Structural elucidation of novel biomarkers of known metabolic disorders based on multistage fragmentation mass spectra

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F18%3A73581802" target="_blank" >RIV/61989592:15110/18:73581802 - isvavai.cz</a>

Alternative codes found

RIV/00098892:_____/18:N0000001

Result on the web

<a href="https://link.springer.com/content/pdf/10.1007%2Fs10545-017-0109-4.pdf" target="_blank" >https://link.springer.com/content/pdf/10.1007%2Fs10545-017-0109-4.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10545-017-0109-4" target="_blank" >10.1007/s10545-017-0109-4</a>

Result language

angličtina

Original language name

Structural elucidation of novel biomarkers of known metabolic disorders based on multistage fragmentation mass spectra

Original language description

Specific diagnostic markers are the key to effective diagnosis and treatment of inborn errors of metabolism (IEM). Untargeted metabolomics allows for the identification of potential novel diagnostic biomarkers. Current separation techniques coupled to high-resolution mass spectrometry provide a powerful tool for structural elucidation of unknown compounds in complex biological matrices. This is a proof-of-concept study testing this methodology to determine the molecular structure of as yet uncharacterized m/z signals that were significantly increased in plasma samples from patients with phenylketonuria and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. A hybrid linear ion trap-orbitrap high resolution mass spectrometer, capable of multistage fragmentation, was used to acquire accurate masses and product ion spectra of the uncharacterized m/z signals. In order to determine the molecular structures, spectral databases were searched and fragmentation prediction software was used. This approach enabled structural elucidation of novel compounds potentially useful as biomarkers in diagnostics and follow-up of IEM patients. Two new conjugates, glutamyl-glutamyl-phenylalanine and phenylalanine-hexose, were identified in plasma of phenylketonuria patients. These novel markers showed high inter-patient variation and did not correlate to phenylalanine levels, illustrating their potential added value for follow-up. As novel biomarkers for 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, three positional isomers of 3-methylglutaconyl carnitine could be detected in patient plasma. Our results highlight the applicability of current accurate mass multistage fragmentation techniques for structural elucidation of unknown metabolites in human biofluids, offering an unprecedented opportunity to gain further biochemical insights in known inborn errors of metabolism by enabling high confidence identification of novel biomarkers.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

JOURNAL OF INHERITED METABOLIC DISEASE

ISSN

0141-8955

e-ISSN

—

Volume of the periodical

41

Issue of the periodical within the volume

3

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

8

Pages from-to

407-414

UT code for WoS article

000432732200011

EID of the result in the Scopus database

2-s2.0-85033729606