Subtleties in control by metabolic channelling and enzyme organization

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dc.contributor.authorKholodenko B.N.
dc.contributor.authorRohwer J.M.
dc.contributor.authorCascante M.
dc.contributor.authorWesterhoff H.V.
dc.date.accessioned2011-05-15T16:00:01Z
dc.date.available2011-05-15T16:00:01Z
dc.date.issued1998
dc.description.abstractBecause of its importance to cell function, the free-energy metabolism of the living cell is subtly and homeostatically controlled. Metabolic control analysis enables a quantitative determination of what controls the relevant fluxes. However, the original metabolic control analysis was developed for idealized metabolic systems, which were assumed to lack enzyme-enzyme association and direct metabolite transfer between enzymes (channelling). We here review the recently developed molecular control analysis, which makes it possible to study non-ideal (channelled, organized) systems quantitatively in terms of what controls the fluxes, concentrations, and transit times. We show that in real, non-ideal pathways, the central control laws, such as the summation theorem for flux control, are richer than in ideal systems: the sum of the control of the enzymes participating in a non-ideal pathway may well exceed one (the number expected in the ideal pathways), but may also drop to values below one. Precise expressions indicate how total control is determined by non-ideal phenomena such as ternary complex formation (two enzymes, one metabolite), and enzyme sequestration. The bacterial phosphotransferase system (PTS), which catalyses the uptake and concomitant phosphorylation of glucose (and also regulates catabolite repression) is analyzed as an experimental example of a non-ideal pathway. Here, the phosphoryl group is channelled between enzymes, which could increase the sum of the enzyme control coefficients to two, whereas the formation of ternary complexes could decrease the sum of the enzyme control coefficients to below one. Experimental studies have recently confirmed this identification, as well as theoretically predicted values for the total control. Macromolecular crowding was shown to be a major candidate for the factor that modulates the non-ideal behaviour of the PTS pathway and the sum of the enzyme control coefficients.
dc.description.versionArticle
dc.identifier.citationMolecular and Cellular Biochemistry
dc.identifier.citation184
dc.identifier.citation02-Jan
dc.identifier.issn3008177
dc.identifier.urihttp://hdl.handle.net/10019.1/11481
dc.subjectenzyme
dc.subjectglucose
dc.subjectphosphotransferase
dc.subjectarticle
dc.subjectbacterial membrane
dc.subjectcell function
dc.subjectenergy metabolism
dc.subjectenzyme activity
dc.subjectenzyme phosphorylation
dc.subjectkinetics
dc.subjectmacromolecule
dc.subjectmetabolic regulation
dc.subjectnonhuman
dc.subjectreaction analysis
dc.subjectthermodynamics
dc.subjectEnergy Metabolism
dc.subjectEscherichia coli
dc.subjectGlucose
dc.subjectHomeostasis
dc.subjectKinetics
dc.subjectPhosphoenolpyruvate Sugar Phosphotransferase System
dc.subjectPhosphorylation
dc.subjectSubstrate Cycling
dc.subjectThermodynamics
dc.subjectBacteria (microorganisms)
dc.titleSubtleties in control by metabolic channelling and enzyme organization
dc.typeArticle
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