The sum of the control coefficients of all enzymes on the flux through a group‐transfer pathway can be as high as two

Abstract

In simple metabolic pathways the control exerted by enzyme concentrations on the pathway flux adds up to one when the control is quantified in terms of control coefficients. In this paper we demonstrate that this classical summation theorem has to be modified in pathways where the enzymes participate by transferring a group between each other. We derive the corresponding new control theorem and show how it is consistent with standard metabolic control analysis. In grouptransfer pathways lacking enzyme complexes, the sum of the flux control by enzyme concentrations and by the donor and acceptor couples of the pathway, equals two. In group-transfer pathways with enzyme-enzyme interactions the flux control by the dissociation rate constants of the enzymeenzyme complexes must be added to obtain this sum of two. In all cases, the sum of the controls by all reaction activities remains one. Both by using the new theorem and by numerical simulations, we then demonstrate that, in group-transfer pathways with or without enzyme interactions, the sum of the control of enzymes on the pathway flux is higher than one and can reach a value of two, The total control of all enzymes on the concentration of any intermediate either with or without the transferred group can be equal to one, rather than to the zero found in the classical case. Examples of group-transfer pathways are the bacterial phosphoenolpyruvate : sugar phosphotransferase system, the main pathway for uptake of sugars in Enterobacteriaceae, and the electron-transfer chain in free-energy transducing membranes.

Distributed control for recruitment, scanning and subunit joining steps of translation initiation

“…A further key issue relates to the summation rule (35), which states that the sum of all control coefficients should equal 1. More recent results have indicated that this sum can in fact be >1 (approaching 2) for metabolic pathways if there is macromolecular crowding (38) or where the enzymes on a pathway exchange substrate groups (39). Our data now show that rate control summation in the translation initiation pathway, and therefore probably in other macromolecular assembly pathways, follows a different rule to that applicable to most metabolic pathways.…”

Gamma-glutamylcysteine synthetase and tryparedoxin 1 exert high control on the antioxidant system in Trypanosoma cruzi contributing to drug resistance and infectivity

“…The explanation is that, unlike canonical metabolic pathways, this is an electron-transfer pathway in which each individual redox reaction (process) compulsorily involves two enzymes, leading to a stoichiometry of one reaction/two enzymes (and second-order dependence reaction on enzyme concentration) instead of the usual one reaction/one enzyme (and first-order reaction dependence on enzyme concentration). Therefore, the sum of the enzymes’ flux control coefficients on the transfer of groups such as in redox pathways must be added to the sum of two, whilst the sum of the flux control coefficients on the whole process of peroxide reduction remains to be one (the pathway flux maintains a first-order dependence on enzyme activities) [43]. Kinetic modeling of the redox pathway reported here for the first time, allowed to obtain the C J ai on the peroxide reduction process, enabling to dissect C J ai values of 0.11–0.16 for TryR, 0.64–0.73 for TXN1 and 0.17–0.2 for TXNPx, respectively, considering that the sum of all C J ai must add up to 1.0.…”

Mitochondrial network energetics in the heart

“…When respiration was activated with substrates of the creatine kinase system (MgATP, creatine, although not with ADP), metabolic channeling happened as detected by flux control coefficients larger than one (96). Summation of flux control coefficients larger than one is expected under channeling of substrates through organized macromolecular complexes (97, 98) lending support, although indirect, to the existence of an MI.…”