Illing H P, Benford D
Biochim Biophys Acta. 1976 May 13;429(3):768-79. doi: 10.1016/0005-2744(76)90324-7.
The partition coefficients between octanol and pH 7.4 buffer for eleven substrates of UDP-glucuronosyltransferase (EC 2.4.1.17) have been determined. They range between 1.1 and 690 in the order p-aminophenol less than phenol less than (o-aminobenzoic acid = o-aminophenol = p-aminobenzoic acid) less than p-nitrophenol less than 4-methylumbelliferone less than mercaptobenzothiazole less than harmol less than phenolphthalein less than 1-naphthol. The effect of Triton X-100, used as a model membrane pertubant, on the enzyme activity of UDP-glucuronosyltransferase in rat liver homogenates towards these substrates was determined and compared with the partition coefficients. Enzyme activities towards p-aminophenol and phenol were decreased by Triton X-100, the enzyme activities towards other acceptor substrates were enhanced maximally with 0.025% (w/v) Triton. "Native" enzyme activity (except for amino containing compounds) and activation could be related to partition coefficient of the substrate. An increase in lipid solubility resulted in reduced enzyme activity in untreated homogenates and greater activation. These results suggest UDP-glucuronosyltransferase lies behind a partially lipid-impenetrable abrrier and it is suggested that this barrier is broken up by membrane perturbants to permit free access of the more lipid-soluble substrates. In addition, the formation in vitro of a glucuronide from mercaptobenzothiazole was demonstrated.
已测定了UDP-葡萄糖醛酸基转移酶（EC 2.4.1.17）的11种底物在正辛醇与pH 7.4缓冲液之间的分配系数。它们的范围在1.1至690之间，顺序为对氨基苯酚＜苯酚＜（邻氨基苯甲酸 = 邻氨基酚 = 对氨基苯甲酸）＜对硝基苯酚＜4-甲基伞形酮＜巯基苯并噻唑＜哈尔满＜酚酞＜1-萘酚。测定了用作模型膜扰动剂的吐温X-100对大鼠肝匀浆中UDP-葡萄糖醛酸基转移酶针对这些底物的酶活性的影响，并与分配系数进行了比较。吐温X-100降低了针对对氨基苯酚和苯酚的酶活性，而针对其他受体底物的酶活性在0.025%（w/v）吐温时最大程度增强。“天然”酶活性（含氨基化合物除外）和激活作用可能与底物的分配系数有关。脂质溶解度的增加导致未处理匀浆中的酶活性降低以及更大程度的激活。这些结果表明UDP-葡萄糖醛酸基转移酶位于部分脂质不可渗透的屏障之后，并且表明该屏障被膜扰动剂打破，以允许更具脂溶性的底物自由进入。此外，还证实了巯基苯并噻唑在体外形成葡萄糖醛酸苷。
