Krcmery M, Zakim D
Division of Digestive Diseases, Cornell University Medical College, New York, NY 10021.
Biochem Pharmacol. 1993 Sep 1;46(5):897-904. doi: 10.1016/0006-2952(93)90500-v.
Addition of oleoyl-CoA to microsomes inhibited UDP-glucuronosyltransferase (assayed with 1-naphthol or p-nitrophenol) at concentrations within the physiologic range of total long-chain acyl-CoAs in liver. Inhibition of activity was associated with changes in the regulatory properties of the enzyme indicating that oleoyl-CoA altered the functional state of UDP-glucuronosyltransferase. The effect of oleoyl-CoA on the state of UDP-glucuronosyltransferase depended on the concentration of oleoyl-CoA, whether oleoyl-CoA was added in the presence or absence of substrates, the duration of treatment with oleoyl-CoA, and the aglycone with which activity was assayed. When oleoyl-CoA was added to microsomes in the presence of aglycones or UDP-glucuronic acid, inhibition by oleoyl-CoA was reversed by albumin, which by itself had no effect on activity. But UDP-glucuronosyltransferase, assayed with either aglycone, did not revert to the native state on removing oleoyl-CoA. Instead sequential treatment with oleoyl-CoA and albumin, in the presence of at least one substrate, produced a form of UDP-glucuronosyltransferase that was more active than the native state. When oleoyl-CoA was added to microsomes in the absence of aglycones or UDP-glucuronic acid, the activity of enzymes assayed with 1-naphthol decayed irreversibly to zero. Similar treatment followed by assay with p-nitrophenol as aglycone led to an active form of the enzyme that was inhibited further by albumin. The data are compatible with the idea that long-chain acyl-CoAs could regulate the functional state of UDP-glucuronosyltransferase.
在肝脏中，将油酰辅酶A添加到微粒体中，在总长链酰基辅酶A的生理浓度范围内，会抑制UDP-葡萄糖醛酸基转移酶（用1-萘酚或对硝基苯酚测定）。活性的抑制与酶调节特性的变化有关，表明油酰辅酶A改变了UDP-葡萄糖醛酸基转移酶的功能状态。油酰辅酶A对UDP-葡萄糖醛酸基转移酶状态的影响取决于油酰辅酶A的浓度、油酰辅酶A是否在有或无底物的情况下添加、油酰辅酶A处理的持续时间以及用于测定活性的糖苷配基。当在糖苷配基或UDP-葡萄糖醛酸存在的情况下将油酰辅酶A添加到微粒体中时，白蛋白可逆转油酰辅酶A的抑制作用，而白蛋白本身对活性无影响。但是，用任何一种糖苷配基测定的UDP-葡萄糖醛酸基转移酶在去除油酰辅酶A后不会恢复到天然状态。相反，在至少一种底物存在的情况下，依次用油酰辅酶A和白蛋白处理会产生一种比天然状态更具活性的UDP-葡萄糖醛酸基转移酶形式。当在没有糖苷配基或UDP-葡萄糖醛酸的情况下将油酰辅酶A添加到微粒体中时，用1-萘酚测定的酶活性不可逆地衰减至零。以对硝基苯酚作为糖苷配基进行类似处理并测定，会导致酶呈现一种活性形式，该形式会被白蛋白进一步抑制。这些数据与长链酰基辅酶A可以调节UDP-葡萄糖醛酸基转移酶功能状态的观点一致。
