Regulation of myocardial energy metabolism.
Closed aorta working hearts perfused with 1 mM pyruvate were subjected to a 4-fold increase in work load by raising the left atrial filling pressure. Citric acid cycle flux, pyruvate uptake, and oxygen consumption rose 3-fold when cardiac output was increased. In the first 40 sec after the transition tissue glutamate and citrate fell by 22 and 45%, respectively, and there were reciprocal decreases in malate and aspartate. The ratio of creatine phosphate/creatine declined by 50% within 30 sec, with a corresponding increase in inorganic phosphate, but the fall in the ATP/ADP ratio was only 10%. During the first 10 sec the surface fluorescence from cardiac pyridine nucleotides fell by 30% and this change was synchronous with a sharp decline in the calculated adenine nucleotide phosphate potential. This suggests that heart mitochondrial respiration is controlled by the cytosolic phosphate potential, and that a state 4 to state 3 transition occurs when cardiac output is increased. Apparent disequilbrium of creatine phosphokinase can be explained by the compartmentation of most of the cardiac ADP within the mitochondria. Citric acid cycle flux was coordinated by activational interactions at citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase, but a transient imbalance between the individual cycle steps leads to a sharp peak of lactate production shortly after the work transition.
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000227:Adenine Nucleotides / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D002952:Citric Acid Cycle; D003065:Coenzyme A / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004734:Energy Metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D007773:Lactates / Q000096:biosynthesis; D008293:Malates / Q000378:metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D010101:Oxygen Consumption; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D013386:Succinates / Q000378:metabolism
D000227:Adenine Nucleotides; D007656:Ketoglutaric Acids; D007773:Lactates; D008293:Malates; D011773:Pyruvates; D013386:Succinates; D009243:NAD; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000105:Acetyl Coenzyme A; D003065:Coenzyme A