Reduced activity of enzymes coupling ATP-generating with ATP-consuming processes in the failing myocardium

Coupling of ATP-generating with ATP-consuming processes is an essential com ponent in the cardiac bioenergetics responsible for optimal myocardial func tion. Although a number of enzymatic systems have been implicated in securi ng proper intracellular energy communication, their integrative response in a failing myocardium has not been determined so far. Therefore, we measure d catalytic activities of enzymes responsible for the communication between ATP-generating and ATP-consuming processes in ventricular samples obtained from normal dogs and dogs with tachycardia-induced heart failure. In the f ailing myocardium, phosphotransfer activities of creatine kinase, adenylate kinase, 3-phosphoglycerate kinase and pyruvate kinase, which collectively deliver ATP and remove ADP from myofibrillar ATPases, were depressed by 30, 21, 44 and 20%, respectively, when compared to normal controls. The activi ty of hexokinase, an enzyme which directs phosphoryls into the glycolytic p hosphotransfer pathway, was unchanged. Also, the activity of glyceraldehyde -3-phosphate dehydrogenase, which may shuttle inorganic phosphate between A TPases and ATP-synthases, was not affected by heart failure. However, the C O2-hydration activity of carbonic anhydrase, which together with creatine k inase, is presumed responsible for removal of protons from ATPases, was dim inished by 21%. As these enzymatic systems are collectively required for ad equate delivery of high-energy phosphoryl to, and removal of end-products f rom, cellular ATPases, the cumulative deficit in their flux capacities may provide a bioenergetic basis for impaired contraction-relaxation in the fai ling heart.