Metabolism of Ethanol and Fructose in the Isolated Perfused Pig Liver

Abstract

1. Ethanol at concentrations below 10 mM was oxidized a t a rate of 0.7 pmol x g-1 x 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 a t 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 1000/, by fructose in the presence of ethanol. 4.The concentration ratios of sorbitol/fructose and lactatelpyruvate 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 pmol 0, x g-1 x min-l compared to a measured uptake of 1.8 pmol x g-l x 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.

The Stimulatory Effect of Fructose on Ethanol Metabolism

“…By this mechanism the dissociation of the reduced coenzyme from the apoenzyme which was shown to be the rate-limiting step in the overall reaction of isolated alcohol dehydrogenase (29,30) would be circum vented. However, since the Km for glyceraldehyde for alcohol dehydrogenase is high (13), a sufficient oxidation rate via this mechanism would require intracel lular concentrations of glyeraldehyde at least one order of magnitude higher than those observed in liver tissue in the presence of fructose (17). In fact, the release of glycerol from the liver is small indicating that a removal of reducing equivalents via the reduction of glyceraldehyde accounts for less than 10% of the stimulatory effect of fructose on ethanol metabolism (table II).…”

“…However, during fructose metabolism, sorbitol or other polyalcohols are released from the liver at very low rates, even in the presence of ethanol (17,31), probably due to the low affinity of sorbit dehydrogenase for fructose (17,32).…”

The Metabolism of Acetate in the Perfused Hind‐Quarter of the Rat

“…During hepatic ethanol oxidation acetate is formed stoichiometrically (Lundquist et af. 1962) and 70-80% of the oxidized ethanol appears as free acetate in the hepatic venous outflow a, Damgaard et al 1973). Due to the further rapid oxidation of acetate in extrahepatic tissues (Lundquist et al 1962, Forsander et a/.…”

Another 'soberade' on the market: does Outox keep its promise?

“…Fructose is metabolized to fructose-1-phosphate and then to D-glyceraldehyde, so it was assumed that in the presence of ethanol further metabolism to glycerol takes place, needing NADH and therefore providing NAD+, instead of the usual metabolism to glycerate [13]. In fact it was shown that in the presence of ethanol the output of glycerate was completely suppressed [6]. However, it was doubted that this mechanism alone is a sufficient explanation, and further metabolism of glycerate to pyruvate and oxaloacetate was proposed, followed by the NADH2-requiring metabolism of oxaloacetate to malate [14].…”

“…The ability of fructose to decrease ethanol levels was first demonstrated [4] and then confirmed in several studies, e.g. [5][6][7]. The mechanism of this so called 'fructose effect' was thoroughly investigated but led to partly different conclusions.…”