title: Modeling the role of negative cooperativity in metabolic regulation and homeostasis.
abstract: 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.
authors.affiliation: Department of Biology, Harvey Mudd College, Claremont, California, United States of America. eliot.bush@hmc.edu
authors.forename: Eliot C
authors.initials: EC
authors.lastname: Bush
authors.forename: Anne E
authors.initials: AE
authors.lastname: Clark
authors.forename: Chris M
authors.initials: CM
authors.lastname: DeBoever
authors.forename: Lillian E
authors.initials: LE
authors.lastname: Haynes
authors.forename: Sidra
authors.initials: S
authors.lastname: Hussain
authors.forename: Singer
authors.initials: S
authors.lastname: Ma
authors.forename: Matthew B A
authors.initials: MB
authors.lastname: McDermott
authors.forename: Matthew M
authors.initials: MM
authors.lastname: McDermott
authors.forename: Adam M
authors.initials: AM
authors.lastname: Novak
authors.forename: John S
authors.initials: JS
authors.lastname: Wentworth
mesh_terms: D004791:Enzyme Inhibitors / Q000494:pharmacology; D004798:Enzymes / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008024:Ligands; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008954:Models, Biological; D011485:Protein Binding
chemical_list: D004791:Enzyme Inhibitors; D004798:Enzymes; D008024:Ligands