Abstract |
Hydroxybutyrylcarnitine (HB- carnitine) is a metabolite that has been associated with insulin resistance and type 2 diabetes mellitus. It is currently unknown whether HB- carnitine can be produced from D-3-hydroxybutyrate (D-3HB), a ketone body; but its formation from L-3-HB-CoA, a fatty acid β-oxidation intermediate, is well established. We aimed to assess which stereoisomers of 3-HB-carnitine are present in vivo. Ketosis and increased fatty acid oxidation were induced in 12 lean healthy men by a 38-hour fasting period. The D-3HB kinetics (stable isotope technique) and stereoisomers of muscle 3-HB-carnitine (high-performance liquid chromatography/ultra-performance liquid chromatography-tandem mass spectrometry) were measured. Muscle D-3HB-carnitine content was much higher compared with L-3HB-carnitine. In addition, muscle D-3HB-carnitine correlated significantly with D-3-HB production. Following the finding that a ketone body can be converted into a carnitine ester in vivo, we show in vitro that D-3-HB can be converted into HB- carnitine (ketocarnitine) via an acyl-CoA synthetase reaction in several tissues including human muscle. During fasting, HB- carnitine in muscle is derived mainly from the ketone body D-3HB. The role of D-3HB-carnitine synthesis in metabolism remains to be elucidated.
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Authors | Maarten R Soeters, Mireille J Serlie, Hans P Sauerwein, Marinus Duran, Jos P Ruiter, Willem Kulik, Mariëtte T Ackermans, Paul E Minkler, Charles L Hoppel, Ronald J A Wanders, Sander M Houten |
Journal | Metabolism: clinical and experimental
(Metabolism)
Vol. 61
Issue 7
Pg. 966-73
(Jul 2012)
ISSN: 1532-8600 [Electronic] United States |
PMID | 22209095
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
- Fatty Acids
- Ketone Bodies
- hydroxybutyrylcarnitine
- Vitamin B Complex
- Coenzyme A Ligases
- Carnitine
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Topics |
- Adolescent
- Adult
- Carnitine
(analogs & derivatives, analysis, metabolism)
- Coenzyme A Ligases
(metabolism)
- Fasting
(metabolism)
- Fatty Acids
(metabolism)
- Humans
- Ketone Bodies
(metabolism)
- Ketosis
(metabolism)
- Male
- Middle Aged
- Muscle, Skeletal
(chemistry)
- Vitamin B Complex
(analysis, metabolism)
- Young Adult
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