TRANSPORT OF SIDE-CHAIN OXIDIZED OXYSTEROLS IN THE HUMAN CIRCULATION

To study the transport of 24-hydroxycholesterol, 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid in the circulation, the distri bution of these oxysterols was determined in plasma, very low density lipoprotein, low density lipoprotein, high density lipoprotein, and li poprotein-free plasma, An accurate method based on isotope dilution-ma ss spectrometry with use of individual deuterium labeled internal stan dards was used, 24-Hydroxycholesterol and 27-hydroxycholesterol were f ound to be associated mainly with HDL and LDL, whereas 3 beta-hydroxy- 5-cholestenoic acid was found predominantly in the lipoprotein-free fr action. While both 24-hydroxycholesterol and 27-hydroxycholesterol are present mainly in esterified form in plasma, 3 beta-hydroxy-5-cholest enoic acid was present as free acid only. For reasons of comparison, a number of other oxysterols were determined in plasma and in isolated lipoprotein fractions, Significant amounts of these oxysterols were fo rmed by cholesterol autoxidation during fractionation of plasma. It wa s therefore not possible to calculate the distribution of these oxyste rols in the different plasma fractions. The present results are consis tent with our previous finding that the less polar cholesterol metabol ite 27-hydroxycholesterol competes with cholesterol for transport out of cells using HDL as an acceptor molecule, whereas the transport of t he more polar compound 3 beta-hydroxy-5-cholestenoic acid is facilitat ed by albumin. (C) 1998 Elsevier Science B.V.