Tani M, Goto J, Makino I
Second Department of Internal Medicine, Asahikawa Medical College, Japan.
J Gastroenterol. 1994 Oct;29(5):621-30. doi: 10.1007/BF02365446.
We conducted in vivo and in vitro studies of the reductive metabolism of the cholagogue, dehydrocholic acid (DHCA). Immediately after the intravenous administration of 1 g of DHCA in normal subjects (n = 6), the concentration of the reductive metabolite, 3 alpha-hydroxy-7,12-dioxo-cholanoic acid (unconjugated form), increased sharply in the systemic circulation, rising to 95.8 microM 10 min after administration. The results of in vitro experiments with DHCA and whole blood showed that 3 alpha-hydroxy-7,12-dioxocholanoic acid were produced from DHCA. In vitro experiments using DHCA and the red blood cell fraction, and DHCA and the red blood cell cytoplasmic fraction gave similar results to those described above with whole blood. However, a reductive metabolite was not formed by the incubation of DHCA and the red blood cell membrane fraction. These findings indicated that, contrary to the conventional theory that intravenously administered DHCA is subjected to reductive metabolism only in the liver, reduction also occurs in the systemic circulation, and the mechanism for this reductive metabolism is present in the cytoplasmic fraction of red blood cells. Further investigation to characterize this reductive metabolic system revealed an optimum temperature of 37 degrees C, an optimum pH of 7.4, a Km value of 2.0 x 10(-3) M, and inactivation by heat treatment (70 degrees C for 2 min).
我们对利胆剂脱氢胆酸（DHCA）的还原代谢进行了体内和体外研究。在正常受试者（n = 6）静脉注射1 g DHCA后，还原代谢产物3α-羟基-7,12-二氧代胆烷酸（未结合形式）的浓度在体循环中急剧增加，给药后10分钟升至95.8 μM。用DHCA和全血进行的体外实验结果表明，DHCA可产生3α-羟基-7,12-二氧代胆烷酸。使用DHCA与红细胞组分以及DHCA与红细胞胞质组分进行的体外实验得到了与上述全血实验相似的结果。然而，DHCA与红细胞膜组分孵育未形成还原代谢产物。这些发现表明，与传统理论认为静脉注射的DHCA仅在肝脏中进行还原代谢相反，体循环中也会发生还原反应，且这种还原代谢的机制存在于红细胞的胞质组分中。进一步表征这种还原代谢系统的研究表明，其最适温度为37℃，最适pH为7.4，Km值为2.0×10⁻³ M，且经热处理（70℃ 2分钟）会失活。
