Determination of the relative contributions of the diselenide and selenol forms of ebselen in the mechanism of its glutathione peroxidase-like activity.
The molecular basis of the glutathione peroxidase activity of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) was investigated by the use of synthesised, authentic intermediates identical to those formed by the reaction of ebselen with glutathione. The second order rate constants for the reaction of ebselen (0.29 mM-1 min-1), ebselen-glutathione selenosulfide (less than or equal to 0.01 mM-1 min-1), ebselen selenol (2.8 mM-1 min-1) and ebselen diselenide (0.32 mM-1 min-1) with hydrogen peroxide reveal that the selenol is particularly active in this respect. The determination of the relative amounts of ebselen selenol and diselenide under typical peroxidase assay conditions implies that the selenol is the predominant molecular species responsible for the glutathione--(70%)--and dithiothreitol--(96%)--dependent peroxidase activity of ebselen.
Morgenstern
R
R
Department of Toxicology, Karolinska Institute, Stockholm, Sweden.
Cotgreave
I A
IA
Engman
L
L
D000813:Anilides / Q000378:metabolism*; D001393:Azoles / Q000378:metabolism*; D001549:Benzamides / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D054833:Isoindoles; D007700:Kinetics; D016566:Organoselenium Compounds / Q000378:metabolism*; D012643:Selenium / Q000378:metabolism*; D018036:Selenium Compounds
D000813:Anilides; D001393:Azoles; D001549:Benzamides; D054833:Isoindoles; D016566:Organoselenium Compounds; D018036:Selenium Compounds; C067619:bis(2-(N-phenylcarboxamido)phenyl)diselenide; C075952:2-selenylbenzanilide; C042986:ebselen; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005978:Glutathione; D012643:Selenium; D004229:Dithiothreitol; C025698:selenium disulfide