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利用肝脏灌流模型及肝脏微粒体对油酸影响羟基苯并[a]芘葡萄糖醛酸化的机理进行了研究,结果表明,低剂量的油酰辅酶A可非竞争性地抑制大鼠肝微粒体UDP-葡萄醛酰转移酶的活性,使3-羟基苯并芘葡萄糖醛酰化作用受抑制,牛血清白蛋白与Triton X-100可促进油酰辅酶A对转移酶的抑制作用。 600 μmol·L~(-1)的油酸灌流肝脏,可使肝脏中UDPGA,UDPG及ATP分别下降44％,49％及44％,因此高剂量的油酸亦可通过改变辅因子供应而抑制羟基苯并芘的葡萄糖醛酸化过程。 250μmol·L~(-1)的油酸灌流缺乏β-葡萄糖醛酸酶的C_3H/He小鼠肝脏,可使流出液中游离羟基苯并芘增加136％,而与葡萄糖醛酸结合的羟基苯并芘减少了32％,同时肝脏中与葡萄糖醛酸结合的羟基苯并芘减少64％,以油酸灌流具有高β-葡萄糖醛酸酶的DBA/2小鼠肝脏可见同样改变,在肝脏微粒体的实验中亦未见油酰辅酶A对苯并芘-0-葡萄糖醛酸的水解作用有何影响,据此,油酸对羟基苯并芘葡萄醛酸化状态的影响与β-葡萄糖醛酸酶无关。
Liver perfusion model and liver microsomes were used to study the mechanism of oleic acid affecting glucuronidation of hydroxybenzo [a] pyrene. The results showed that low dose oleoyl coenzyme A could non-competitively inhibit rat liver microsomal UDP - glucuronosyltransferase activity, inhibition of 3-hydroxybenzopyrene glucuronidation, bovine serum albumin and Triton X-100 can promote oleoyl-CoA transferase inhibition. Perfusion of liver with 600 μmol·L -1 oleic acid reduced the levels of UDPGA, UDPG and ATP in the liver by 44%, 49% and 44%, respectively. Therefore, high doses of oleic acid could also be suppressed by changing the cofactor supply Hydroxybenzopyrene glucuronidation process. 250μmol·L -1 oleic acid perfused the liver of C_3H / He mice lacking β-glucuronidase, which increased the free hydroxybenzopyrene by 136% in the effluent, whereas the hydroxybenzene bound to glucuronide And pyrene decreased by 32%, while glucuronic acid in the liver combined with hydroxybenzaprene decreased by 64%, with oleic acid perfusion of DBA / 2 mice with high β-glucuronidase can be seen the same change in the liver particles In vivo experiments showed no effect of oleoyl-CoA on the hydrolysis of benzopyrene-0-glucuronic acid. Therefore, the effect of oleic acid on the state of hydroxybenzopyrene glucuronidation was related to the effect of β-glucuronic acid Has nothing to do with enzymes.