UDP-GLUCURONYLTRANSFERASES

葡萄糖醛酸偶联是药物代谢的主要途径，为药物代谢提供了新的途径。 具有消除脂溶化学物质的方法的活的有机体 他们暴露在危险之中。肝微粒体UDP-葡萄糖醛酸基转移酶 催化葡萄糖醛酸苷的形成。我们实验室已经分离出一种 这些蛋白质的数量在接合过程中起重要作用 外源物质和内源物质。 肝小叶定位及分布的测定 对硝基苯酚UDP-葡萄糖醛酸基转移酶(PNP-UDPGT)，17β-羟基类固醇 UDPGT和3Alpha-OH类固醇UDPGT的免疫组织化学分析 有计划的。使用特定的抗体，研究将证明这些变化 在分布中由各种试剂产生，如3-甲基胆蒽。 此外，还将研究肝脏、胃肠道、肺和肾脏。 来自Wistar大鼠，具有高水平的3Alpha-OH类固醇UDPGT(HA)和 低水平的3Alpha-OH类固醇UDPGT(LA)。这些研究将允许 了解细胞异质性在葡萄糖醛酸化反应中的作用。 实验将揭示PNP-UDPGT的N末端氨基酸序列， 17β-羟基类固醇UDPGT和3Alpha-OH类固醇UDPGT。此外， 这些转移酶在未治疗大鼠体内表达的遗传调控 用3-甲基胆蒽处理的大鼠的肝脏和肝脏中 学习。3Alpha-OH类固醇UDPGT的遗传变异机制 将在HA和LA Wistar大鼠身上进行研究。吗啡的提纯及精制 将进行洋地黄素单洋地黄苷UDPGTS，然后，这些 将对酶进行进一步研究，如对其他UDPGT所述。 将进行人肝UDPGTS的纯化和鉴定。 磷脂需要量、N端氨基酸序列的实验 人肝组织UDPGT基因表达的遗传调控 有计划的。最后，细胞异质性在人体组织中的作用将 用免疫组织化学方法进行检测。因此，如何以及在哪里 葡萄糖醛酸化作用的发生是可以探测和理解的。

Glucuronide conjugation is a major route of drug metabolism and provides living organisms with a way to eliminate lipid-soluble chemicals to which they are exposed. Hepatic microsomal UDP-glucuronyltransferases (UDPGTs) catalyze the formation of glucuronides. Our laboratory has isolated a number of these proteins which are important in the conjugation of xenobiotics and endogenous substances. Determination of hepatic lobular localization and distribution of p-nitrophenol UDP-glucuronyltransferase (PNP-UDPGT), 17Beta-OH steroid UDPGT and 3Alpha-OH steroid UDPGT by immunohistochemical analyses is planned. Using specific antibodies, studies will demonstrate the changes in distribution produced by various agents such as 3-methylcholanthrene. In addition, liver, gastrointestinal tract, lung and kidney will be studied from Wistar rats possessing high levels of 3Alpha-OH steroid UDPGT (HA) and low levels of 3Alpha-OH steroid UDPGT (LA). These studies will allow for an understanding of the role of cellular heterogeneity in glucuronidation. Experiments will reveal N-terminal amino acid sequences of PNP-UDPGT, 17Beta-OH steroid UDPGT and 3Alpha-OH steroid UDPGT. In addition, the genetic regulation of expression of these transferases in untreated rat livers and in livers of rats treated with 3-methylcholanthrene will be studied. The mechanism of genetic variance for 3Alpha-OH steroid UDPGT will be studied in HA and LA Wistar rats. Purification of morphine and digitoxigenin monodigitoxoside UDPGTs will be performed and, then, these enzymes will be studied further as described for other UDPGTs. Purification and characterization of human liver UDPGTs will be performed. Experiments on phospholipid requirements, N-terminal amino acid sequences and the genetic regulation of expression of human liver UDPGTs are planned. Finally, the role of cellular heterogeneity in human tissues will be explored using immunohistochemical methods. Thus, how and where glucuronidation occurs can be probed and understood.