1-Chloro-2,4-dinitrobenzene-mediated irreversible inactivation of acidic glutathione S-transferases. Inactivation mechanism--a saturation-type or simple second-order kinetic process?
A critical analysis of the inactivation kinetics exhibited by the acidic human glutathione S-transferase (GST) enzymes is presented. Data on the 1-chloro-2,4-dinitrobenzene (CDNB)-facilitated inactivation of human placental GST pi have been utilized in conjunction with published inactivation data from the literature to answer the following two questions: (a) do the inactivation kinetics deviate significantly from a simple pseudo first-order model? (b) What is the kinetic mechanism of irreversible electrophilic co-substrate-mediated inactivation of human acidic GSTs? Inactivation of human placental GST pi in the presence of 7-aminocephalosporanic acid, a non-electrophilic non-substrate ligand, is characterized and shown to occur via a process analogous to the second mechanism proposed for CDNB inactivation of the enzyme, namely: pH- and [ligand]-independent solvational inactivation.
Adams
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Department of Chemical Pathology, University of Cape Town, Republic of South Africa.
Sikakana
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D002511:Cephalosporins / Q000494:pharmacology; D004137:Dinitrochlorobenzene / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010920:Placenta / Q000201:enzymology*
D002511:Cephalosporins; D004137:Dinitrochlorobenzene; C030735:7-aminocephalosporanic acid; D005982:Glutathione Transferase