A comparison of AMP degradation in the perfused rat heart during 2-deoxy-D-glucose perfusion and anoxia. Part I: The release of adenosine and inosine.
AMP degradation is studied in two models of the Langendorff-perfused rat heart which generate a large release of purines: the 2-deoxy-D-glucose (2DG)-perfused heart and the anoxic heart. In the 2DG model, mitochondrial energy generation is quasi-normal, despite a very low ATP concentration. Furthermore, inorganic phosphate (Pi) concentration is low, an important difference with anoxia where Pi is very high, up to 82 mM. Coronary release of purines is measured by high performance liquid chromatography, and myocardial metabolite content by 31P nuclear magnetic resonance spectroscopy. In the 2DG-perfused hearts with glucose or acetate, the purine release consists nearly exclusively of inosine [up to 130 nmol/(min x gww)] while adenosine is less than 1 nmol/(min x gww). A possible interpretation is that AMP degradation proceeds mainly through deamination to inosine monophosphate by AMP deaminase (the IMP pathway). In contrast, the purine release in anoxia (100% N2) contains comparable quantities of adenosine and inosine [respectively 30 and 20 nmol/(min x gww)], indicating that part of AMP is dephosphorylated directly to adenosine. Comparison with the 2DG model suggests that the release of adenosine in the anoxic heart is a result of inhibition of AMP deaminase by Pi.
Chen
W
W
Groupe de Biophysique de l'Ecole Polytechnique et de l'URA D1254 du CNRS, Ecole Polytechnique, Palaiseau, France.
Hoerter
J
J
Guéron
M
M
D000241:Adenosine / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000818:Animals; D000963:Antimetabolites / Q000378:metabolism / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives / Q000096:biosynthesis; D006321:Heart / Q000502:physiology; D006439:Hemodynamics; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D019346:Sodium Acetate / Q000494:pharmacology
D000963:Antimetabolites; C015785:2-deoxyglucose-6-phosphate; D000249:Adenosine Monophosphate; D019346:Sodium Acetate; D019298:Glucose-6-Phosphate; D007288:Inosine; D003847:Deoxyglucose; D005947:Glucose; D000241:Adenosine