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

doi:10.1152/ajpheart.00976.2003

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

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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 (V_TCA) and exchange flux (V_X) that involved cycle intermediates were both sensitive to cell redox and altered Ca²⁺ concentration, and the ratio of these fluxes (V_X/V_TCA) varied > 10-fold.

Original language	English (US)
Pages (from-to)	H889-H895
Journal	American Journal of Physiology - Heart and Circulatory Physiology
Volume	287
Issue number	2 56-2
DOIs	https://doi.org/10.1152/ajpheart.00976.2003
State	Published - Aug 2004

Keywords

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

ASJC Scopus subject areas

Physiology
Cardiology and Cardiovascular Medicine
Physiology (medical)

Access to Document

10.1152/ajpheart.00976.2003

Cite this

@article{d42a0c014baf44629010f307a3ff7279,

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

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.",

keywords = "C nuclear magnetic resonance, Extracellular calcium concentration, Intermediary metabolism, Malate-aspartate shuttle, Modeling, Tricarboxylic acid cycle",

author = "Carvalho, {Rui A.} and Rodrigues, {Tiago B.} and Piyu Zhao and Jeffrey, {F. Mark H} and Malloy, {Craig R.} and Sherry, {A. Dean}",

year = "2004",

month = aug,

doi = "10.1152/ajpheart.00976.2003",

language = "English (US)",

volume = "287",

pages = "H889--H895",

journal = "American Journal of Physiology - Heart and Circulatory Physiology",

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T1 - A 13C isotopomer kinetic analysis of cardiac metabolism

T2 - Influence of altered cytosolic redox and [Ca2+]o

AU - Carvalho, Rui A.

AU - Rodrigues, Tiago B.

AU - Zhao, Piyu

AU - Jeffrey, F. Mark H

AU - Malloy, Craig R.

AU - Sherry, A. Dean

PY - 2004/8

Y1 - 2004/8

N2 - 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.

AB - 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.

KW - C nuclear magnetic resonance

KW - Extracellular calcium concentration

KW - Intermediary metabolism

KW - Malate-aspartate shuttle

KW - Modeling

KW - Tricarboxylic acid cycle

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