Metabolic Adaptations in Higher Animals

There is a marked increase in the liver glucose 6-phosphatase activity’ of rats fed a diet devoid of a direct source of glucose (1). Also the ingestion of a glucose-free diet containing a high level of protein or fructose causes an increase in liver fructose 1,6-diphosphatase activity in rabbits (2). I f these findings are not special cases, but are representative of a general phenomenon, information about the metabolic pathway of a compound might be obtained by studying changes in the activity of glucose6-Pase and fructose diphosphatase in the livers of animals that had ingested diets in which the compound to be studied had been substituted for glucose. If the substance were converted to glucose independently of phosphorylation in the liver no change would be expected in either the glucose-6-Pase or the fructose diphosphatase activity. I f it were metabolized via glucose-6-P but not fructose-di-P an increase would be expected in the glucase-6-Pase activity. I f it were metabolized via both glucose6-P and fructose-di-P then both the glucose-6-Pase and the fructose diphosphatase activities might be expected to increase. It is noteworthy that both fructose and protein must pass through fructose diphosphate in order to be converted to glucose. The fructose diphosphatase adaptation resembles the glucose6Pase adaptation inasmuch as both are produced in response to a glucogenic stress (2). However, there are some differences in the conditions under which the two adaptations have been studied. These differences are in the species of experimental animal, in the length of time between the start of the experiment and the determination of the activities, and in the nature of the response, i.e. at least part of the increased activity of fructose diphosphatase in the rabbit is a result of activation of a preformed precursor; whereas, the increased glucose-6-Pase activity is apparently a result of protein synthesis (3). Observations on the influence of several types of diets on the activities of liver glucose-6-Pase and fructose diphosphatase and observations on the nature of the fructose diphosphatase response in the rat are presented in this paper.