Metabolic effects of pent-4-enoate in isolated perfused rat heart.
The metabolic effects of the hypoglycaemic agent pent-4-enoate were studied in isolated, beating or potassium-arrested rat hearts. The addition of 0.8mM-pent-4-enoate to the perfusion fluid increased O2 consumption by 76% in the arrested heart and by 14% in the beating heart; the concentration ratio of phosphocreatine/creatine increase concomitantly by 47% and 27% respectively. Perfusion of the heart with pent-4-enoate resulted in a 30-fold increase in the concentration of the pool of tricarboxylic acid-cycle intermediates in the tissue, about 90% of this increase being due to malate. The sum of the concentrations of the myocardial free amino acids remained virtually unchanged during the accumulation of the tricarboxylic acid-cycle intermediates. It was concluded that pent-4-enoate can be effectively metabolized in the myocardium and that its metabolism probably proceeds via propionyl-CoA, since pent-4-enoate reproduces many of the metabolic characteristics of propionate in the cardiac muscle. The accumulation of the tricarboxylic acid-cycle intermediates is probably due to carboxylation of propionyl-CoA. The response pattern of the metabolite concentrations in the cardiac muscle is quite different from that in the liver, in which decrease of the concentrations of the tricarboxylic acid-cycle intermediates has been observed previously [Williamson, Rostand & Peterson (1970) J. Biol. Chem. 245, 3242-3251].
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002208:Caproates / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology*; D002952:Citric Acid Cycle / Q000187:drug effects; D003065:Coenzyme A / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006323:Heart Arrest / Q000378:metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D014631:Valerates / Q000494:pharmacology
D000596:Amino Acids; D002208:Caproates; D002264:Carboxylic Acids; D007773:Lactates; D011773:Pyruvates; D014631:Valerates; D010725:Phosphocreatine; D000105:Acetyl Coenzyme A; D000255:Adenosine Triphosphate; D003401:Creatine; D003065:Coenzyme A