BILE-ACID SYNTHESIS IN MAN - INVIVO ACTIVITY OF THE 25-HYDROXYLATION PATHWAY
BILE-ACID SYNTHESIS IN MAN - INVIVO ACTIVITY OF THE 25-HYDROXYLATION PATHWAY
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DOI：
10.1172/jci113605
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发表时间：
1988-07-01
影响因子：
15.9
通讯作者：
HAMILTON, JN
中科院分区：
文献类型：
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作者：
DUANE, WC;POOLER, PA;HAMILTON, JN
在胆汁酸的生物合成过程中，胆固醇侧链上的碳25-26-27被去除。侧链氧化开始于26位的羟基化，在这种情况下，三碳片段作为丙酸释放，或者开始于25位的羟基化，在这种情况下，三碳片段作为丙酮释放。我们以前已经表明，在大鼠中，25-羟基化途径的贡献可以在体内通过测量[14 C]26-胆固醇的[14 C]丙酮的产生来定量。在本研究中，我们将这种方法应用于人类受试者。口服100 μ Ci [14 C]26-胆固醇后4天和开始恒定输注16.6 μ mol/min未标记丙酮后1天，三名男性和两名女性进行呼吸收集。捕集呼出的丙酮并纯化为2，4-二硝基苯肼衍生物。用苯乙胺定量捕集~（14）CO_2。呼吸丙酮的比活度乘以丙酮输注速率以计算[14 C]丙酮的产生。[14 C]丙酮的生成量平均占[14 C]26-胆固醇释放的14 C总量的4.9%，由14 CO2输出量估算。通过显示[14 C]异丙醇的[14 C]丙酮产量平均为[14 C]-异丙醇输注速率的86.9%，验证了该方法。我们的结论是，在人，在大鼠，25-羟基化途径占
During biosynthesis of bile acid, carbons 25-26-27 are removed from the cholesterol side-chain. Side-chain oxidation begins either with hydroxylation at the 26-position, in which case the three-carbon fragment is released as propionic acid, or with hydroxylation at the 25-position, in which case the three-carbon fragment is released as acetone. We have previously shown in the rat that the contribution of the 25-hydroxylation pathway can be quantitated in vivo by measuring production of [14C]acetone from [14C]26-cholesterol. In the present study, we adapted this method to human subjects. 4 d after oral administration of 100 .mu.Ci of [14C]26-cholesterol and 1 d after beginning a constant infusion of 16.6 .mu.mol/min unlabeled acetone, three men and two women underwent breath collections. Expired acetone was trapped and purified as the 2,4 dinitrophenylhydrazine derivative. 14CO2 was trapped quantitatively using phenethylamine. Specific activity of breath acetone was multiplied by the acetone infusion rate to calculate production of [14C]acetone. [14C]Acetone production averaged 4.9% of total release of 14C from [14C]26-cholesterol, estimated by 14CO2 output. The method was validated by showing that [14C]acetone production from [14C]isopropanol averaged 86.9% of the [14C]-isopropanol infusion rate. We conclude that in man, as in the rat, the 25-hydroxylation pathway accounts for