Predominance of glycolysis in pericentral regions of the liver lobule

Abstract

Infusion of 2 mM ethanol into perfused liver from fed rats increased the rate of O2 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 O2 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 O2 electrodes (tip diameter, 50 .mu.m) were than placed on periportal or pericentral regions of the lobule on the liver surface, and local rates of O2 uptake were determined by stopping the flow of perfusate and monitoring the rate of decrease of O2 concentration (stopped-flow O2 uptake technique). During perfusion in the anterograde direction, ethanol infusion (2 mM) increased rates of O2 uptake .apprx. 2-fold more in pericentral (15 .mu.mol .times. g-1 .times. h-1) than in periportal (7 .mu.mol .times. g-1 .times. h-1) regions of the liver lobule in livers from well-fed rats. In contrast, ethanol did not affect the rate of O2 uptake significantly in either region of the liver lobule in livers from fasted rats. Glucose (30 mM) decreased O2 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 O2 concentration in pericentral but not periportal regions of the liver lobule. This increase in regional O2 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 O2 uptake predominantly in pericentral regions. These data are consistent with the following interpretation. Ethanol metabolism elevates NADH in both periporal 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 O2 uptake. Since ethanol and glucose elevated O2 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. Thus, metabolic zonation of carbohydrate metabolism can be shifted rapidly within regions of the liver lobule in perfused liver.