Simplifying metabolic complexity.

TitleSimplifying metabolic complexity.
Publication TypeJournal Article
Year of Publication2002
AuthorsBrand, MD, R Curtis, K
JournalBiochem Soc Trans
Volume30
Issue2
Pagination25-30
Date Published2002 Apr
ISSN0300-5127
KeywordsAdenosine Triphosphate, Animals, Gene Expression Regulation, Hepatocytes, Metabolism, Mitochondria, Models, Biological, Signal Transduction
Abstract

A complete description of the regulation of metabolism in even a single cell will be very hard to achieve, enormous and indigestible. However, there are two powerful ways to simplify the complexity. Firstly, related processes and intermediates can be grouped into a small number of modules, and the regulation of the simplified system can be studied. Secondly, control analysis can be used. With these simplifications to illuminate the important regulatory features, even a full description could be made intellectually and experimentally accessible without distorting the essential regulatory features. Modular control analysis is powerful because it can quantify the relative importance of different flows of regulatory information through any metabolic, physiological, signalling or transcriptional network. It can answer global questions about the importance of different pathways mediating any change to a system. It has been used to analyse how cadmium, a poison with multiple effects, changes oxidative phosphorylation in isolated mitochondria, and to quantify the regulation of energy metabolism in hepatocytes. It has been used to measure how energy metabolism is regulated during mitogen stimulation of thymocytes, quantifying the relative importance of different signalling pathways and how each pathway contributes to the activation of energy metabolism. Recently, we have applied modular control analysis to modern DNA microarray expression profiling to measure the importance of different groups of mRNA transcripts in mediating physiological responses.

DOI10.1042/0300-5127:0300025
Alternate JournalBiochem. Soc. Trans.
Citation Key10.1042/0300-5127:0300025
PubMed ID12023818