27-hydroxycholesterol: production rates in normal human subjects.

27-hydroxycholesterol: production rates in normal human subjects.
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DOI:
10.1016/s0022-2275(20)33481-7
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发表时间:
1999-07
影响因子:
6.5
通讯作者:
W. Duane;N. Javitt
W. Duane;N. Javitt
中科院分区:
生物学2区
文献类型:
--
作者:
W. Duane;N. Javitt

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我们尝试定量 6 名人类受试者通过 27-羟基化途径产生的胆汁酸。静脉推注已知量的[24-14C]胆酸和[24-14C]鹅去氧胆酸后,每个受试者持续静脉输注[22,23-3H]-27-羟基胆固醇和[2H]-27-羟基胆固醇的混合物6-10小时。 27-羟基胆固醇的生成率根据[2H]-27-羟基胆固醇的输注速率和氘化/氕27-羟基胆固醇的血清比率计算,在输注4小时时达到平台水平。 27-羟基胆固醇向胆酸和鹅去氧胆酸的转化由输注后第二天获得的胆汁样品中这两种胆汁酸的 3 H/ 14 C比率确定。在六名受试者中的五名中,从以前的研究中可以通过粪便酸性甾醇输出独立测量胆汁酸合成。 27-羟基胆固醇的内源产量平均为 17.6 毫克/天,范围为 5.0 至 28.2 毫克/天,占总胆汁酸合成的 8.7%(范围为 3.0-17.9%)。平均 66% 的输注 27-羟基胆固醇转化为胆汁酸,其中 72.6% 是鹅去氧胆酸。这些数据表明,健康人中通过 27-羟基化途径进行的胆汁酸合成相对较少。然而,即使这个量主要存在于血管内皮和巨噬细胞中,也可能代表去除沉积在内皮中的胆固醇的重要手段。-Duane, W. C., 和 N. B. Javitt.27-羟基胆固醇:正常人类受试者的生产率。脂质研究 1999。 40:1194-1199。
We attempted to quantitate production of bile acid via the 27-hydroxylation pathway in six human subjects. After bolus intravenous injection of known amounts of [24-14C]cholic acid and [24-14C]chenodeoxycholic acid, each subject underwent a constant intravenous infusion of a mixture of [22,23-3H]-27-hydroxycholesterol and [2H]-27-hydroxycholesterol for 6–10 h. Production rate of 27-hydroxycholesterol was calculated from the infusion rate of [2H]-27-hydroxycholesterol and the serum ratio of deuterated/protium 27-hydroxycholesterol, which reached a plateau level by 4 h of infusion. Conversion of 27-hydroxycholesterol to cholic and chenodeoxycholic acids was determined from the3H/14C ratio of these two bile acids in bile samples obtained the day after infusion. In five of the six subjects, independent measurement of bile acid synthesis by fecal acidic sterol output was available from previous studies. Endogenous production of 27-hydroxycholesterol averaged 17.6 mg/day and ranged from 5.0 to 28.2 mg/day, which amounted to 8.7% (range 3.0–17.9%) of total bile acid synthesis. On average 66% of infused 27-hydroxycholesterol was converted to bile acid, of which 72.6% was chenodeoxycholic acid. These data suggest that relatively little bile acid synthesis takes place via the 27-hydroxylation pathway in healthy humans. Nevertheless, even this amount, occurring predominantly in vascular endothelium and macrophages, could represent an important means for removal of cholesterol deposited in endothelium.—Duane, W. C., and N. B. Javitt.27-Hydroxycholesterol: production rates in normal human subjects.J. Lipid Res.1999. 40: 1194–1199.