ATP synthesis kinetics and mitochondrial function in the postischemic myocardium as studied by 31P NMR

Edward Y Sako, P. B. Kingsley-Hickman, A. H L From, J. E. Foker, K. Ugurbil

Research output: Contribution to journalArticle

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Abstract

The effects of ischemia on mitochondrial function and the unidirectional rate of ATP synthesis (P(i) → ATP rate) were studied using a Langendorff-perfused heart preparation and 31P NMR spectroscopy. There was significant postischemic depression of mechanical function assessed as the heart rate pressure product, and the myocardial oxygen consumption rate at a given rate pressure product was elevated. Experiments performed on glucose- and pyruvate-perfused hearts demonstrated the presence of a large contribution to the unidirectional P(i) → ATP rate catalyzed by glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase. This rate was much greater than the maximal glucose utilization rate in the myocardium, demonstrating that the glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase reactions are near equilibrium both before and after ischemia. In the pyruvate-perfused postischemic hearts, the glycolytic contribution was eliminated and the net rate of ATP synthesis by oxidative phosphorylation was measurable. Despite the reduced mechanical function and increased myocardial oxygen consumption rate, the ratio of the net rate of ATP synthesis by oxidative phosphorylation to oxygen consumption rate (the P:O ratio) was not altered subsequent to ischemia (2.34 ± 0.12 and 2.36 ± 0.09 in normal and postischemic hearts, respectively). Therefore, mitochondrial uncoupling cannot be the cause of postischemic depression in mechanical function; instead, the data suggest the existence of ischemia-induced inefficiency in ATP utilization.

Original languageEnglish (US)
Pages (from-to)10600-10607
Number of pages8
JournalJournal of Biological Chemistry
Volume263
Issue number22
StatePublished - 1988
Externally publishedYes

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Myocardium
Adenosine Triphosphate
Nuclear magnetic resonance
Kinetics
Ischemia
Oxygen Consumption
Phosphoglycerate Kinase
Glyceraldehyde-3-Phosphate Dehydrogenases
Oxidative Phosphorylation
Oxygen
Pyruvic Acid
Pressure
Glucose
Nuclear magnetic resonance spectroscopy
Magnetic Resonance Spectroscopy
Heart Rate
Experiments

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sako, E. Y., Kingsley-Hickman, P. B., From, A. H. L., Foker, J. E., & Ugurbil, K. (1988). ATP synthesis kinetics and mitochondrial function in the postischemic myocardium as studied by 31P NMR. Journal of Biological Chemistry, 263(22), 10600-10607.

ATP synthesis kinetics and mitochondrial function in the postischemic myocardium as studied by 31P NMR. / Sako, Edward Y; Kingsley-Hickman, P. B.; From, A. H L; Foker, J. E.; Ugurbil, K.

In: Journal of Biological Chemistry, Vol. 263, No. 22, 1988, p. 10600-10607.

Research output: Contribution to journalArticle

Sako, EY, Kingsley-Hickman, PB, From, AHL, Foker, JE & Ugurbil, K 1988, 'ATP synthesis kinetics and mitochondrial function in the postischemic myocardium as studied by 31P NMR', Journal of Biological Chemistry, vol. 263, no. 22, pp. 10600-10607.
Sako, Edward Y ; Kingsley-Hickman, P. B. ; From, A. H L ; Foker, J. E. ; Ugurbil, K. / ATP synthesis kinetics and mitochondrial function in the postischemic myocardium as studied by 31P NMR. In: Journal of Biological Chemistry. 1988 ; Vol. 263, No. 22. pp. 10600-10607.
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