A 13C isotopomer kinetic analysis of cardiac metabolism: Influence of altered cytosolic redox and [Ca2+]o

Rui A. Carvalho, Tiago B. Rodrigues, Piyu Zhao, F. Mark H Jeffrey, Craig R. Malloy, A. Dean Sherry

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Abstract

Rat hearts were perfused with mixtures of [3-13C]pyruvate and [3-13C]lactate (to alter cytosolic redox) at low (0.5 mM) or high (2.5 mM) Ca2+ concentrations to alter contractility. Hearts were frozen at various times after exposure to these substrates, were extracted, and were then analyzed by 13C NMR spectroscopy. The time-dependent multiplets observed in the 13C NMR resonances of glutamate in all hearts and in malate and aspartate in hearts perfused with high-pyruvate/low- lactate concentrations were analyzed using a kinetic model of the tricarboxylic acid (TCA) cycle. The analysis showed that TCA cycle flux (VTCA) and exchange flux (VX) that involved cycle intermediates were both sensitive to cell redox and altered Ca2+ concentration, and the ratio of these fluxes (VX/VTCA) varied > 10-fold.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number2 56-2
DOIs
Publication statusPublished - Aug 2004

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Keywords

  • C nuclear magnetic resonance
  • Extracellular calcium concentration
  • Intermediary metabolism
  • Malate-aspartate shuttle
  • Modeling
  • Tricarboxylic acid cycle

ASJC Scopus subject areas

  • Physiology

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