Metabolism of the acutely ischemic dog heart. II. Interpretation of a model.

The glycolytic oscillations occurring in an acutely ischemic dog heart are analyzed with a computer model. The major regulations of the glycolytic pathway flux occur at phosphohexose isomerase, which is inhibited by accumulated pentose shunt intermediates; at phosphorylase, which shapes the first cycle of the oscillation; and at aldolase, which shapes the last two cycles. Aldolase is not under normal substrate control. Its activity, and that of some subsequent glycolytic enzymes, appears to be regulated by known interactions with the muscle proteins. The mitochondria become reduced as a result of anoxia, and their metabolism reorganizes to export rather than import reducing equivalents. It is in general feasible to account for the behavior of this preparation in terms of the known metabolism of less severely perturbed hearts, especially (but not completely) in terms of effects of anoxia. The reasons for the inapplicability of the crossover theorem previously used to analyze this preparation are described.