Salen G, Shore V, Tint G S, Forte T, Shefer S, Horak I, Horak E, Dayal B, Nguyen L, Batta A K
Medical Service, Veterans Administration Medical Center, East Orange, NJ 07019.
J Lipid Res. 1989 Sep;30(9):1319-30.
We measured the turnover and absorption of sitosterol and cholesterol, along with plasma sterol and lipoprotein concentrations, in one control and two subjects with sitosterolemia with xanthomatosis. All individuals consumed the same diet which contained approximately 500 mg/day of cholesterol and 250 mg/day of sitosterol. Sterol absorption was measured by the plasma dual-isotope ratio method and turnover by plasma isotope-kinetic analysis. In two sitosterolemic subjects, 28% and 63% of the sitosterol and 69% and 49% of the cholesterol were absorbed, respectively, compared to 4% of the sitosterol and 44% of the cholesterol in the control. As expected, plasma sitosterol specific activities decayed much more rapidly than cholesterol in the control subject. In contrast, plasma sitosterol and cholesterol specific activity-time curves were similar and decayed more slowly in the sitosterolemic subjects. In the control subject, the total sitotterol pool was 290 mg and was linearly related to low absorption (18 mg/day); whereas the total sitosterol pool was 17 times (4800 mg) and 13 times (3500 mg) larger, respectively, in the sitosterolemic subjects and was expanded out of proportion to increased absorption because of decreased removal. Daily cholesterol turnover and synthesis were markedly reduced in the sitosterolemic subjects. In four sitosterolemic subjects, plasma concentrations of total sterols, low density lipoproteins, and apolipoprotein B were increased, while those of high density lipoproteins and apolipoprotein A-I were low to normal. The low density lipoproteins were very similar to those of normal control subjects in density distribution, peak flotation rate, sterol-to-protein (apolipoprotein B) ratio, particle size, and morphology. These results demonstrate in patients with sitosterolemia with xanthomatosis that: 1) the absorption of sitosterol and cholesterol is enhanced; 2) tissue recognition between cholesterol and sitosterol is lost; 3) total exchangeable sitosterol pools are expanded out of proportion to absorption because of decreased excretion; 4) plasma sterol and lipoprotein concentrations favor tissue deposition; and 5) cholesterol synthesis is diminished. We postulate that the changes in sitosterol metabolism (increased absorption, loss of tissue sterol structural recognition, expanded pools, and hepatic retention) are a response to reduced cholesterol synthesis in these subject.
我们测量了一名对照者以及两名患有黄瘤病的谷甾醇血症患者体内谷甾醇和胆固醇的周转率及吸收率，同时还测量了血浆甾醇和脂蛋白浓度。所有个体均食用相同饮食，其中每天约含500毫克胆固醇和250毫克谷甾醇。采用血浆双同位素比率法测量甾醇吸收率，通过血浆同位素动力学分析测量周转率。在两名谷甾醇血症患者中，谷甾醇的吸收率分别为28%和63%，胆固醇的吸收率分别为69%和49%，而对照者中谷甾醇的吸收率为4%，胆固醇的吸收率为44%。正如预期的那样，对照者血浆谷甾醇比活性的衰减速度比胆固醇快得多。相比之下，谷甾醇血症患者的血浆谷甾醇和胆固醇比活性-时间曲线相似，且衰减更慢。在对照者中，总谷甾醇池为290毫克，与低吸收率（18毫克/天）呈线性相关；而在谷甾醇血症患者中，总谷甾醇池分别大17倍（4800毫克）和13倍（3500毫克），且由于清除减少，其扩张与吸收率增加不成比例。谷甾醇血症患者的每日胆固醇周转率和合成量明显降低。在四名谷甾醇血症患者中，总甾醇、低密度脂蛋白和载脂蛋白B的血浆浓度升高，而高密度脂蛋白和载脂蛋白A-I的血浆浓度则处于低至正常水平。低密度脂蛋白在密度分布、峰值漂浮率、甾醇与蛋白质（载脂蛋白B）比率、颗粒大小和形态方面与正常对照者非常相似。这些结果表明，在患有黄瘤病的谷甾醇血症患者中：1）谷甾醇和胆固醇的吸收增强；2）胆固醇与谷甾醇之间的组织识别丧失；3）由于排泄减少，可交换的总谷甾醇池扩张与吸收不成比例；4）血浆甾醇和脂蛋白浓度有利于组织沉积；5）胆固醇合成减少。我们推测，谷甾醇代谢的变化（吸收增加、组织甾醇结构识别丧失、池扩张和肝脏潴留）是这些受试者胆固醇合成减少的一种反应。
