Aw T Y, Jones D P
Chem Biol Interact. 1983 Mar;43(3):283-8. doi: 10.1016/0009-2797(83)90112-6.
The enzymatic basis for inhibition of drug glucuronidation during ethanol oxidation was investigated in isolated rat hepatocytes. The intracellular rate of glucuronidation was varied independently by controlling the steady-state O2 concentration and the concentrations of UDP-glucose and UDP-glucuronic acid were measured in the absence and presence of 20 mM ethanol. Ethanol caused substantial inhibition of the glucuronidation rate which corresponded to a significant decrease in UDP-glucuronic acid concentration but not in UDP-glucose concentration. A plot of glucuronidation rate as a function of cellular UDP-glucuronic acid concentration yielded a single curve for incubations with or without ethanol; a similar plot of glucuronidation against UDP-glucose concentration gave separate curves for the two incubation conditions. These results clearly define the UDP-glucose dehydrogenase reaction as the site of inhibition during ethanol oxidation.
在分离的大鼠肝细胞中研究了乙醇氧化过程中药物葡萄糖醛酸化抑制的酶学基础。通过控制稳态氧浓度独立改变细胞内葡萄糖醛酸化速率，并在不存在和存在20 mM乙醇的情况下测量UDP-葡萄糖和UDP-葡萄糖醛酸的浓度。乙醇导致葡萄糖醛酸化速率大幅抑制，这对应于UDP-葡萄糖醛酸浓度显著降低，但UDP-葡萄糖浓度未降低。以葡萄糖醛酸化速率作为细胞UDP-葡萄糖醛酸浓度的函数作图，无论有无乙醇孵育均得到一条单一曲线；以葡萄糖醛酸化相对于UDP-葡萄糖浓度作图，在两种孵育条件下得到不同的曲线。这些结果清楚地确定UDP-葡萄糖脱氢酶反应是乙醇氧化过程中的抑制位点。
