Modeling the role of negative cooperativity in metabolic regulation and homeostasis

A significant proportion of enzymes display cooperativity in binding ligand molecules, and such effects have an important impact on metabolic regulation. This is easiest to understand in the case of positive cooperativity. Sharp responses to changes in metabolite concentrations can allow organisms t...

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Bibliographic Details
Published in:	PloS one Vol. 7; no. 11; p. e48920
Main Authors:	Bush, Eliot C, Clark, Anne E, DeBoever, Chris M, Haynes, Lillian E, Hussain, Sidra, Ma, Singer, McDermott, Matthew B A, McDermott, Matthew M, Novak, Adam M, Wentworth, John S
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 09-11-2012 Public Library of Science (PLoS)
Subjects:	Analysis Binding Biochemistry Biology Computer applications Computer Science Cooperativity Design optimization Environmental changes Enzyme Inhibitors - pharmacology Enzymes Enzymes - metabolism Homeostasis Homeostasis - drug effects Homeostasis - physiology Kinetics Ligands Mathematical models Medicine Metabolic Networks and Pathways - drug effects Metabolism Metabolites Models, Biological Molecular biology Protein Binding Regulation United States > US California
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Summary:	A significant proportion of enzymes display cooperativity in binding ligand molecules, and such effects have an important impact on metabolic regulation. This is easiest to understand in the case of positive cooperativity. Sharp responses to changes in metabolite concentrations can allow organisms to better respond to environmental changes and maintain metabolic homeostasis. However, despite the fact that negative cooperativity is almost as common as positive, it has been harder to imagine what advantages it provides. Here we use computational models to explore the utility of negative cooperativity in one particular context: that of an inhibitor binding to an enzyme. We identify several factors which may contribute, and show that acting together they can make negative cooperativity advantageous.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: EB. Performed the experiments: EB AC CD LH SH SM MM AN JW. Analyzed the data: EB SH. Wrote the paper: EB.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0048920