Computer simulation of metabolism in pyruvate-perfused rat heart. IV. Model behavior.

The behavior of a computer model of energy metabolism was determined for perfused rat hearts utilizing pyruvate as sole exogenous fuel and subjected to a rapid increase in work load. Computer-generated metabolite profiles, which are solutions of the differential equations for 1 min elapsed time, closely match 12 experimental curves (involving 120 concentration measurements) and exhibit the following properties. The computed cytosolic pyruvate level oscillates due to large changes in the rates of the processes that produce and consume this metabolite. Cytosolic Mg2+ seems to act as a coordinated controller of glycolytic enzymes; its transient increase permits a transient increase of glycolysis without an accumulation of glucose 6-phosphate. Lactate is exported to the interstitium by a lactate permease and then reimported and oxidized. As a result, the malate-aspartate shuttle reverses direction, and the Krebs cycle is "unspanned."