title: The extended catalysis of glutathione transferase.
abstract: Glutathione transferase reaches 0.5-0.8 mM concentration in the cell so it works in vivo under the unusual conditions of, [S]≪[E]. As glutathione transferase lowers the pK(a) of glutathione (GSH) bound to the active site, it increases the cytosolic concentration of deprotonated GSH about five times and speeds its conjugation with toxic compounds that are non-typical substrates of this enzyme. This acceleration becomes more efficient in case of GSH depletion and/or cell acidification. Interestingly, the enzymatic conjugation of GSH to these toxic compounds does not require the assumption of a substrate-enzyme complex; it can be explained by a simple bimolecular collision between enzyme and substrate. Even with typical substrates, the astonishing concentration of glutathione transferase present in hepatocytes, causes an unusual "inverted" kinetics whereby the classical trends of v versus E and v versus S are reversed.
authors.affiliation: Department of Chemical Sciences and Technologies, University of Rome, Tor Vergata, Rome, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Fabrini
authors.forename: Alessio
authors.initials: A
authors.lastname: Bocedi
authors.forename: Kutayba F
authors.initials: KF
authors.lastname: Dawood
authors.forename: Paola
authors.initials: P
authors.lastname: Turella
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Stella
authors.forename: Michael W
authors.initials: MW
authors.lastname: Parker
authors.forename: Jens Z
authors.initials: JZ
authors.lastname: Pedersen
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
authors.forename: Giovanni
authors.initials: G
authors.lastname: Antonini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ricci
mesh_terms: D055162:Biocatalysis; D004220:Disulfides / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007461:Iodoacetates; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008962:Models, Theoretical; D013379:Substrate Specificity
chemical_list: D004220:Disulfides; D007461:Iodoacetates; D007527:Isoenzymes; C484555:GSTA1 protein, human; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; D005978:Glutathione