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

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

Research output: Contribution to journalArticle

40 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)33-40
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume201
Issue number1-2
DOIs
StatePublished - 1999

Keywords

  • Adenylate kinase
  • Cardiomyopathy
  • Creatine kinase
  • Energy signaling
  • Glycolysis
  • Heart failure
  • Phosphotransfer

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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