Title
Quantitative analysis of flux regulation through hierarchical regulation analysis
Author
van Eunen, K.
Rossell, S.
Bouwman, J.
Westerhoff, H.V.
Bakker, B.M.
Centraal Instituut voor Voedingsonderzoek TNO
Publication year
2011
Abstract
Regulation analysis is a methodology that quantifies to what extent a change in the flux through a metabolic pathway is regulated by either gene expression or metabolism. Two extensions to regulation analysis were developed over the past years: (i) the regulation of Vmax can be dissected into the various levels of the gene-expression cascade, such as transcription, translation, protein degradation, etc. and (ii) a time-dependent version allows following flux regulation when cells adapt to changes in their environment. The methodology of the original form of regulation analysis as well as of the two extensions will be described in detail. In addition, we will show what is needed to apply regulation analysis in practice. Studies in which the different versions of regulation analysis were applied revealed that flux regulation was distributed over various processes and depended on time, enzyme, and condition of interest. In the case of the regulation of glycolysis in baker's yeast, it appeared, however, that cells that remain under respirofermentative conditions during a physiological challenge tend to invoke more gene-expression regulation, while a shift between respirofermentative and respiratory conditions invokes an important contribution of metabolic regulation. The complexity of the regulation observed in these studies raises the question what is the advantage of this highly distributed and condition-dependent flux regulation. © 2011 Elsevier Inc. All rights reserved.
Subject
Life
PHS - Pharmacokinetics & Human Studies
EELS - Earth, Environmental and Life Sciences
Nutrition Health
Gene expression regulation
Hierarchical regulation analysis
Metabolic regulation
Posttranscriptional regulation
Regulation analysis
To reference this document use:
http://resolver.tudelft.nl/uuid:297ba1e2-2dd6-4041-8408-4e424dbd71b5
DOI
https://doi.org/10.1016/b978-0-12-385118-5.00027-x
TNO identifier
435956
ISSN
0076-6879
Source
Methods in Enzymology, 500, 571-595
Document type
conference paper