REGULATION OF BILE-ACID SYNTHESIS IN MAN - PRESENCE OF A DIURNAL RHYTHM
REGULATION OF BILE-ACID SYNTHESIS IN MAN - PRESENCE OF A DIURNAL RHYTHM
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DOI：
10.1172/jci111157
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发表时间：
1983-01-01
影响因子：
15.9
通讯作者：
BEHRENS, JC
中科院分区：
文献类型：
--
作者：
DUANE, WC;LEVITT, DG;BEHRENS, JC
人类对胆汁酸合成的调节尚不完全清楚，部分原因是在肠-肝循环完整的短时间内难以进行测量。研究了给予[26-14C]胆固醇的3名受试者胆汁酸合成昼夜节律的可能性。当这种在26和27位随机标记的胆固醇同位素转化为胆汁酸时，14C被释放为在1和3位随机标记的丙酸。然后标记的丙酸被氧化成14CO2，其输出是胆汁酸合成的函数。然而，相对于现有的胆汁酸合成昼夜节律，14C通过丙酸和CO2-HCO3-池的传输延迟会改变14CO2的相态，并抑制14CO2输出的幅度。因此，采用恒定输液法测定了[1-14C]丙酸和[3-14C]丙酸转化为14CO2的转化常数分别为0.36-0.59h-1和0.14-0.16h-1。利用这些常数并将昼夜节律建模为余弦函数，[26-14C]胆固醇产生的~(14)CO_2的幅度比胆汁酸合成的昼夜节律延迟2.4~3.0h，幅度降低了35%。[26-14C]胆固醇产生~(14)CO_2的昼夜节律不是由丙酸或CO_2-HCO_3代谢的日变化引起的，而是由于[1-~14C]丙酸和[3-14C]丙酸持续输注30h后表现为~(14)CO_2的日变化。这些研究首次证明，具有完整的肠-肝循环的人类胆汁酸合成的昼夜节律幅度为.+-。在平均合成附近有35-55%，在apprx附近有一个顶相。0900h。
Regulation of bile acid synthesis in man is incompletely understood, in part because of difficulty in making measurements over short time periods when the enterohepatic circulation is intact. The possibility of a diurnal rhythm of bile acid synthesis was investigated in 3 human subjects given [26-14C]cholesterol. When this isotope of cholesterol, which is randomly labeled in the 26 and 27 positions, is converted to bile acid, the 14C is released as propionic acid randomly labeled in the 1 and 3 positions. The labeled propionic acid is then oxidized to 14CO2, output of which is a function of bile acid synthesis. However, delays in transit of the 14C through propionic acid and CO2-HCO3- pools would shift the phase and dampen the amplitude of 14CO2 output relative to an existing diurnal rhythm of bile acid synthesis. Therefore, using constant infusion methods, the turnover constants for conversion to 14CO2 of [1-14C]propionic acid and [3-14C]propionic acid were determined to be 0.36-0.59 h-1 and 0.14-0.16 h-1, respectively. Using these constants and modeling the diurnal rhythm as a cosine function, the amplitude of 14CO2 output from [26-14C]cholesterol was reduced 35% and acrophase was delayed 2.4-3.0 h relative to the diurnal rhythm of bile acid synthesis. None of the diurnal rhythm in 14CO2 output from [26-14C]cholesterol resulted from diurnal variation in propionic acid or CO2-HCO3- metabolism since constant infusion of [1-14C]propionic acid and [3-14C]propionic acid for 30 h revealed into diurnal variation in output of 14CO2. These studies demonstrate for the 1st time that humans with an intact enterohepatic circulation have a diurnal rhythm of the bile acid synthesis with an amplitude of .+-. 35-55% around mean synthesis, and a acrophase at .apprx. 0900h.