THE DIRECT ACTION OF CCl4ON THE METABOLISM OF LIVER SLICES

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Abstract
The metabolism of glucose, galactose, leucine, acetate, and palmitate by rat liver slices incubated in the presence of varying amounts of CCl4was studied. Carbon tetrachloride, 1 to 9 μl, introduced into the side arm of a Warburg vessel, produced concentrations in the slices of 0.4 to 3.3 mg/g liver. At these concentrations the CCl4produced a decrease in C14O2production from succinate-2,3-C14and glucose-6-C14, but not from glucose-1-C14. The presence of CCl4did not appreciably affect CO2production from glucose-U-C14or galactose-1-C14but stimulated the incorporation of the monosaccharides into glycogen at the lower concentrations (1 mg CCl4/g liver). Higher concentrations of CCl4(2 mg/g liver) inhibited glycogen synthesis; the activities of glycogen synthetase and phosphorylase were decreased, but amylase activity and the level of glucose-6-phosphate in the liver slices remained unchanged. The oxidation of palmitate-1-C14and acetate-1-C14to C14O2is decreased at the higher concentrations of CCl4, while lipogenesis from acetate is stimulated by lower concentrations of CCl4. Esterification of palmitate is not affected by the presence of CCl4. It is concluded that the function of the tricarboxylic acid cycle is altered by CCl4and that acetate may be shunted into fatty acids. The oxidation of leucine-1-C14and the incorporation of the amino acid into protein were diminished in the presence of low concentrations of CCl4. These findings and the changes observed after CCl4administration in vivo are compared, and support is found for the view that CCl4affects hepatic metabolism in vivo directly.