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 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.
Dzeja
P P
PP
Department of Internal Medicine and Pharmacology, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA.
Pucar
D
D
Redfield
M M
MM
Burnett
J C
JC
Terzic
A
A
D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D002256:Carbonic Anhydrases / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004285:Dogs; D004798:Enzymes / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006593:Hexokinase / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010735:Phosphoglycerate Kinase / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D012016:Reference Values; D016277:Ventricular Function, Left / Q000502:physiology
D004798:Enzymes; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D006593:Hexokinase; D011770:Pyruvate Kinase; D010735:Phosphoglycerate Kinase; D003402:Creatine Kinase; D000263:Adenylate Kinase; D000251:Adenosine Triphosphatases; D002256:Carbonic Anhydrases