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Regulation of Glucose-6-phosphate Dehydrogenase and 6-Phosphogluconate Dehydrogenase in the Meal-fed Rat¹

Oklahoma Medical Research Foundation and Department of Biochemistry and Molecular Biology, Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma 73104

Meal-feeding of a high sucrose diet produces a diurnal cycle (i.e., food response) in glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) levels resulting in an elevated level of these enzymes at approximately 12 hours after the start of a 2-hour meal and a return to base level by 24 hours. The effects of actinomycin D and cycloheximide on the 12-hour increases in G6PD and 6PGD were determined. Cycloheximide completely blocked the increase in G6PD if administered 2 or 4 hours after start of the meal, while actinomycin D completely blocked the increase in G6PD if administered at 2 hours and almost completely at 4 hours after start of the meal. These results were obtained previously with starved rats refed a sucrose diet. The diurnal increases in G6PD and 6PGD in meal-fed rats and the induction of G6PD in starved-refed rats thus appear to be regulated by the same mechanism; this mechanism requires RNA synthesis within 4 hours after start of refeeding. The response of 6PGD to cycloheximide and to actinomycin D at 2 or 4 hours after start of the meal is essentially the same as that of G6PD. These data suggest that the increases in G6PD and 6PGD (and other enzymes) brought about by carbohydrate refeeding after starvation or by carbohydrate meal-feeding on a diurnal cycle are mediated by a rapid change in RNA sythesis. This appears most compatible with a coordinate control of gene expression through messenger RNA synthesis.

KEY WORDS: • glucose-6-phosphate dehydrogenase • 6-phosphogluconate • sucrose diet • meal-feeding • induction • actinomycin D • cycloheximide

¹ Supported in part by National Institutes of Health Grant HL 12138.

Manuscript received 19 September 1974.