METABOLISM OF CHOLESTANOL AND CHOLESTEROL IN MAN

本研究的目的是检查胆固醇和胆甾烷醇 在肌腱黄瘤病（CTX）患者中的代谢， 动脉粥样硬化和胆结石。 特别地，我们将继续定义 罕见遗传性脂质储存的临床和生化异常 疾病，CTX。 在CTX中，胆汁酸合成的缺陷导致过量的 胆固醇和胆甾烷醇的产生和组织积累。 一个主要 目的是抑制异常的胆汁酸合成途径， 鹅去氧胆酸，并评估临床和生化变化 病程。 此外，胆甾烷醇形成的位点及其 监管将被调查。 此外，侧链的途径 将检查胆固醇氧化成胆汁酸以确定是否 侧链裂解通过26-或25-羟基化衍生物进行。 在其他实验中，植物甾醇（菜油甾醇和 谷固醇）和胆固醇将在谷固醇血症中进行评估， 黄瘤病是一种新发现的植物脂质沉积病， 甾醇（菜油甾醇和谷甾醇）沿着胆固醇积累在 身体 我们打算测量谷甾醇和胆固醇周转的 同位素动力学方法，谷甾醇转化为胆汁酸和 评估谷甾醇和胆固醇的肠道吸收， 血浆双同位素比值法，不依赖于粪便平衡 测量.

The aim of this investigation is to examine cholesterol and cholestanol metabolism in patients with cerebrotendinous xanthomatosis (CTX), atherosclerosis and gallstones. Specially we shall continue to define the clinical and biochemical abnormalities in the rare inherited lipid storage diseases, CTX. In CTX, a defect in bile acid synthesis leads to excessive production and tissue accumulation of cholesterol and cholestanol. A major goal is to suppress the abnormal bile acid synthetic pathway with chenodeoxycholic acid and evaluate changes in the clinical and biochemical course of the disease. Further the site of cholestanol formation and its regulation will be investigated. In addition, the pathway of side chain oxidation of cholesterol to bile acid will be examined to determine whether the side chain cleavage proceeds via 26- or 25-hydroxylated derivatives. In other experiments, the metabolism of plant sterols (campesterol and sitosterol) and cholesterol will be evaluated in sitosterolemia with xanthomatosis, a newly discovered lipid storage disease in which plant sterols (campesterol and sitosterol) along with cholesterol accumulate in the body. We intend to measure sitosterol and cholesterol turnover by the isotope kinetic method, conversion of sitosterol to bile acids and to assess the intestinal absorption of both sitosterol and cholesterol by the plasma dual isotope ratio method, which is not dependent on fecal balance measurements.