Control of Glycolytic Enzyme Synthesis in Yeast by Products of the Hexokinase Reaction

Abstract Addition of 2-deoxyglucose to a culture of the hybrid yeast Saccharomyces fragilis x Saccharomyces dobzhanskii causes 2- to 200-fold increase in the differential rate of synthesis of all glycolytic enzymes except alcohol dehydrogenase (EC 1.1.1.1). For most enzymes, the stimulation in the rate of synthesis occurs with a delay. The greatest stimulation is observed in the case of glyceraldehyde-3-P dehydrogenase (EC 1.2.1.12), viz. about 200-fold, while P-glycerate mutase (EC 2.7.5.3) and enolase (EC 4.2.1.11) show a 2.5-fold increase in the differential rate of synthesis. Glucosone also stimulates the rate of synthesis of hexokinase (EC 2.7.1.1) and glyceraldehyde-3-P dehydrogenase. Generally, glycolytic enzyme synthesis is elicited by all compounds studied which are substrates of yeast hexokinase, while 6-deoxyglucose fails to induce synthesis either in the hybrid yeast or in Saccharomyces cerevisiae. The loss of fructose-phosphorylating activity in a hexokinaseless mutant of this yeast is associated with the failure of fructose to induce any of the glycolytic enzymes that fructose induces in the wild type. The differential rates of synthesis of all of the glycolytic enzymes between aldolase (EC 4.1.2.7) and pyruvate kinase (EC 2.7.1.40) increase 6- to 150-fold over the basal rates when glucose is added to a P-glucoisomerase (EC 5.3.1.9)-deficient mutant of S. cerevisiae. Experiments with a P-mannoisomerase (EC 5.3.1.8)-deficient mutant of S. cerevisiae indicate that hexokinase and P-fructokinase (EC 2.7.1.11) synthesis is stimulated in response to the presence of mannose. These and other data on the metabolites produced from 2-deoxyglucose have been interpreted to suggest that glucose-6-P is the inducer of the following enzymes: aldolase, triose-P isomerase (EC 5.3.1.1), glyceraldehyde-3-P dehydrogenase, P-glycerate kinase (EC 2.7.2.3), P-glycerate mutase, enolase, and pyruvate kinase. Mannose-6-P is the inducer of hexokinase and, presumably, of P-fructokinase. Pyruvate decarboxylase (EC 4.7.1.1) does not appear to be induced by glucose-6-P. These data are also consistent with P-glucomutase (EC 2.7.5.1) being induced by glucose-1-P.