The extended catalysis of glutathione transferase

• Published in: FEBS letters Vol. 585; no. 2; pp. 341 - 345
• Main Authors: Fabrini, Raffaele, Bocedi, Alessio, Dawood, Kutayba F., Turella, Paola, Stella, Lorenzo, Parker, Michael W., Pedersen, Jens Z., Federici, Giorgio, Antonini, Giovanni, Ricci, Giorgio
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 21.01.2011
• Subjects: 1-choro-2,4-dinitrobenzene; 2,2′-dithionitrobenzoic acid; 2-thionitrobenzoate; acidification; active sites; Biocatalysis; bovine serum albumin; BSA; catalytic activity; CDNB; chemical concentration; Detoxification; Disulfides - metabolism; dithiodiethanol; DTNB; DTOH; enzyme substrates; Glutathione; Glutathione - metabolism; Glutathione transferase; Glutathione Transferase - metabolism; GSH; GST; hepatocytes; Humans; IAA; Inverted kinetics; Iodoacetates; iodoacetic acid; Isoenzymes - metabolism; Kinetics; Kinetics simulation; Liver - enzymology; Models, Theoretical; Non-typical GST substrate; Substrate Specificity; TNB; toxicity; DTNB; Detoxification; IAA; GST; TNB; DTOH; CDNB; BSA; Non-typical GST substrate; Kinetics simulation; Glutathione transferase; GSH; Inverted kinetics; Glutathione
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2010.12.009

Glutathione transferase reaches 0.5–0.8mM concentration in the cell so it works in vivo under the unusual conditions of, [S]≪[E]. As glutathione transferase lowers the pKa 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.