The basic kinetic parameters, V and Km, have been determined for liver enzymes involved in the metabolism of fructose and ethanol in rats and man. Values, previously not reported, or which deviate significantly from those reported in the literature are as follows: The maximal activity of aldehyde dehydrogenase from human liver with acetaldehyde as substrate was determined as 43 pmol x min-l x g wet wt-l. The activity of NADP-dependent alcohol dehydrogenase with ethanol as substrate both in rat liver and in human liver was very low. The presence of glycerate kinase (12 pmol x min-l x g wet &-I) in human liver has been established. The K,-value of human-liver alcohol dehydrogenase (NAD) for D-glyceraldehyde was determined as 80-90mM compared to 8-10mM for the rat liver enzyme. The NADP-dependent alcohol dehydrogenase from human liver had a Km-value for D-glyceraldehyde of 2.5-3.3 mM. Glycerate kinase from human and rat liver had K,-values for D-glyceraldehyde of 2.5-3.0 mM and 0.03 mM, respectively.I n slices of human liver the increase in ethanol-oxidation rate caused by 11 mM fructose ('the fructose effect') or by 2 mM D-glyceraldehyde was 76O/, and 56O/,, respectively.I n rat-liver slices the effect of D-glyceraldehyde upon ethanol metabolism was inhibited 1000/o by rotenone. I n the same experiments rotenone caused a 5001, inhibition of the basic ethanol oxidation rate and of the oxygen consumption.10 mM pyruvate, in experiments with liver slices from fasted rats, caused a 9001, increase in the ethanol oxidation rate in the absence of CO,, but only a 200/, increase in the presence of CO,. CO, in itself caused a 700/, increase in the unstimulated oxidation of ethanol.Kinetic considerations and results reported in this paper held together with results from other laboratories lead to the conclusion that the theories previously proposed for the effect of fructose, D-glyceraldehyde or pyruvate upon ethanol metabolism are irreconcilable with the experimental results. A new hypothesis for the 'fructose effect' is proposed.Malate dehydrogenase, malic enzyme, pyruvate carboxylase and transfer of oxaloacetate from the mitochondria1 to the extramitochondrial compartment constitute a mechanism by which transfer of hydrogen from NADH to NADP may take place, thus increasing the rate of removal of NADH from the cytoplasm.I n the liver ethanol is oxidized to acetate via acetaldehyde. The oxidation to acetaldehyde, catalyzed by the cytosolic alcohol dehydrogenase, has been thought to be the rate-limiting step in ethanol metabolism [I]. There is, however, no correlation between the alcohol dehydrogenase activity measured in vitro and the rate of ethanol oxidation in vivo or in liver slices [2,3,4]. As the activity of the enzyme does not appear to be the rate-limiting factor, it is assumed that the oxidation of NADH is ratelimiting for the ethanol oxidation in vivo.During ethanol metabolism acetaldehyde does not accumulate in the liver and is probably oxidized immediately by aldehyde dehydrogenase to acetate [ 5 ] . Thus 2 mol N...

1. Fructose caused an increase in the rate of ethanol oxidation by rat-liver slices, and d-glyceraldehyde was found to have a similar effect. 2. Addition of glycerol lowered the rate of ethanol oxidation if the incubation medium contained fructose and ethanol, but no such effect was found if it contained glucose and ethanol. 3. The formation of glycerol by the slices during incubation and the concentration of alpha-glycerophosphate in the slices were highest in medium containing fructose and ethanol. 4. In experiments without ethanol in the incubation medium, fructose strongly increased the pyruvate concentration, which resulted in a decrease of the lactate/pyruvate concentration ratio. Addition of ethanol to the medium resulted in a marked decrease in pyruvate concentration. 5. Oxygen consumption is greater in slices incubated in medium containing fructose and ethanol than in slices incubated in medium containing glucose and ethanol.

1. Isolated rat-liver parenchymal cells oxidized ethanol a t a rate of 1.4, 1.7, i.9 and 2.5 p.mol/ min per ml packed cells at 4, 20, 40 and 65 mM ethanol, respectively. Between 40 and 65 mM ethanol an abrupt 30°/, increase in the ethanol oxidation rate was observed.2. The activity of the NAD-dependent alcohol dehydrogenase in a homogenate of isolated cells corresponded to 1.25-5 U/ml packed cells, depending on the assay method used.3. Fructose or pyruvate enhanced the oxidation rate of ethanol by 1.4-2.0 pmol/min per ml packed cells independent of the ethanol concentration applied. No additive effect of the two compounds upon ethanol oxidation was observed.4. Pyrazole inhibited the NAD dependent alcohol dehydrogenase activity in a homogenate of isolated cells as well as the unstimulated and the fructose-stimulated ethanol oxidation with a Ki-value of 9-13 pM.by pyrazole concentrations, which inhibited the unstimulated ethanol oxidation only 30 Ole, indicating that the "fructose effect" is mediated via alcohol deh y drogenase .4mM pyrazole only slightly inhibited that part of the ethanol oxidation which was not catalyzed by alcohol dehydrogenase, whereas 18 mM pyrazole inhibited also this pathway significantly. 5. 50 pM pyrazole had no effect a t all upon the basal ethanol oxidation rate whereas the fructose-stimulated ethanol oxidation was 30°/, inhibited.6. The results concerning the effect of fructose and pyruvate upon ethanol oxidation are interpreted in terms of the mechanism for the reaction catalyzed by alcohol dehydrogenase. At low concentrations of ethanol and in the absence of fructose, the rate-limiting step in ethanol oxidation appears to be dissociation of the enzyme-NADH complex, whereas, in the presence of fructose, the maximal activity of ethanol dehydrogenase may be rate-limiting for the oxidation of ethanol.7. The results also suggest that enzyme systems other than alcohol dehydrogenase participate in ethanol oxidation a t high concentrations of ethanol.The "fructose effect" was inhibited 100Three different reaction mechanisms for oxidation of ethanol to acetaldehyde have been described in liver tissue. These are the pathway catalyzed by the NAD-dependent alcohol dehydrogenase [ 11, the pathway involving hydrogen peroxide and catalase [2 -51 and the microsomal ethanol-oxidizing system involving NADPH and cytochrome P-450 [6-81. The pathway catalyzed by alcohol dehydrogenase is localized to the cytoplasmic compartment of the cell, while the system dependent on cytochrome P-450 is microsome-bound. Eur. J. Bioohem. 40 (1973) The oxidation of ethanol catalyzed by alcohol dehydrogenase, which prevails a t low (below approx.

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Dich, J., S. E. Hansen and H. I. D. Thieden. Effect of albumin concentration and colloid osmotic pressure on albumin synthesis in the perfused rat liver. Acta physiol. scand. 1973. 89. 352–358. The effect of the albumin concentration and the colloid osmotic pressure on the rate of albumin synthesis was investigated in the perfused rat liver. The albumin concentration and the colloid osmotic pressure were changed independently. With the same concentration of albumin the rate of albumin synthesis decreased 20 to 30 per cent when the colloid osmotic pressure was increased by addition of gammaglobulin. It is concluded that the rate of albumin synthesis may be regulated by the colloid osmotic pressure. The albumin concentration seems to play a role in regulation only through the contribution to the colloid osmotic pressure.