Metabolism of Ethanol and Fructose in the Isolated Perfused Pig Liver

1 Ethanol at concentrations below 10 mM was oxidized at a rate of 0.7 μmol×g−1× min−l by the perfused pig liver. Infusion of fructose caused a stimulation (up to 120%) of ethanol oxidation, which was proportional to the rate of fructose elimination. 2 Stimulation was observed also when d‐glyceraldehyde (a fructose metabolite) was used. Even at high d‐glyceraldehyde concentrations, the increase in ethanol metabolism was less than with fructose. 3 Hepatic acetate metabolism was not affected by ethanol but was stimulated up to 100% by fructose in the presence of ethanol. 4 The concentration ratios of sorbitol/fructose and lactate/pyruvate in the perfusion medium were increased in experimental periods with ethanol and fructose compared to periods with fructose alone. The data indicate equilibrium between these metabolites and the free NADH/NAD in the cytosol. 5 The steady‐state concentrations of D‐glyceraldehyde and glycerol were increased when ethanol was infused together with fructose, while the production of d‐glycerate was reduced to zero. 6 The rate of fructose elimination was not influenced by ethanol, although the output of lactate and glucose were diminished. 7 Accumulation of the reduced metabolites (sorbitol, glycerol, l‐glycerol 3‐phosphate) accounted for only a small part of the reducing equivalents generated during fructose‐stimulated ethanol oxidation. Complete oxidation of the ethanol metabolized would require 3.6 μmol O2×g−1×min−l compared to a measured uptake of 1.8 μmol× g−l×min−1. As ketone bodies and acetaldehyde were not produced in significant amounts, the retained acetate must be used in syntheses, e.g. of fatty acids. 8 The experimental results are interpreted in terms of a model, the malate shuttle. Data from experiments with pyrazole and dinitrophenol support the interpretation.