title: 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.
abstract: 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.
authors.affiliation: Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland. seuping.guiraud@rd.nestle.com.
authors.forename: Seu Ping
authors.initials: SP
authors.lastname: Guiraud
authors.affiliation: Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
authors.forename: Ivan
authors.initials: I
authors.lastname: Montoliu
authors.affiliation: Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
authors.forename: Laeticia
authors.initials: L
authors.lastname: Da Silva
authors.affiliation: Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
authors.forename: Loïc
authors.initials: L
authors.lastname: Dayon
authors.affiliation: Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
authors.forename: Antonio Núñez
authors.initials: AN
authors.lastname: Galindo
authors.affiliation: Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
authors.forename: John
authors.initials: J
authors.lastname: Corthésy
authors.affiliation: Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Kussmann
authors.affiliation: Nestlé Institute of Health Sciences SA, Campus EPFL, Innovation Park, CH-1015, Lausanne, Switzerland.
authors.forename: Francois-Pierre
authors.initials: FP
authors.lastname: Martin
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods; D006710:Homocysteine / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000378:metabolism; D006801:Humans; D007201:Indicator Dilution Techniques; D057230:Limit of Detection; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods*; D008715:Methionine / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008875:Middle Aged; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D006710:Homocysteine; D008715:Methionine
keywords: Cerebrospinal fluid; High throughput; LC–MS/MS; Methionine pathway; One-carbon metabolism; Plasma