Creatine kinase kinetics, ATP turnover, and cardiac performance in hearts depleted of creatine with the substrate analogue beta-guanidinopropionic acid.
Rats were fed a diet containing 1% of the creatine substrate analogue beta-guanidinopropionic acid for 6-10 weeks. 31P-NMR investigation of isolated, glucose-perfused working hearts showed a 90% reduction in [phosphocreatine] from 22.2 to 2.5 mumol/g dry wt in guanidinopropionic acid-fed animals but no change in [Pi], [ATP], or intracellular pH. The unidirectional exchange flux in the creatine kinase reaction (direction phosphocreatine----ATP) was measured by saturation transfer NMR in hearts working against a perfusion pressure of 70 cm of water. This exchange was 10 mumol/g dry wt per s in control hearts and decreased 4-fold to 2.5-2.8 mumol/g dry wt per s in hearts from guanidinopropionic acid-fed animals. Oxygen consumption and cardiac performance were measured in parallel experiments at two perfusion pressures, 70 and 140 cm. No significant differences were observed in oxygen uptake or in any of the performance criteria between hearts from control and guanidinopropionic acid-fed rats at either workload. Assuming an ADP:O ratio of 3, the oxygen consumption measurements correspond to ATP turnover rates of 4.2-7.8 mumol/g dry per s. These rates are 1.5-3-times greater than the rate of the phosphocreatine----ATP exchange in hearts from guanidinopropionic acid-fed rats. These data suggest that phosphocreatine cannot be an obligate intermediate of energy transduction in the heart.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003401:Creatine / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism*; D004734:Energy Metabolism; D006146:Guanidines / Q000378:metabolism*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D011422:Propionates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D006146:Guanidines; D011422:Propionates; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D003401:Creatine; C005775:guanidinopropionic acid