Ethanol-1-C14 and Acetate-1-C14 Incorporation into Lipid Fractions in the Mouse

Abstract

There is general agreement that the metabolism of ethyl alcohol proceeds through acetaldehyde to enter the acetate pool. From this point there is participation in all reactions involving the remaining 2-carbon fragment, such as fatty acid and cholesterol synthesis and oxidation via the tri-carboxylic acid cycle. Schulman et aL(1) have found that the protein, glycogen, fatty acids and cholesterol from rats given a single dose of radioactive alcohol contained 2 to 3 times the labelled carbon in these same constituents from rats receiving CI4 labelled acetate. iVhen report appeared, we had begun similar experiments though of somewhat different design. Since our results differed somewhat from those of Schulman, we considered it worthwhile to pursue our studies further. b T e found that tissue fatty acids, non-saponifiable fraction, and phospholipids take up almost equal amounts of after either radioactive alcohol or acetate administration.Methods. In one set of experiments, pairs of male C-57 B mice were matched in body weight and placed in separate cages where drinking water contained approximately one pc /ml of ethanol-1 -C14 or of acetate-1 -C1-'. When solutions prepared from commercially available ethanol-l-CI4 and a~e t a t e -1 -C~~ were not of equal activity, as determined by Packard Tri-Carb scintillation counter, appropriate dilutions were made until the same activity level was measured in each. Non-radioactive acetate or ethanol was added so that final concentration of additives was 0.2 It. The animals could not tolerate a higher concentration of acetate without loss of weight. T o ethanol-water solution was also added 0.2 11 NaC1 to match the sodium concentration in the acetate solution as closely as possible. Mice remained on this regime with ad lib. feeding of Purina Rat Chow for 5 days, then, 12 hours before au- *Deceased Sept. 19, 19.59. topsy, the remaining water containing radioactive constituents was measured and replaced by fresh water. This time delay before autopsy was chosen to allow complete incorporation of imbibed alcohol and acetate into the tissues. IVhen different amounts of water were drunk by the 2 mice, appropriate correction factor was applied to final result. Tn other experiments, radioactive solutions prepared in same manner as drinking water were injected in amounts of one ml, 3 times daily. These mice were provided with fresh drinking water and laboratory chow ad lib.

Ethanol Metabolism and Production of Free Acetate in the Human Liver

“…Such processes undoubtedly do take place, and equally well from ethanol and acetate (22,23), but to a very minor degree, which can at most explain a small fraction of the acetate deficit in some of the experiments (24), if results obtained in animals are accepted as valid in man. It is therefore considered most probable that all of the ethanol is oxidized to free acetate in the liver, and that the reason for the low recovery of acetate in the hepatic venous blood in some experiments is mainly oxidation in the extrahepatic splanchnic area.…”

Biodistribution of Radiolabeled Ethanol in Rodents

“…After oxidization of ethanol to acetaldehyde, the acetaldehyde is oxidized further to acetate by aldehyde dehydrogenase. The acetate may then enter the tricarboxylate cycle (Isselbacher and Greenberger, 1964a,b) or the long-chain fatty acid synthesis pathway (Hakkinen and Kulonen, 1959;Smith and Newman, 1960). Carbon atoms from labeled acetate are ultimately oxidized to carbon dioxide by the tricarboxylate cycle but are also incorporated into other compounds, including the amino acids glutamate and aspartate, that are metabolically connected to cycle intermediates.…”