Estimating relative changes of metabolic fluxes.

Journal Article

Fluxes are the central trait of metabolism and Kinetic Flux Profiling (KFP) is an effective method of measuring them. To generalize its applicability, we present an extension of the method that estimates the relative changes of fluxes using only relative quantitation of 13C-labeled metabolites. Such features are directly tailored to the more common experiment that performs only relative quantitation and compares fluxes between two conditions. We call our extension rKFP. Moreover, we examine the effects of common missing data and common modeling assumptions on (r)KFP, and provide practical suggestions. We also investigate the selection of measuring times for (r)KFP and provide a simple recipe. We then apply rKFP to 13C-labeled glucose time series data collected from cells under normal and glucose-deprived conditions, estimating the relative flux changes of glycolysis and its branching pathways. We identify an adaptive response in which de novo serine biosynthesis is compromised to maintain the glycolytic flux backbone. Together, these results greatly expand the capabilities of KFP and are suitable for broad biological applications.

Full Text

Duke Authors

Cited Authors

  • Huang, L; Kim, D; Liu, X; Myers, CR; Locasale, JW

Published Date

  • November 20, 2014

Published In

Volume / Issue

  • 10 / 11

Start / End Page

  • e1003958 -

PubMed ID

  • 25412287

Electronic International Standard Serial Number (EISSN)

  • 1553-7358

International Standard Serial Number (ISSN)

  • 1553-734X

Digital Object Identifier (DOI)

  • 10.1371/journal.pcbi.1003958

Language

  • eng