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Journal of Lipid Research, Vol. 42, 70-78, January 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Evidence that the major oxysterols in human circulation originate from distinct pools of cholesterol: a stable isotope study

Correspondence to: Ingemar Björkhem, To whom correspondence should be addressed.

The major oxysterols in human circulation are 7-, 27-, and (24S)-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 7- 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 (24S)-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 7-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 (24S)-hydroxycholesterol was observed.

It is evident that 7-hydroxycholesterol must originate from a rapidly miscible pool, about 80% of 27-hydroxycholesterol from a more slowly exchangeable pool, and more than 90% of (24S)-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.

Supplementary key words: CYP7A, CYP27, CYP46, brain choles-terol, ¹⁸O study

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