title: The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study.
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.
  
  
  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.
authors.affiliation: Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. marie.schroeder@dpag.ox.ac.uk
authors.forename: Marie A
authors.initials: MA
authors.lastname: Schroeder
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Atherton
authors.forename: Michael S
authors.initials: MS
authors.lastname: Dodd
authors.forename: Phillip
authors.initials: P
authors.lastname: Lee
authors.forename: Lowri E
authors.initials: LE
authors.lastname: Cochlin
authors.forename: George K
authors.initials: GK
authors.lastname: Radda
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Tyler
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000108:Acetylcarnitine / Q000378:metabolism*; D000818:Animals; D002247:Carbon Isotopes; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism*; D019343:Citric Acid / Q000378:metabolism; D004734:Energy Metabolism; D018698:Glutamic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology*; D010084:Oxidation-Reduction; D019518:Postprandial Period; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D002247:Carbon Isotopes; D011768:Pyruvate Dehydrogenase Complex; D019343:Citric Acid; D018698:Glutamic Acid; D000108:Acetylcarnitine; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid; D002332:Carnitine O-Acetyltransferase