Predominance of glycolysis in pericentral regions of the liver lobule.
Predominance of glycolysis in pericentral regions of the liver lobule.
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糖酵解主要发生在肝小叶的中央周围区域。
DOI：
10.1111/j.1432-1033.1984.tb08091.x
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Thurman,RG
中科院分区：
文献类型：
--
作者：
Matsumura,T;Thurman,RG
1喂食大鼠灌注的肝脏输注2 mM乙醇可增加摄氧量，同时糖酵解（乳酸+丙酮酸生成）速率降低。摄氧量的增加与整个器官乳酸+丙酮酸生成速率的降低之间存在线性相关（r= 0.92），这是由进水浓度与流出浓度之间的差异决定的。然后将微型氧电极（针尖直径50 μm）放置在肝表面的门静脉周围或小叶中心周围区域，通过停止灌注液的流动和监测氧浓度的下降速度来确定局部的摄氧率（“停止流摄氧技术”）。在顺行灌注过程中，乙醇（2 mM）对大鼠肝小叶中心周围（15 μmol × g−1× h−1）的摄氧率比门静脉周围（7 μmol × g−1× h−1）的摄氧率高约两倍。相反，在禁食大鼠的肝脏中，乙醇没有显著影响肝小叶两个区域的摄氧量。3葡萄糖（30mm）顺行灌注入禁食大鼠肝脏后，可降低肝小叶两个区域的氧浓度。随后，葡萄糖增加了肝小叶中央周围而不是门静脉周围的氧浓度。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）。在葡萄糖存在的情况下，乙醇的加入降低了乳酸+丙酮酸的生成速率，并增加了主要在中心周围区域的吸氧速率。这些数据与以下解释一致。乙醇代谢提高肝小叶门静脉周围和中心周围区域的NADH，引起甘油醛- 3 -磷酸脱氢酶的氧化还原抑制和糖酵解ATP合成速率的降低。在细胞质中未磷酸化的ADP随后进入线粒体并刺激氧气的摄取。由于乙醇和葡萄糖在更大程度上提高了肝小叶中央周围区域的摄氧量，因此我们得出结论，在顺行方向灌注时，糖酵解主要发生在位于中心静脉近端的肝细胞中。5当逆行灌注进行类似实验时，糖酵解局限于肝小叶的门静脉周围区域。因此，在灌注的肝脏中，碳水化合物代谢的代谢区带可以在肝小叶区域内迅速转移。
1Infusion 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.2Miniature oxygen electrodes (tip diameter, 50 μm) 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 μmol × g−1× h−1) than in periportal (7 μmol × g−1× 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.3Glucose (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.4These 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.5When similar experiments were performed with perfusion in the retrograde direction, glycolysis was localized in periportal regions of the liver lobule. Thus, metabolic zonation of carbohydrate metabolism can be shifted rapidly within regions of the liver lobule in perfused liver.