title: Robustness in glyoxylate bypass regulation.
abstract: The glyoxylate bypass allows Escherichia coli to grow on carbon sources with only two carbons by bypassing the loss of carbons as CO(2) in the tricarboxylic acid cycle. The flux toward this bypass is regulated by the phosphorylation of the enzyme isocitrate dehydrogenase (IDH) by a bifunctional kinase-phosphatase called IDHKP. In this system, IDH activity has been found to be remarkably robust with respect to wide variations in the total IDH protein concentration. Here, we examine possible mechanisms to explain this robustness. Explanations in which IDHKP works simultaneously as a first-order kinase and as a zero-order phosphatase with a single IDH binding site are found to be inconsistent with robustness. Instead, we suggest a robust mechanism where both substrates bind the bifunctional enzyme to form a ternary complex.
authors.affiliation: Department of Molecular Cell Biology and Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel. guy.shinar@weizmann.ac.il
authors.forename: Guy
authors.initials: G
authors.lastname: Shinar
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rabinowitz
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
mesh_terms: D001665:Binding Sites; D004926:Escherichia coli / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D006038:Glyoxylates / Q000378:metabolism*; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation
chemical_list: D006038:Glyoxylates; D007521:Isocitrate Dehydrogenase; C031150:glyoxylic acid