1. The effects of premature weaning on to normal and high-glucose diets and of normal weaning on to high-protein and high-fat diets on the activities of hepatic enzymes involved in both the utilization of glucose and the formation of glucose by gluconeogenesis in rats during the weaning period were investigated. 2. The effects of weaning and high-glucose diets were, in general, to bring about increases in the activities of enzymes involved in glucose utilization and a more rapid decrease of the activities of the gluconeogenic enzymes towards normal adult values. 3. The effects of weaning on to high-fat and high-protein diets were, in general, to lower the rate of increase in activities of the enzymes involved in glucose utilization, and to prevent the decrease in activity of the gluconeogenic enzymes that occurs during normal weaning. 4. The changes in the activity of cytoplasmic phosphopyruvate carboxylase appear to be of special significance; this and other results are in keeping with current theories about the pathways and control of gluconeogenesis. 5. The activity of ATP citrate lyase appears to be particularly important in lipid formation. 6. The results are interpreted in terms of the known adaptive behaviour of these enzymes in the adult rat. The roles of enzyme development and of enzyme adaptation in the elaboration of metabolic homoeostasis in the weanling rat are discussed.

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