Analysis of S-Adenosylmethionine and S-Adenosylhomocysteine: Method Optimisation and Profiling in Healthy Adults upon Short-Term Dietary Intervention

S-adenosylmethionine (SAM) is essential for methyl transfer reactions. All SAM is produced de novo via the methionine cycle. The demethylation of SAM produces S-adenosylhomocysteine (SAH), an inhibitor of methyltransferases and the precursor of homocysteine (Hcy). The measurement of SAM and SAH in p...

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Main Authors: Aida Corrillero Bravo, Maria Nieves Ligero Aguilera, Nahuel R. Marziali, Lennart Moritz, Victoria Wingert, Katharina Klotz, Anke Schumann, Sarah C. Grünert, Ute Spiekerkoetter, Urs Berger, Ann-Kathrin Lederer, Roman Huber, Luciana Hannibal
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Language:English
Published: MDPI AG 2022-04-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/12/5/373
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author Aida Corrillero Bravo
Maria Nieves Ligero Aguilera
Nahuel R. Marziali
Lennart Moritz
Victoria Wingert
Katharina Klotz
Anke Schumann
Sarah C. Grünert
Ute Spiekerkoetter
Urs Berger
Ann-Kathrin Lederer
Roman Huber
Luciana Hannibal
author_facet Aida Corrillero Bravo
Maria Nieves Ligero Aguilera
Nahuel R. Marziali
Lennart Moritz
Victoria Wingert
Katharina Klotz
Anke Schumann
Sarah C. Grünert
Ute Spiekerkoetter
Urs Berger
Ann-Kathrin Lederer
Roman Huber
Luciana Hannibal
author_sort Aida Corrillero Bravo
collection DOAJ
description S-adenosylmethionine (SAM) is essential for methyl transfer reactions. All SAM is produced de novo via the methionine cycle. The demethylation of SAM produces S-adenosylhomocysteine (SAH), an inhibitor of methyltransferases and the precursor of homocysteine (Hcy). The measurement of SAM and SAH in plasma has value in the diagnosis of inborn errors of metabolism (IEM) and in research to assess methyl group homeostasis. The determination of SAM and SAH is complicated by the instability of SAM under neutral and alkaline conditions and the naturally low concentration of both SAM and SAH in plasma (nM range). Herein, we describe an optimised LC-MS/MS method for the determination of SAM and SAH in plasma, urine, and cells. The method is based on isotopic dilution and employs 20 µL of plasma or urine, or 500,000 cells, and has an instrumental running time of 5 min. The reference ranges for plasma SAM and SAH in a cohort of 33 healthy individuals (age: 19–60 years old; mean ± 2 SD) were 120 ± 36 nM and 21.5 ± 6.5 nM, respectively, in accordance with independent studies and diagnostic determinations. The method detected abnormal concentrations of SAM and SAH in patients with inborn errors of methyl group metabolism. Plasma and urinary SAM and SAH concentrations were determined for the first time in a randomised controlled trial of 53 healthy adult omnivores (age: 18–60 years old), before and after a 4 week intervention with a vegan or meat-rich diet, and revealed preserved variations of both metabolites and the SAM/SAH index.
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spelling doaj.art-bcd3cb3eafaf4bafb1d28654223821222023-11-23T12:06:27ZengMDPI AGMetabolites2218-19892022-04-0112537310.3390/metabo12050373Analysis of S-Adenosylmethionine and S-Adenosylhomocysteine: Method Optimisation and Profiling in Healthy Adults upon Short-Term Dietary InterventionAida Corrillero Bravo0Maria Nieves Ligero Aguilera1Nahuel R. Marziali2Lennart Moritz3Victoria Wingert4Katharina Klotz5Anke Schumann6Sarah C. Grünert7Ute Spiekerkoetter8Urs Berger9Ann-Kathrin Lederer10Roman Huber11Luciana Hannibal12Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyLaboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyLaboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyLaboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyLaboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyLaboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyLaboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyDepartment of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyDepartment of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyLaboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyCenter for Complementary Medicine, Department of Internal Medicine II, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyCenter for Complementary Medicine, Department of Internal Medicine II, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyLaboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyS-adenosylmethionine (SAM) is essential for methyl transfer reactions. All SAM is produced de novo via the methionine cycle. The demethylation of SAM produces S-adenosylhomocysteine (SAH), an inhibitor of methyltransferases and the precursor of homocysteine (Hcy). The measurement of SAM and SAH in plasma has value in the diagnosis of inborn errors of metabolism (IEM) and in research to assess methyl group homeostasis. The determination of SAM and SAH is complicated by the instability of SAM under neutral and alkaline conditions and the naturally low concentration of both SAM and SAH in plasma (nM range). Herein, we describe an optimised LC-MS/MS method for the determination of SAM and SAH in plasma, urine, and cells. The method is based on isotopic dilution and employs 20 µL of plasma or urine, or 500,000 cells, and has an instrumental running time of 5 min. The reference ranges for plasma SAM and SAH in a cohort of 33 healthy individuals (age: 19–60 years old; mean ± 2 SD) were 120 ± 36 nM and 21.5 ± 6.5 nM, respectively, in accordance with independent studies and diagnostic determinations. The method detected abnormal concentrations of SAM and SAH in patients with inborn errors of methyl group metabolism. Plasma and urinary SAM and SAH concentrations were determined for the first time in a randomised controlled trial of 53 healthy adult omnivores (age: 18–60 years old), before and after a 4 week intervention with a vegan or meat-rich diet, and revealed preserved variations of both metabolites and the SAM/SAH index.https://www.mdpi.com/2218-1989/12/5/373S-adenosylmethionineS-adenosylhomocysteinemethioninecobalaminfolatehomocysteine
spellingShingle Aida Corrillero Bravo
Maria Nieves Ligero Aguilera
Nahuel R. Marziali
Lennart Moritz
Victoria Wingert
Katharina Klotz
Anke Schumann
Sarah C. Grünert
Ute Spiekerkoetter
Urs Berger
Ann-Kathrin Lederer
Roman Huber
Luciana Hannibal
Analysis of S-Adenosylmethionine and S-Adenosylhomocysteine: Method Optimisation and Profiling in Healthy Adults upon Short-Term Dietary Intervention
Metabolites
S-adenosylmethionine
S-adenosylhomocysteine
methionine
cobalamin
folate
homocysteine
title Analysis of S-Adenosylmethionine and S-Adenosylhomocysteine: Method Optimisation and Profiling in Healthy Adults upon Short-Term Dietary Intervention
title_full Analysis of S-Adenosylmethionine and S-Adenosylhomocysteine: Method Optimisation and Profiling in Healthy Adults upon Short-Term Dietary Intervention
title_fullStr Analysis of S-Adenosylmethionine and S-Adenosylhomocysteine: Method Optimisation and Profiling in Healthy Adults upon Short-Term Dietary Intervention
title_full_unstemmed Analysis of S-Adenosylmethionine and S-Adenosylhomocysteine: Method Optimisation and Profiling in Healthy Adults upon Short-Term Dietary Intervention
title_short Analysis of S-Adenosylmethionine and S-Adenosylhomocysteine: Method Optimisation and Profiling in Healthy Adults upon Short-Term Dietary Intervention
title_sort analysis of s adenosylmethionine and s adenosylhomocysteine method optimisation and profiling in healthy adults upon short term dietary intervention
topic S-adenosylmethionine
S-adenosylhomocysteine
methionine
cobalamin
folate
homocysteine
url https://www.mdpi.com/2218-1989/12/5/373
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