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High-throughput and simultaneous quantitative analysis of homocysteine-methionine cycle metabolites and co-factors in blood plasma and cerebrospinal fluid by isotope dilution LC-MS/MS.

  • Guiraud SP Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland. seuping.guiraud@rd.nestle.com.
  • Montoliu I Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
  • Da Silva L Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
  • Dayon L Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
  • Galindo AN Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
  • Corthésy J Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
  • Kussmann M Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
  • Martin FP Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
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  • 2016-10-21
Published in:
  • Analytical and bioanalytical chemistry. - 2017
Cerebrospinal fluid
High throughput
LC–MS/MS
Methionine pathway
One-carbon metabolism
Plasma
Chromatography, High Pressure Liquid
High-Throughput Screening Assays
Homocysteine
Humans
Indicator Dilution Techniques
Limit of Detection
Metabolic Networks and Pathways
Metabolomics
Methionine
Middle Aged
Tandem Mass Spectrometry
English The methionine cycle is a key pathway contributing to the regulation of human health, with well-established involvement in cardiovascular diseases and cognitive function. Changes in one-carbon cycle metabolites have also been associated with mild cognitive decline, vascular dementia, and Alzheimer's disease. Today, there is no single analytical method to monitor both metabolites and co-factors of the methionine cycle. To address this limitation, we here report for the first time a new method for the simultaneous quantitation of 17 metabolites in the methionine cycle, which are homocysteic acid, taurine, serine, cysteine, glycine, homocysteine, riboflavin, methionine, pyridoxine, cystathionine, pyridoxamine, S-adenosylhomocysteine, S-adenosylmethionine, betaine, choline, dimethylglycine, and 5-methyltetrahydrofolic acid. This multianalyte method, developed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), provides a highly accurate and precise quantitation of these 17 metabolites for both plasma and cerebrospinal fluid metabolite monitoring. The method requires a simple sample preparation, which, combined with a short chromatographic run time, ensures a high sample throughput. This analytical strategy will thus provide a novel metabolomics approach to be employed in large-scale observational and intervention studies. We expect such a robust method to be particularly relevant for broad and deep molecular phenotyping of individuals in relation to their nutritional requirements, health monitoring, and disease risk management.
Language
  • English
Open access status
hybrid
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Persistent URL
https://fredi.hepvs.ch/global/documents/16168
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