Lane S E, Stewart M E
Biochim Biophys Acta. 1983 Feb 22;755(3):313-7. doi: 10.1016/0304-4165(83)90232-5.
Interaction of alcohol and drugs in the liver appears to involve common microsomal oxidative enzymes which utilize cytochrome P-450. Since alcohol augments the toxicity of a variety of drugs, the regulation of the P-450 hemoprotein, a primary component in hepatic drug metabolizing systems, may play a vital role in this phenomenon. We utilize an adult rat liver culture system as a model to explore the action of levels of alcohol below that which is necessary to produce intoxication in humans. The addition of 16 mM ethanol (70 mg/dl) to these hepatocytes results in a 49.5% decrease in cytochrome P-450 activity after 24 h, and a 3-fold increase in the activity of delta-aminolevulinate synthase, the rate-limiting enzyme in hepatic heme biosynthesis. Furthermore, ethanol treatment also causes a transient decrease in the level of intracellular heme. However, the diminished level of total heme does not appear to act as a repressor for delta-aminolevulinate synthase, since it occurs after the initial stimulation of the enzyme by ethanol.
酒精与药物在肝脏中的相互作用似乎涉及共同的微粒体氧化酶，这些酶利用细胞色素P - 450。由于酒精会增强多种药物的毒性，P - 450血红蛋白（肝脏药物代谢系统的主要成分）的调节可能在这一现象中起关键作用。我们利用成年大鼠肝脏培养系统作为模型，来探究低于人类中毒所需剂量的酒精水平的作用。向这些肝细胞中添加16 mM乙醇（70 mg/dl），24小时后细胞色素P - 450活性降低49.5%，而肝脏血红素生物合成中的限速酶δ-氨基乙酰丙酸合酶的活性增加了3倍。此外，乙醇处理还会导致细胞内血红素水平短暂下降。然而，总血红素水平的降低似乎并未作为δ-氨基乙酰丙酸合酶的抑制剂起作用，因为它发生在乙醇对该酶的初始刺激之后。
