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Is N,N-dimethylglycine N-oxide a choline and betaine metabolite?

  • Michael Lever EMAIL logo , Christopher J. McEntyre , Peter M. George and Stephen T. Chambers
Published/Copyright: November 30, 2016

Abstract

Choline metabolism is by oxidation to betaine, which is demethylated to N,N-dimethylglycine; dimethylglycine is oxidatively demethylated to sarcosine. This pathway is important for osmoregulation and as a source of methyl groups. We asked whether another metabolite was involved. We synthesized the N-oxide of dimethylglycine (DMGO) by oxidizing dimethylglycine with peracetic acid, and measured DMGO in human plasma and urine by HPLC-MS/MS with positive ion detection, using two chromatography procedures, based on ion exchange and HILIC separations. The molecular ion DMGOH+ (m/z=120) yielded four significant fragments (m/z=103, 102, 58 and 42). The suspected DMGO peak in human body fluids showed all these fragments, and co-chromatographed with added standard DMGO in both HPLC systems. Typical plasma concentrations of DMGO are under 1 μmol/l. They may be lower in metabolic syndrome patients. Urine concentrations are higher, and DMGO has a higher fractional clearance than dimethylglycine, betaine and choline. It was present in all of over 80 human urine and plasma samples assayed. Plasma DMGO concentrations correlate with plasma DMG concentrations, with betaine and choline concentrations, with the osmolyte myo-inositol, and strongly with urinary DMGO excretion. We conclude that DMGO is probably a normal human metabolite.

Acknowledgements

The study involving 16 healthy students was funded by the Heart Foundation of New Zealand. The study of metabolic syndrome subjects was funded by DuPont Nutrition & Health. The funding bodies had no influence on this study.

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Received: 2016-7-31
Accepted: 2016-11-24
Published Online: 2016-11-30
Published in Print: 2017-6-27

©2017 Walter de Gruyter GmbH, Berlin/Boston

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