Metabolic modeling of converging metabolic pathways: Analysis of non-steady state stable isotope-resolve metabolism of UDP-GlcNAc and UDP-GalNAc

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

3 Scopus citations

Abstract

We have developed a novel metabolic modeling methodology that traces the flow of functional moieties (chemical substructures) through metabolic pathways via the deconvolution of mass isotopologue data of specific metabolites. We have implemented a general simulated annealing/genetic algorithm for parameter optimization called Genetic Algorithm for Isotopologues in Metabolic Systems (GAIMS), with a model selection method developed from the Akaike information criterion. GAIMS is tailored for analysis of ultrahigh resolution, high mass-accuracy isotopologue data from Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR-MS) for interpretation of non-steady state stable isotope-resolved metabolomics (SIRM) experiments. We applied GAIMS to a time-course of uridine diphospho-N-acetylglucosamine (UDP-GlcNAc) and uridine diphospho-N-acetylgalactosamine (UDP-GalNAc) isotopologue data obtained from LNCaP-LN3 prostate cancer cells grown in [U-13C]-glucose. The best metabolic model was identified, which revealed the relative contribution of specific metabolic pathways to 13C incorporation from glucose into individual functional moieties of UDP-GlcNAc and UDP-GalNAc. Furthermore, this analysis allows direct comparison of MS isotopologue data with NMR positional isotopomer data for independent experimental cross-verification.

Original languageEnglish
Title of host publicationBIOINFORMATICS 2011 - Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms
Pages108-115
Number of pages8
StatePublished - 2011
EventInternational Conference on Bioinformatics Models, Methods and Algorithms, BIOINFORMATICS 2011 - Rome, Italy
Duration: Jan 26 2011Jan 29 2011

Publication series

NameBIOINFORMATICS 2011 - Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms

Conference

ConferenceInternational Conference on Bioinformatics Models, Methods and Algorithms, BIOINFORMATICS 2011
Country/TerritoryItaly
CityRome
Period1/26/111/29/11

Keywords

  • GAIMS
  • Mass spectrometry
  • Metabolic modelling
  • Model optimization
  • Model selection
  • Non-steady state
  • SIRM
  • Stable isotope-resolved metabolomics
  • Systems biochemistry
  • UDP-GalNAc
  • UDP-GlcNAc

ASJC Scopus subject areas

  • Information Systems
  • Applied Mathematics

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