The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C 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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2012
|
| _version_ | 1797057107720142848 |
|---|---|
| author | Schroeder, M Atherton, H Dodd, M Lee, P Cochlin, L Radda, G Clarke, K Tyler, D |
| author_facet | Schroeder, M Atherton, H Dodd, M Lee, P Cochlin, L Radda, G Clarke, K Tyler, D |
| author_sort | Schroeder, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:31:35Z |
| format | Journal article |
| id | oxford-uuid:1da1d45e-6d5a-494b-9484-e72a83c2bb37 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:31:35Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:1da1d45e-6d5a-494b-9484-e72a83c2bb372022-03-26T11:12:12ZThe cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1da1d45e-6d5a-494b-9484-e72a83c2bb37EnglishSymplectic Elements at Oxford2012Schroeder, MAtherton, HDodd, MLee, PCochlin, LRadda, GClarke, KTyler, DBACKGROUND: 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. |
| spellingShingle | Schroeder, M Atherton, H Dodd, M Lee, P Cochlin, L Radda, G Clarke, K Tyler, D The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study. |
| title | The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study. |
| title_full | The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study. |
| title_fullStr | The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study. |
| title_full_unstemmed | The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study. |
| title_short | The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study. |
| title_sort | cycling of acetyl coenzyme a through acetylcarnitine buffers cardiac substrate supply a hyperpolarized 13c magnetic resonance study |
| work_keys_str_mv | AT schroederm thecyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT athertonh thecyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT doddm thecyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT leep thecyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT cochlinl thecyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT raddag thecyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT clarkek thecyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT tylerd thecyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT schroederm cyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT athertonh cyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT doddm cyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT leep cyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT cochlinl cyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT raddag cyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT clarkek cyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy AT tylerd cyclingofacetylcoenzymeathroughacetylcarnitinebufferscardiacsubstratesupplyahyperpolarized13cmagneticresonancestudy |