyltransferase (ACAT) by 25-hydroxycholesterol was studied. 25-Hydroxycholesterol significantly increased jejunal microsomal ACAT activity. The stimulation of ACAT activity by 25-hydroxycholesterol was inversely related to microsomal cholesterol content. In enterocytes, 25-hydroxycholesterol stimulated cholesteryl ester synthesis 6-fold. The esterification of cholesterol, taken up by enterocytes from liposomes or bile salt micelles, was increased by 25-hydroxycholesterol. This, however, did not affect the rate of uptake of cholesterol by the cells. In intestinal cells from rabbits fed cholesterol, the effect of 25-hydroxycholesterol on cholesteryl ester synthesis was 50% of that in cells prepared from animals fed no cholesterol. 25-Hydroxycholesterol stimulated the esterification of newly synthesized cholesterol. As new free cholesterol increased in enterocytes, 25-hydroxycholesterol lost its effect. Despite large amounts of newly synthesized cholesterol, oleic acid incorporation into cholesteryl ester was not increased. We conclude that 25-hydroxycholesterol increases intestinal ACAT activity. The effect of 25-hydroxycholesterol on ACAT is dependent upon the availability of cholesterol to the enzyme. At cholesterol concentrations below saturation, the oxygenated sterol has a stimulatory effect. If ACAT is saturated, 25-hydroxycholesterol has no effect. ACAT catalyzes the esterification of two separate pools of cholesterol within the enterocyte, i.e., newly synthesized cholesterol and membrane cholesterol. 25-Hydroxycholesterol increases the esterification rate of cholesterol in both pools.
D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D002788:Cholesterol Esters / Q000378:metabolism; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007422:Intestines / Q000187:drug effects / Q000201:enzymology*; D050356:Lipid Metabolism; D008297:Male; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D011817:Rabbits; D002785:Sterol O-Acyltransferase / Q000378:metabolism*
D002788:Cholesterol Esters; D006888:Hydroxycholesterols; D009829:Oleic Acids; D019301:Oleic Acid; C015367:mevalonolactone; C007997:25-hydroxycholesterol; D000217:Acyltransferases; D002785:Sterol O-Acyltransferase; D008798:Mevalonic Acid