EFFECTS OF ALIPHATIC ALCOHOLS ON THE METABOLISM OF GLUCOSE AND FRUCTOSE IN RAT LIVER SLICES

Abstract

Ethanol, at concentrations up to 3 mM, whilst having little inhibitory effect on the production of respiratory CO₂of rat liver slices, has a marked suppressing action on the formation of labelled CO₂from labelled glucose. The suppression of C¹⁴O₂formation by ethanol from radioactive glucose is independent of the concentration of the latter and amounts to 57% with 3 mM ethanol after 1 hour's incubation. The results are consistent with the conclusion that ethanol gives rise more rapidly than glucose to acetyl CoA and that the large suppressing action of ethanol in rat liver slices is due to isotopic dilution of labelled acetyl CoA derived from the labelled sugars with the unlabelled acetyl CoA derived from ethanol. Ethanol exercises a larger inhibition of the rate of C¹⁴O₂formation from glucose-6-C¹⁴than from glucose-1-C¹⁴. The difference between the effects of ethanol on C¹⁴O₂formation from glucose-1-C¹⁴and glucose-6-C¹⁴is presumably due to operation of the hexosemonophosphate shunt.The higher aliphatic alcohols have about the same diminishing effect on C¹⁴O₂formation from glucose-U-C¹⁴and fructose-U-C¹⁴as does ethanol. This observation may also be a consequence of dilution of labelled acetyl CoA derived from the sugars by unlabelled acetyl CoA coming from the added alcohol. Incorporation of radioactive carbon from the labelled sugars into liver proteins and lipids is inhibited by ethanol and higher aliphatic alcohols, and the inhibitions are similar in magnitude to those of C¹⁴O₂formation. These may be accounted for by isotopic dilution. The amounts of C¹⁴incorporated into lipids and proteins from radioactive glucose and fructose are small, being about 1/10th of that appearing in the CO₂.The higher aliphatic alcohols suppress total CO₂formation during rat liver slice respiration much more than does ethanol at equivalent concentrations.