Matsumura T, Thurman R G
Eur J Biochem. 1984 Apr 16;140(2):229-34. doi: 10.1111/j.1432-1033.1984.tb08091.x.
Infusion of 2 mM ethanol into perfused liver from fed rats increased the rate of oxygen uptake concomitant with the decrease in the rate of glycolysis (lactate + pyruvate production). A linear correlation (r = 0.92) was observed between the increase in the rate of oxygen uptake and the decrease in the rate of lactate + pyruvate production determined on the whole organ by the difference between influent minus effluent concentration. Miniature oxygen electrodes (tip diameter, 50 micron) were then placed on periportal or pericentral regions of the lobule on the liver surface, and local rates of oxygen uptake were determined by stopping the flow of perfusate and monitoring the rate of decrease of oxygen concentration ('stopped-flow oxygen uptake technique'). During perfusion in the anterograde direction, ethanol infusion (2 mM) increased rates of oxygen uptake about twofold more in pericentral (15 mumol X g-1 X h-1) than in periportal (7 mumol X g-1 X h-1) regions of the liver lobule in livers from well-fed rats. In contrast, ethanol did not affect the rate of oxygen uptake significantly in either region of the liver lobule in livers from fasted rats. Glucose (30 mM) decreased oxygen concentrations initially in both regions of the liver lobule when infused into livers from fasted rats perfused in the anterograde direction. Subsequently, glucose increased the oxygen concentration in pericentral but not periportal regions of the liver lobule. This increase in regional oxygen concentration correlated temporally (r = 0.99) with increases in rates of glycolysis. The addition of ethanol in the presence of glucose reduced the rate of lactate + pyruvate production and increased the rate of oxygen uptake predominantly in pericentral regions. These data are consistent with the following interpretation. Ethanol metabolism elevates NADH in both periportal and pericentral regions of the liver lobule causing redox inhibition of glyceraldehyde-3-phosphate dehydrogenase and decreased rates of glycolytic ATP synthesis. The ADP not phosphorylated in the cytosol then moves into the mitochondrion and stimulates oxygen uptake. Since ethanol and glucose elevated oxygen uptake to a greater extent in pericentral regions of the liver lobule, it is concluded that glycolysis predominates in hepatocytes located proximal to the central vein during perfusion in the anterograde direction. When similar experiments were performed with perfusion in the retrograde direction, glycolysis was localized in periportal regions of the liver lobule.(ABSTRACT TRUNCATED AT 400 WORDS)
向喂食大鼠的灌注肝脏中输注2 mM乙醇，会增加氧摄取速率，同时糖酵解速率（乳酸 + 丙酮酸生成速率）降低。通过流入液减去流出液浓度的差值在整个器官上测定，观察到氧摄取速率的增加与乳酸 + 丙酮酸生成速率的降低之间存在线性相关性（r = 0.92）。然后将微型氧电极（尖端直径50微米）放置在肝脏表面小叶的门静脉周围或中央静脉周围区域，通过停止灌注液流动并监测氧浓度降低速率（“停流氧摄取技术”）来测定局部氧摄取速率。在顺行灌注期间，对于喂食良好的大鼠肝脏，输注乙醇（2 mM）使肝脏小叶中央静脉周围区域（15 μmol·g⁻¹·h⁻¹）的氧摄取速率增加幅度比门静脉周围区域（7 μmol·g⁻¹·h⁻¹）大约两倍。相比之下，乙醇对禁食大鼠肝脏小叶的两个区域的氧摄取速率均无显著影响。当向顺行灌注的禁食大鼠肝脏中输注葡萄糖（30 mM）时，最初在肝脏小叶的两个区域均降低了氧浓度。随后，葡萄糖增加了肝脏小叶中央静脉周围区域而非门静脉周围区域的氧浓度。这种区域氧浓度的增加与糖酵解速率的增加在时间上相关（r = 0.99）。在有葡萄糖存在的情况下添加乙醇会降低乳酸 + 丙酮酸生成速率，并主要增加中央静脉周围区域的氧摄取速率。这些数据与以下解释一致。乙醇代谢会升高肝脏小叶门静脉周围和中央静脉周围区域的NADH，导致甘油醛 - 3 - 磷酸脱氢酶的氧化还原抑制以及糖酵解ATP合成速率降低。然后，胞质溶胶中未磷酸化的ADP进入线粒体并刺激氧摄取。由于乙醇和葡萄糖在肝脏小叶中央静脉周围区域更大程度地提高了氧摄取速率，得出结论：在顺行灌注期间，位于中央静脉近端的肝细胞中糖酵解占主导。当以逆行灌注进行类似实验时，糖酵解位于肝脏小叶的门静脉周围区域。（摘要截短于400字）
