Salvage mechanisms for regeneration of adenosine triphosphate in rat cardiac myocytes.
Since mitochondrial oxidative phosphorylation does not produce sufficient adenosine triphosphate for rapid restoration of contractile function in myocardium reoxygenated after ischaemia alternative non-oxidative routes by which purine nucleosides or bases may be used to increase the cytoplasmic adenine nucleotide pool were studied. Comparative rates of uptake and salvage of adenosine, adenine, and hypoxanthine were determined using myocytes isolated from adult rat heart. For each precursor reactions limiting the overall rate at which substrate in the extracellular fluid is incorporated into the intracellular adenosine triphosphate pool were identified. Adenosine was salvaged at twice the rate seen with adenine in the presence of ribose, whereas the rate of salvage of hypoxanthine, in the presence of ribose, was only 5% of that for adenosine. Adenine may be an advantageous substrate since high concentrations of adenine are not inhibitory to salvage and do not influence cardiac haemodynamics. Salvage of hypoxanthine appeared to be limited by the rate of adenylosuccinate synthetase, which was present at less than 1% of the adenylosuccinase rate in rat, rabbit, and beef heart. In addition, since salvage of bases is dependent on the availability of phosphoribosylpyrophosphate rates of synthesis of phosphoribosylpyrophosphate were measured in whole myocytes from ribose and in cytoplasmic extracts from ribose and from ribose-5-phosphate. Metabolic sites were identified at which interventions designed to accelerate salvage rates might best be directed.
D000225:Adenine / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000248:Adenosine Kinase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007700:Kinetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010754:Phosphoribosyl Pyrophosphate / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D010754:Phosphoribosyl Pyrophosphate; D000255:Adenosine Triphosphate; D000248:Adenosine Kinase; D000225:Adenine; D000241:Adenosine