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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M800221-JLR200 on October 31, 2008

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Journal of Lipid Research, Vol. 50, 1556-1562, August 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Corresponding increase in long-chain acyl-CoA and acylcarnitine after exercise in muscle from VLCAD mice

Frank ter Veld1, Sonja Primassin, Lars Hoffmann, Ertan Mayatepek and Ute Spiekerkoetter

Department of General Pediatrics, Heinrich-Heine-University, Düsseldorf, Germany

1 To whom correspondence should be addressed. email: frank.terveld{at}uni-duesseldorf.de

Long-chain acylcarnitines accumulate in long-chain fatty acid oxidation defects, especially during periods of increased energy demand from fat. To test whether this increase in long-chain acylcarnitines in very long-chain acyl-CoA dehydrogenase (VLCAD–/–) knock-out mice correlates with acyl-CoA content, we subjected wild-type (WT) and VLCAD–/– mice to forced treadmill running and analyzed muscle long-chain acyl-CoA and acylcarnitine with tandem mass spectrometry (MS/MS) in the same tissues. After exercise, long-chain acyl-CoA displayed a significant increase in muscle from VLCAD–/– mice [C16:0-CoA, C18:2-CoA and C18:1-CoA in sedentary VLCAD–/–: 5.95 ± 0.33, 4.48 ± 0.51, and 7.70 ± 0.30 nmol · g–1 wet weight, respectively; in exercised VLCAD–/–: 8.71 ± 0.42, 9.03 ± 0.93, and 14.82 ± 1.20 nmol · g–1 wet weight, respectively (P < 0.05)]. Increase in acyl-CoA in VLCAD-deficient muscle was paralleled by a significant increase in the corresponding chain length acylcarnitine. Exercise resulted in significant lowering of the free carnitine pool in VLCAD–/– muscle. This is the first study demonstrating that acylcarnitines and acyl-CoA directly correlate and concomitantly increase after exercise in VLCAD-deficient muscle.

Supplementary key words β-oxidation • very long-chain acyl-CoA dehydrogenase • acyl-coenzyme A • acylcarnitine

Abbreviations: CPT, cytosolic carnitine palmitoyltransferase; MS/MS, tandem mass spectrometry; WT, wild type; VLCAD, very long-chain acyl-CoA dehydrogenase


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