Metabolite and isotopomer balancing in the analysis of metabolic cycles: II. Applications.

TitleMetabolite and isotopomer balancing in the analysis of metabolic cycles: II. Applications.
Publication TypeJournal Article
Year of Publication1999
AuthorsPark, SM, Klapa, MI, Sinskey, AJ, Stephanopoulos, G
JournalBiotechnol Bioeng
Date Published1999 Feb 20
KeywordsAcetic Acid, Acetone, Animals, Biotechnology, Carbon Isotopes, Citrate (si)-Synthase, Citric Acid Cycle, Escherichia coli, Gas Chromatography-Mass Spectrometry, Glyoxylates, Magnetic Resonance Spectroscopy, Mammals, Propionates, Pseudomonas, Pyruvate Carboxylase, Pyruvic Acid

In a previous paper (Klapa et al., 1999), we presented a model for the analysis of isotopomer distributions of the TCA cycle intermediates resulting from 13C (or 14C) labeling experiments. Results allow the rigorous determination of the degree of enrichment at specific carbon atoms of metabolites, of the molecular weight distribution of metabolite isotopomers, as well as of the fine structure of NMR spectra in terms of a small number of metabolic fluxes. In this paper we validate the model by comparing model predictions with experimental data and then apply it to the analysis of metabolic networks that have been investigated in previous studies. The results have allowed us to conclude that: (1) there is no evidence of propionyl-CoA carboxylase pathway in Escherichia coli; and (2) the possibility that acetone utilization in mammals occurs solely via the "lactate/methylglyoxal" pathway is consistent with available labeling data. The presented modeling framework provides additional constraints that must be satisfied by experimental data in a biochemical network structure and therefore enhances the power of labeling methods for resolving in vivo metabolic fluxes.

Alternate JournalBiotechnol Bioeng
Citation Key129
PubMed ID9921151