Peters W H, Nagengast F M, van Tongeren J H
Division of Gastrointestinal and Liver Diseases, St. Radboud University Hospital, Nijmegen, the Netherlands.
Gastroenterology. 1989 Mar;96(3):783-9.
In humans, data on biotransformation enzymes in the intestine, and to a lesser extent in the liver, are rather scarce. Much knowledge about these enzymes is, therefore, obtained from animal studies. We were able to examine both small intestinal and hepatic tissue from a kidney donor and performed a systematic study on enzyme contents and distribution in these organs. In the small intestine the longitudinal distribution of cytochrome P450, glutathione S-transferase, and bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase declined from duodenum to ileum. Activity of 4-nitrophenol- and 4-methylumbelliferone UDP-glucuronosyltransferase increased or remained constant, respectively. Total and specific activity of most enzymes was much higher in the liver, except for bilirubin UDP-glucuronosyltransferase and glutathione S-transferase, where the small intestine contained 28.6% and 7.4% of total hepatic activity, respectively. The relatively great amount of bilirubin UDP-glucuronosyltransferase activity in the small intestinal mucosa of this patient, who probably suffered from Gilbert's syndrome, could indicate that under pathological conditions intestinal metabolism may contribute significantly to the clearance of bilirubin. With a monoclonal antibody, UDP-glucuronosyltransferase isoforms were immunodetectable in microsomes. In the liver, two bands, one of 57 kilodaltons and one in between 53 and 54 kilodaltons, were seen. In the proximal small intestine two isoforms (53 and 54 kilodaltons) were detected. However, in the distal small intestine where bilirubin UDP-glucuronosyltransferase activity was low, only one isoform (54 kilodaltons) was seen. This may indicate that bilirubin UDP-glucuronosyltransferase activity is correlated with the 53-kilodalton isoform. The presence of multiple UDP-glucuronosyltransferase isoforms in humans, similar to that described before in the rat, is further established by this study.
在人类中，关于肠道以及在较小程度上肝脏中的生物转化酶的数据相当匮乏。因此，关于这些酶的许多知识是从动物研究中获得的。我们能够检查一位肾供体的小肠和肝组织，并对这些器官中的酶含量和分布进行了系统研究。在小肠中，细胞色素P450、谷胱甘肽S - 转移酶和胆红素尿苷5'-二磷酸（UDP）-葡萄糖醛酸基转移酶的纵向分布从十二指肠到回肠逐渐下降。4 - 硝基苯酚和4 - 甲基伞形酮UDP - 葡萄糖醛酸基转移酶的活性分别增加或保持不变。除了胆红素UDP - 葡萄糖醛酸基转移酶和谷胱甘肽S - 转移酶外，大多数酶的总活性和比活性在肝脏中要高得多，其中小肠中的胆红素UDP - 葡萄糖醛酸基转移酶和谷胱甘肽S - 转移酶分别占肝脏总活性的28.6%和7.4%。该患者可能患有吉尔伯特综合征，其小肠黏膜中相对大量的胆红素UDP - 葡萄糖醛酸基转移酶活性可能表明，在病理条件下肠道代谢可能对胆红素的清除有显著贡献。用单克隆抗体可在微粒体中免疫检测到UDP - 葡萄糖醛酸基转移酶同工型。在肝脏中，可见两条带，一条为57千道尔顿，另一条在53至54千道尔顿之间。在近端小肠中检测到两种同工型（53和54千道尔顿）。然而，在胆红素UDP - 葡萄糖醛酸基转移酶活性较低的远端小肠中，仅可见一种同工型（54千道尔顿）。这可能表明胆红素UDP - 葡萄糖醛酸基转移酶活性与53千道尔顿的同工型相关。本研究进一步证实了人类中存在多种UDP - 葡萄糖醛酸基转移酶同工型，这与之前在大鼠中描述的情况类似。
