Relationships between concentration of hepatic intermediary metabolites and induction of the key glycolytic enzymes in vivo.

1. The time-course for the induction of hepatic glucokinase, hexokinase, phosphofructokinase, liver-type and muscle-type pyruvate kinases in reponse to various diets and insulin has been investigated over the first 48h of change in both diabetic and non-diabetic rats. 2. The results are consistent with there being separate regulatory mechanisms for the induction of each of the three key enzymes, that is for glucokinase, phosphofructokinase and liver-type pyruvate kinase. 3. To investigate the possibility that induction of these enzymes is mediated through specific metabolites a full metabolite profile has been determined under conditions identical with those in the induction experiments and the results examined for correlations between metabolite concentrations and enzyme activities. 4. Several such relationships were detected and those between glucokinase activity and the phosphorylation state of the adenine nucleotides and between liver-type pyruvate kinase activity and the concentrations of dihydroxyacetone phosphate and pyruvate are discussed in relation to the concept of inducing metabolites. 5. It is suggested that the induction of glycolytic enzymes by insulin may be secondary to the changes in the concentration of specific hepatic metabolites brought about by the acute effects of the hormone. 6. The details of the metabolite concentrations in the various experimental states have been deposited as Supplementary Publication SUP 50021 at the British Library (Lending Division) (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1973), 131, 5.