Meaney S, Hassan M, Sakinis A, Lütjohann D, von Bergmann K, Wennmalm A, Diczfalusy U, Björkhem I
Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, SE-141 86 Huddinge, Sweden.
J Lipid Res. 2001 Jan;42(1):70-8.
The major oxysterols in human circulation are 7 alpha-, 27-, and (24S)-hydroxycholesterol. Two unique experiments were performed to elucidate their origin and kinetics. A volunteer was exposed to (18)O(2)-enriched air. A rapid incorporation of (18)O in both 7 alpha- and 27-hydroxycholesterol and disappearance of label after exposure were observed. The half-life was estimated to be less than 1 h. Incorporation of (18)O in (24S)-hydroxycholesterol was not significant. In the second experiment a volunteer was infused with liposomes containing 10 g of [(2)H(6)]cholesterol. This resulted in an enrichment of plasma cholesterol with (2)H of up to 13%, and less than 0.5% in cerebrospinal fluid cholesterol. The content of (2)H in circulating 7 alpha-hydroxycholesterol remained approximately equal to that of plasma cholesterol and decreased with a half-life of about 13 days. The (2)H 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 (2)H in (24S)-hydroxycholesterol was observed. It is evident that 7 alpha-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, A. 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.
人体循环中的主要氧化甾醇是7α-、27-和(24S)-羟基胆固醇。进行了两项独特的实验以阐明它们的来源和动力学。一名志愿者暴露于富含(18)O₂的空气中。观察到(18)O在7α-和27-羟基胆固醇中快速掺入，且暴露后标记消失。半衰期估计小于1小时。(18)O在(24S)-羟基胆固醇中的掺入不显著。在第二项实验中，给一名志愿者输注含有10 g [(2)H₆]胆固醇的脂质体。这导致血浆胆固醇中(2)H的富集高达13%，而脑脊液胆固醇中(2)H的富集小于0.5%。循环中的7α-羟基胆固醇中(2)H的含量与血浆胆固醇的含量大致相等，且以约13天的半衰期下降。循环中的27-羟基胆固醇中(2)H的含量最初低于胆固醇，但在实验的最后阶段超过了胆固醇。未观察到(2)H在(24S)-羟基胆固醇中有显著掺入。显然，7α-羟基胆固醇必定源自一个快速混合池，约80%的27-羟基胆固醇源自一个交换较慢的池，而超过90%的(24S)-羟基胆固醇源自一个不可交换池，大概是大脑。结合氧化甾醇在胆固醇稳态中的作用及其作为病理状况标志物的用途对结果进行了讨论。——米尼，S.，M. 哈桑，A. 萨基尼斯，D. 吕特约翰，K. 冯·伯格曼，A. 温马尔姆, U. 迪茨法卢西，以及I. 比约克姆。人体循环中主要氧化甾醇源自不同胆固醇池的证据：一项稳定同位素研究。《脂质研究杂志》。2001年。42: 70 - 78。
