Simulation Of Detailed Regulation Of Glycolysis In A Heart Supernatant Preparation

A study of the regulation of the glycolytic pathway has been carried out by simulating in detail the behavior of three glycolyzing beef heart supernatant preparations. Enzyme activity profiles as well as kinetic data on glycolytic intermediates and adenine nucleotides were obtained in the laboratory using glucose-6-phosphate as a substrate. Phosphoglycerate mutase appears to be the limiting enzyme, while triosephosphate isomerase, the most active enzyme when measured separately, is relatively inactive in the complete system. A model consisting of 74 simultaneous differential equations representing 107 chemical reactions were fitted to these results. Incorporated into this model were detailed models of 13 enzymes and crude models of the pentose shunt and ATPase. For most data points, the fit appears fairly good. Most of the enzyme models show strong inhibition as glycolysis proceeds. Individual enzymes were modeled with data from the literature obtained from isolated enzymes. The action of only one enzyme could be satisfactorily simulated without some modification in the form of additional activations, inhibitions, and enzyme-enzyme interactions. This model suggests that the activity of many enzymes is a function of several glycolytic intermediates or products arranged to slow the rate of glycolysis as glycolytic products pile up.