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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©2017 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Reviews
- Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumours
- The cancer cell adhesion resistome: mechanisms, targeting and translational approaches
- Research Articles/Short Communications
- Protein Structure and Function
- Mitochondrial cytochrome c oxidase is inhibited by ATP only at very high ATP/ADP ratios
- Novel domain architectures and functional determinants in atypical annexins revealed by phylogenomic analysis
- Molecular Medicine
- Plasmin(ogen) serves as a favorable biomarker for prediction of survival in advanced high-grade serous ovarian cancer
- Cell Biology and Signaling
- Is N,N-dimethylglycine N-oxide a choline and betaine metabolite?
- Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1
- Intra- or extra-exosomal secretion of HDGF isoforms: the extraordinary function of the HDGF-A N-terminal peptide
- Erratum
- Erratum to: Tropane alkaloids as substrates and inhibitors of human organic cation transporters of the SLC22 (OCT) and the SLC47 (MATE) families
Articles in the same Issue
- Frontmatter
- Reviews
- Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumours
- The cancer cell adhesion resistome: mechanisms, targeting and translational approaches
- Research Articles/Short Communications
- Protein Structure and Function
- Mitochondrial cytochrome c oxidase is inhibited by ATP only at very high ATP/ADP ratios
- Novel domain architectures and functional determinants in atypical annexins revealed by phylogenomic analysis
- Molecular Medicine
- Plasmin(ogen) serves as a favorable biomarker for prediction of survival in advanced high-grade serous ovarian cancer
- Cell Biology and Signaling
- Is N,N-dimethylglycine N-oxide a choline and betaine metabolite?
- Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1
- Intra- or extra-exosomal secretion of HDGF isoforms: the extraordinary function of the HDGF-A N-terminal peptide
- Erratum
- Erratum to: Tropane alkaloids as substrates and inhibitors of human organic cation transporters of the SLC22 (OCT) and the SLC47 (MATE) families