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.

Fabrini, R., Bocedi, A., Dawood, K., Turella, P., Stella, L., Parker, M., et al. (2011). The extended catalysis of glutathione transferase. FEBS LETTERS, 585(2), 341-345 [10.1016/j.febslet.2010.12.009].

The extended catalysis of glutathione transferase

Bocedi, A;STELLA, LORENZO;PEDERSEN, JENS ZACHO;FEDERICI, GIORGIO;RICCI, GIORGIO
2011-01-21

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.
21-gen-2011
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/10 - BIOCHIMICA
Settore CHIM/02 - CHIMICA FISICA
English
Con Impact Factor ISI
Models, Theoretical; Kinetics; Isoenzymes; Iodoacetates; Substrate Specificity; Liver; Disulfides; Glutathione; Glutathione Transferase; Biocatalysis; Humans
Fabrini, R., Bocedi, A., Dawood, K., Turella, P., Stella, L., Parker, M., et al. (2011). The extended catalysis of glutathione transferase. FEBS LETTERS, 585(2), 341-345 [10.1016/j.febslet.2010.12.009].
Fabrini, R; Bocedi, A; Dawood, K; Turella, P; Stella, L; Parker, M; Pedersen, Jz; Federici, G; Antonini, G; Ricci, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/11624
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