The Cycling of Acetyl-Coenzyme A Through Acetylcarnitine Buffers Cardiac Substrate Supply A Hyperpolarized 13 C Magnetic Resonance Study
Background— Carnitine acetyltransferase catalyzes the reversible conversion of acetyl-coenzyme A (CoA) into acetylcarnitine. The aim of this study was to use the metabolic tracer hyperpolarized [2- 13 C]pyruvate with magnetic resonance spectroscopy to determine whether carnitine acetyltransferase fa...
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Published in | Circulation. Cardiovascular imaging Vol. 5; no. 2; pp. 201 - 209 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.03.2012
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Abstract | Background—
Carnitine acetyltransferase catalyzes the reversible conversion of acetyl-coenzyme A (CoA) into acetylcarnitine. The aim of this study was to use the metabolic tracer hyperpolarized [2-
13
C]pyruvate with magnetic resonance spectroscopy to determine whether carnitine acetyltransferase facilitates carbohydrate oxidation in the heart.
Methods and Results—
Ex vivo, following hyperpolarized [2-
13
C]pyruvate infusion, the [1-
13
C]acetylcarnitine resonance was saturated with a radiofrequency pulse, and the effect of this saturation on [1-
13
C]citrate and [5-
13
C]glutamate was observed. In vivo, [2-
13
C]pyruvate was infused into 3 groups of fed male Wistar rats: (1) controls, (2) rats in which dichloroacetate enhanced pyruvate dehydrogenase flux, and (3) rats in which dobutamine elevated cardiac workload. In the perfused heart, [1-
13
C]acetylcarnitine saturation reduced the [1-
13
C]citrate and [5-
13
C]glutamate resonances by 63% and 51%, respectively, indicating a rapid exchange between pyruvate-derived acetyl-CoA and the acetylcarnitine pool. In vivo, dichloroacetate increased the rate of [1-
13
C]acetylcarnitine production by 35% and increased the overall acetylcarnitine pool size by 33%. Dobutamine decreased the rate of [1-
13
C]acetylcarnitine production by 37% and decreased the acetylcarnitine pool size by 40%.
Conclusions—
Hyperpolarized
13
C magnetic resonance spectroscopy has revealed that acetylcarnitine provides a route of disposal for excess acetyl-CoA and a means to replenish acetyl-CoA when cardiac workload is increased. Cycling of acetyl-CoA through acetylcarnitine appears key to matching instantaneous acetyl-CoA supply with metabolic demand, thereby helping to balance myocardial substrate supply and contractile function. |
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AbstractList | Background—
Carnitine acetyltransferase catalyzes the reversible conversion of acetyl-coenzyme A (CoA) into acetylcarnitine. The aim of this study was to use the metabolic tracer hyperpolarized [2-
13
C]pyruvate with magnetic resonance spectroscopy to determine whether carnitine acetyltransferase facilitates carbohydrate oxidation in the heart.
Methods and Results—
Ex vivo, following hyperpolarized [2-
13
C]pyruvate infusion, the [1-
13
C]acetylcarnitine resonance was saturated with a radiofrequency pulse, and the effect of this saturation on [1-
13
C]citrate and [5-
13
C]glutamate was observed. In vivo, [2-
13
C]pyruvate was infused into 3 groups of fed male Wistar rats: (1) controls, (2) rats in which dichloroacetate enhanced pyruvate dehydrogenase flux, and (3) rats in which dobutamine elevated cardiac workload. In the perfused heart, [1-
13
C]acetylcarnitine saturation reduced the [1-
13
C]citrate and [5-
13
C]glutamate resonances by 63% and 51%, respectively, indicating a rapid exchange between pyruvate-derived acetyl-CoA and the acetylcarnitine pool. In vivo, dichloroacetate increased the rate of [1-
13
C]acetylcarnitine production by 35% and increased the overall acetylcarnitine pool size by 33%. Dobutamine decreased the rate of [1-
13
C]acetylcarnitine production by 37% and decreased the acetylcarnitine pool size by 40%.
Conclusions—
Hyperpolarized
13
C magnetic resonance spectroscopy has revealed that acetylcarnitine provides a route of disposal for excess acetyl-CoA and a means to replenish acetyl-CoA when cardiac workload is increased. Cycling of acetyl-CoA through acetylcarnitine appears key to matching instantaneous acetyl-CoA supply with metabolic demand, thereby helping to balance myocardial substrate supply and contractile function. |
Author | Cochlin, Lowri E. Lee, Phillip Schroeder, Marie A. Atherton, Helen J. Clarke, Kieran Tyler, Damian J. Dodd, Michael S. Radda, George K. |
Author_xml | – sequence: 1 givenname: Marie A. surname: Schroeder fullname: Schroeder, Marie A. organization: From the Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK – sequence: 2 givenname: Helen J. surname: Atherton fullname: Atherton, Helen J. organization: From the Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK – sequence: 3 givenname: Michael S. surname: Dodd fullname: Dodd, Michael S. organization: From the Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK – sequence: 4 givenname: Phillip surname: Lee fullname: Lee, Phillip organization: From the Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK – sequence: 5 givenname: Lowri E. surname: Cochlin fullname: Cochlin, Lowri E. organization: From the Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK – sequence: 6 givenname: George K. surname: Radda fullname: Radda, George K. organization: From the Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK – sequence: 7 givenname: Kieran surname: Clarke fullname: Clarke, Kieran organization: From the Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK – sequence: 8 givenname: Damian J. surname: Tyler fullname: Tyler, Damian J. organization: From the Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK |
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Cites_doi | 10.1073/pnas.0601319103 10.1016/S0079-6565(97)00024-1 10.1016/S0021-9258(19)68001-4 10.1073/pnas.0805953105 10.1073/pnas.91.23.10771 10.1016/0026-0495(80)90076-1 10.1016/j.jmr.2009.10.003 10.1042/bj1050953 10.1152/ajplegacy.1964.206.3.531 10.1161/circulationaha.111.024919 10.1152/ajplegacy.1966.210.2.385 10.1152/ajpheart.01113.2003 10.1016/S0021-9258(18)97445-4 10.1161/circulationaha.110.011387 10.1056/NEJMra063052 10.1007/s00723-008-0115-7 10.1073/pnas.1733835100 10.1016/0003-9861(55)90515-4 10.1152/ajplegacy.1966.210.2.379 10.1073/pnas.62.1.234 10.1002/nbm.1573 10.1016/S0022-3476(82)80294-1 10.1016/S0021-9258(18)67077-2 10.1016/S0010-4825(01)00006-3 10.1161/01.RES.78.3.482 10.1093/oxfordjournals.humrep.a137835 10.1006/jmcc.1998.0693 10.1016/S0021-9258(19)74465-2 10.1016/S0021-9258(19)57279-9 10.1016/S0021-9258(18)92956-X 10.1113/jphysiol.2004.075713 10.1161/01.RES.77.4.726 10.1074/jbc.M109.066407 10.1016/0003-9861(78)90068-1 10.1096/fj.09-129171 10.1023/A:1006826620218 10.1152/ajpendo.00139.2005 10.1007/BF00800642 |
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Snippet | Background—
Carnitine acetyltransferase catalyzes the reversible conversion of acetyl-coenzyme A (CoA) into acetylcarnitine. The aim of this study was to use... |
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Subtitle | A Hyperpolarized 13 C Magnetic Resonance Study |
Title | The Cycling of Acetyl-Coenzyme A Through Acetylcarnitine Buffers Cardiac Substrate Supply |
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