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Dietary Regulation of Pyruvate Kinase Synthesis in Rat Liver¹

Department of Physiological Sciences, School of Veterinary Medicine, University of California, Davis, California

The effects of diet and antibiotics on pyruvate kinase, glucose 6-phosphatase and tyrosine--ketoglutarate transaminase activities were investigated in male Sprague-Dawley rats. Feeding a 90% casein diet to animals pre-fed with a 90% carbohydrate diet for 4 days increased the activities of all 3 enzymes. Force-feeding with casein hydrolysate increased glucose 6-phosphatase, tyrosine--ketoglutarate transaminase and pyruvate kinase activity, though the latter increase was observable only in the animals pre-fed with glucose. The increase in glucose 6-phosphatase activity was partially prevented by actinomycin D and almost totally prevented by cycloheximide. The increase in pyruvate kinase activity (in the animals pre-fed with glucose) was not affected by actinomycin D, but was prevented by cycloheximide. Both antibiotics increased tyrosine--ketoglutarate transaminase activity far beyond the increase caused by force-feeding casein hydrolysate alone. 8-Azaguanine decreased the induction of glucose 6-phosphatase by force-feeding casein hydrolysate without inducing tyrosine--ketoglutarate transaminase or decreasing the induction of the transaminase by actinomycin D or cyclohexamide. Pyruvate kinase activity was induced by force-feeding carbohydrate to rats pre-fed for 5 days with a 90% casein diet. These increases were prevented by both actinomycin D and cycloheximide. Tyrosine--ketoglutarate transaminase was not induced by the antibiotics in these animals. Generally, enzyme activities were higher in the animals pre-fed with fructose, even after force-feeding. The results are in agreement with those for an earlier proposed mechanism of control for the synthesis of pyruvate kinase; that is, the synthesis of this enzyme is controlled at the translational level when the dietary change is from a protein-free to a high protein diet and at the transcriptional level in the case of the high protein to protein-free dietary change.

Manuscript received 5 February 1968.