Characterization of D-3-hydroxybutyrylcarnitine (ketocarnitine): an identified ketosis-induced metabolite.
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.
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD, Amsterdam, the Netherlands. m.r.soeters@amc.uva.nl
Maarten R
MR
Soeters
Mireille J
MJ
Serlie
Hans P
HP
Sauerwein
Marinus
M
Duran
Jos P
JP
Ruiter
Willem
W
Kulik
Mariëtte T
MT
Ackermans
Paul E
PE
Minkler
Charles L
CL
Hoppel
Ronald J A
RJ
Wanders
Sander M
SM
Houten
D000293:Adolescent; D000328:Adult; D002331:Carnitine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D003066:Coenzyme A Ligases / Q000378:metabolism; D005215:Fasting / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007657:Ketone Bodies / Q000378:metabolism; D007662:Ketosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry; D014803:Vitamin B Complex / Q000032:analysis / Q000378:metabolism*; D055815:Young Adult
D005227:Fatty Acids; D007657:Ketone Bodies; C513202:hydroxybutyrylcarnitine; D014803:Vitamin B Complex; D003066:Coenzyme A Ligases; D002331:Carnitine