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

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Abstract

Coupling of ATP-generating with ATP-consuming processes is an essential component in the cardiac bioenergetics responsible for optimal myocardial function. Although a number of enzymatic systems have been implicated in securing proper intracellular energy communication, their integrative response in a failing myocardium has not been determined so far. Therefore, we measured 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 failing 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 activity of hexokinase, an enzyme which directs phosphoryls into the glycolytic phosphotransfer pathway, was unchanged. Also, the activity of glyceraldehyde-3-phosphate dehydrogenase, which may shuttle inorganic phosphate between ATPases and ATP-synthases, was not affected by heart failure. However, the CO2-hydration activity of carbonic anhydrase, which together with creatine kinase, is presumed responsible for removal of protons from ATPases, was diminished by 21%. As these enzymatic systems are collectively required for adequate delivery of high-energy phosphoryl to, and removal of end-products from, cellular ATPases, the cumulative deficit in their flux capacities may provide a bioenergetic basis for impaired contraction-relaxation in the failing heart.

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Authors and Affiliations

  1. Division of Cardiovascular Diseases, Department of Internal Medicine and Pharmacology, Mayo Clinic, Mayo Foundation, Rochester, MN, 55905, USA

    Petras P. Dzeja, Darko Pucar, Margaret M. Redfield, John C. Burnett & Andre Terzic

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  1. Petras P. Dzeja
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  2. Darko Pucar
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  3. Margaret M. Redfield
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  4. John C. Burnett
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  5. Andre Terzic
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Dzeja, P.P., Pucar, D., Redfield, M.M. et al. Reduced activity of enzymes coupling ATP-generating with ATP-consuming processes in the failing myocardium. Mol Cell Biochem 201, 33–40 (1999). https://doi.org/10.1023/A:1007016703229

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