Metabolite and isotopomer balancing in the analysis of metabolic cycles: I. Theory.

Abstract:

:Proper analysis of label distribution in metabolic pathway intermediates is critical for correct interpretation of experimental data and strategic experimental design. While, for example, 13C nuclear magnetic resonance (NMR) spectroscopy is usually limited to the measurement of degrees of 13C enrichment, more information about metabolic fluxes can be extracted from the fine structure of NMR spectra, or molecular weight distributions of isotopomers of metabolic intermediates (measured by gas chromatography-mass spectrometry). For this purpose, rigorous accounting for the contribution of all pathways to label distribution is required, especially contributions resulting from multiple turns of metabolic cycles. In this paper we present a mathematical model developed to analyze isotopomer distributions of tricarboxylic acid cycle (TCA) intermediates following the administration of 13C (or 14C) labeled substrates. The theory presented provides the basis to analyze 13C NMR spectra and molecular weight distributions of metabolites. In a companion paper (Park et al., 1999), the theory is applied to the analysis of several cases of biological significance. Copyright 1999 John Wiley & Sons, Inc.

journal_name

Biotechnol Bioeng

authors

Klapa MI,Park SM,Sinskey AJ,Stephanopoulos G

doi

10.1002/(sici)1097-0290(19990220)62:4<375::aid-bit

subject

Has Abstract

pub_date

1999-02-01 00:00:00

pages

375-391

issue

4

eissn

0006-3592

issn

1097-0290

pii

10.1002/(SICI)1097-0290(19990220)62:4<375::AID-BIT

journal_volume

62

pub_type

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