| The Cycling of Acetyl-CoA through Acetylcarnitine Buffers Cardiac Substrate Supply: A Hyperpolarised 13C Magnetic Resonance Study. | |
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MedLine Citation:
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PMID: 22238215 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: -Carnitine acetyltransferase (CAT) catalyses the reversible conversion of acetyl-CoA into acetylcarnitine. The aim of this study was to use the metabolic tracer hyperpolarised [2-(13)C]pyruvate with magnetic resonance spectroscopy (MRS) to determine if CAT facilitates carbohydrate oxidation in the heart. METHODS AND RESULTS: -Ex vivo, following hyperpolarised [2-(13)C]pyruvate infusion, the [1-(13)C]acetylcarnitine MR 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 three groups of fed male Wistar rats; (a) controls, (b) rats in which dichloroacetate enhanced PDH flux and (c) 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%, indicating 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: -Hyperpolarised (13)C MRS has revealed that acetylcarnitine provides a route of disposal for excess acetyl-CoA, and also 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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Authors:
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Marie A Schroeder; Helen J Atherton; Michael S Dodd; Phillip Lee; Lowri E Cochlin; George K Radda; Kieran Clarke; Damian J Tyler |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-11 |
Journal Detail:
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Title: Circulation. Cardiovascular imaging Volume: - ISSN: 1942-0080 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101479935 Medline TA: Circ Cardiovasc Imaging Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Oxford, Oxford, United Kingdom. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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