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Development of a novel UHPLC-MS/MS-based platform to quantify amines, amino acids and methylarginines for applications in human disease phenotyping.

Abstract：

:Amine quantification is an important strategy in patient stratification and personalised medicine. This is because amines, including amino acids and methylarginines impact on many homeostatic processes. One important pathway regulated by amine levels is nitric oxide synthase (NOS). NOS is regulated by levels of (i) the substrate, arginine, (ii) amino acids which cycle with arginine and (iii) methylarginine inhibitors of NOS. However, biomarker research in this area is hindered by the lack of a unified analytical platform. Thus, the development of a common metabolomics platform, where a wide range of amino acids and methylarginines can be measured constitutes an important unmet need. Here we report a novel high-throughput ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) platform where ≈40 amine analytes, including arginine and methylarginines can be detected and quantified on a molar basis, in a single sample of human plasma. To validate the platform and to generate biomarkers, human plasma from a well-defined cohort of patients before and after coronary artery bypass surgery, who developed systemic inflammatory response syndrome (SIRS), were analysed. Bypass surgery with SIRS significantly altered 26 amine analytes, including arginine and ADMA. Consequently, pathway analysis revealed significant changes in a range of pathways including those associated with NOS.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Ahmetaj-Shala B,Olanipekun M,Tesfai A,MacCallum N,Kirkby NS,Quinlan GJ,Shih CC,Kawai R,Mumby S,Paul-Clark M,Want EJ,Mitchell JA

doi

10.1038/s41598-018-31055-8

subject

Has Abstract

pub_date

2018-09-18 00:00:00

pages

13987

issue

1

issn

2045-2322

pii

10.1038/s41598-018-31055-8

journal_volume

8

pub_type

杂志文章

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