Characterization of D-3-hydroxybutyrylcarnitine (ketocarnitine): an identified ketosis-induced metabolite

Metabolism. 2012 Jul;61(7):966-73. doi: 10.1016/j.metabol.2011.11.009. Epub 2011 Dec 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Carnitine / analogs & derivatives*
  • Carnitine / analysis
  • Carnitine / 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
  • Vitamin B Complex / metabolism*
  • Young Adult


  • Fatty Acids
  • Ketone Bodies
  • hydroxybutyrylcarnitine
  • Vitamin B Complex
  • Coenzyme A Ligases
  • Carnitine