Elucidating the Structure of N1-Acetylisoputreanine: A Novel Polyamine Catabolite in Human Urine

Bryna L. Fitzgerald, Sebabrata Mahapatra, Delphine K. Farmer, Michael R. McNeil, Robert A. Casero, John T. Belisle

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

An untargeted metabolomics approach was utilized to determine urinary metabolites that could serve as small-molecule biomarkers for treatment response to standard tuberculosis treatment. However, the majority of metabolites that most accurately distinguished patient samples at the time of diagnosis from those at 1 month after the start of therapy lacked structural identification. The detection of unknown metabolite structures is a well-known limitation of untargeted metabolomics and underscores a need for continued elucidation of novel metabolite structures. In this study, we sought to define the structure of a urine metabolite with an experimentally determined mass of 202.1326 Da, classified as molecular feature (MF) 202.1326. A hypothesized structure of N1-acetylisoputreanine was developed for MF 202.1326 using in silico tools and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the absence of a commercial standard, synthetic N1-acetylisoputreanine was generated using enzymatic and chemical syntheses, and LC-MS/MS was used to confirm the structure of MF 202.1326 as N1-acetylisoputreanine, a proposed terminal polyamine catabolite that had not been previously detected in biological samples. Further analysis demonstrated that N1-acetylisoputreanine and an alternative form of this metabolite, N1-acetylisoputreanine-γ-lactam, are both present in human urine and are likely end-products of polyamine metabolism.

Original languageEnglish (US)
Pages (from-to)3921-3930
Number of pages10
JournalACS Omega
Volume2
Issue number7
DOIs
StatePublished - Jul 31 2017

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering

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