出版社：American Society for Biochemistry and Molecular Biology
摘要：The major oxysterols in human circulation are 7α-, 27-, and (24 S )-hydroxycholesterol. Two unique experiments were performed to elucidate their origin and kinetics. A volunteer was exposed to 18O2-enriched air. A rapid incorporation of 18O in both 7α- and 27-hydroxycholesterol and disappearance of label after exposure were observed. The half-life was estimated to be less than 1 h. Incorporation of 18O in (24 S )-hydroxycholesterol was not significant. In the second experiment a volunteer was infused with liposomes containing 10 g of [2H6]cholesterol. This resulted in an enrichment of plasma cholesterol with 2H of up to 13%, and less than 0.5% in cerebrospinal fluid cholesterol. The content of 2H in circulating 7α-hydroxycholesterol remained approximately equal to that of plasma cholesterol and decreased with a half-life of about 13 days. The 2H content of circulating 27-hydroxycholesterol was initially lower than that of cholesterol but in the last phase of the experiment it exceeded that of cholesterol. No significant incorporation of 2H in (24 S )-hydroxycholesterol was observed. It is evident that 7α-hydroxycholesterol must originate from a rapidly miscible pool, about 80% of 27-hydroxycholesterol from a more slowly exchangeable pool, and more than 90% of (24 S )-hydroxycholesterol from a nonexchangeable pool, presumably the brain. The results are discussed in relation to the role of oxysterols in cholesterol homeostasis and their use as markers for pathological conditions. —Meaney, S., M. Hassan, A. Sakinis, D. Lütjohann, K. von Bergmann, Å. Wennmalm, U. Diczfalusy, and I. Björkhem. Evidence that the major oxysterols in human circulation originate from distinct pools of cholesterol: a stable isotope study. J. Lipid Res. 2001. 42: 70–78.
