Generation of plasma free cholesterol from circulating lipoprotein-associated cholesteryl ester.
Studies were performed to investigate the contribution of lipoprotein-associated cholesteryl ester (CE) in the monkey to circulating free cholesterol (FC). Monkey plasma was incubated with [14C]- or [3H]cholesteryl ester, and radiolabeled low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were isolated by ultracentrifugation. Animals received labeled LDL or HDL. A rapid transfer of CE between lipoproteins was observed, consistent with an active CE transfer protein activity in the monkey. Within 4 h the percent of plasma radioactivity in FC after injection of CE-labeled LDL or HDL was, respectively, 30 and 7% of that of the ester. To determine whether the generation of FC was due to a circulating plasma cholesteryl ester hydrolase, monkey plasma was incubated with CE-labeled lipoproteins with and without 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). A small amount of FC (less than 3% of the radioactivity) was generated during this incubation but most of the FC production was inhibited by DTNB. Although a small amount of FC can be produced by a plasma cholesteryl esterase (perhaps via reverse action of lecithin-cholesterol acyltransferase), most of the FC in plasma derived from lipoprotein-associated CE is probably due to tissue uptake of lipoproteins and subsequent intracellular hydrolysis of the CE to produce FC.
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism*; D006023:Glycoproteins; D006868:Hydrolysis; D008074:Lipoproteins / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D002787:Sterol Esterase / Q000378:metabolism
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C039160:lipoprotein cholesterol ester, human; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D002787:Sterol Esterase