Reductive addition of glutathione to p-benzoquinone, 2-hydroxy-p-benzoquinone, and p-benzoquinone epoxides. Effect of the hydroxy- and glutathionyl substituents on p-benzohydroquinone autoxidation.
The reductive addition of GSH to p-benzoquinones, 2-hydroxy-p-benzoquinone, and 2,3-epoxy-p-benzoquinones with different degree of methyl substitution was studied in terms of absorption spectral changes and autoxidation reactions. The nucleophilic addition of GSH to p-benzoquinone yields a glutathionyl-p-benzohydroquinone product with maximal absorption at lambda 303nm. This compound autoxidizes slowly--but at a rate 8-fold higher than the parent hydroquinone--to glutathionyl-p-benzoquinone, which reveals maximal absorption at lambda 367 nm. The autoxidation of the glutathionyl derivative is accompanied by O2 consumption and H2O2 formation. The nucleophilic addition of GSH to either 2-hydroxy-p-benzoquinone or 2,3-epoxy-p-benzoquinone yields the same primary molecular product, 2-hydroxy-5-glutathionyl-p-benzohydroquinone, a compound that shows maximal absorption at lambda 300 nm and autoxidizes at rates substantially higher (44-fold) than the parent glutathionyl hydroquinone lacking a -OH substituent. The autoxidation product, 2-hydroxy-5-glutathionyl-p-benzoquinone, reveals maximal absorbance at lambda 343 nm as well as a resolved absorption band at longer wavelengths (lambda 520 nm), the latter contributed by the -OH substituent. The glutathionyl substituent exerted only minor changes in the reduction potential of the quinones, whereas the -OH substituent lowered significantly the half-wave reduction potential, as measured in aqueous solutions. The rate of autoxidation was markedly enhanced by both substituents as follows: hydroxy-glutathionyl-p-benzohydroquinone much greater than hydroxy-p-benzohydroquinone much greater than glutathionyl-p-benzohydroquinone greater than p-benzohydroquinone. Superoxide dismutase enhanced the rate of autoxidation of p-benzohydroquinone and its glutathionyl adduct, whereas it inhibited autoxidation of the hydroxy derivatives with or without glutathionyl substitution. The biochemical significance of these results is discussed in terms of the pro-oxidant character of the reductive addition of GSH to p-benzoquinones, alpha-hydroxyquinones, and quinone epoxides.
Brunmark
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Department of Pathology II, University of Linköping, Sweden.
Cadenas
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D016227:Benzoquinones; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione; D007700:Kinetics; D010084:Oxidation-Reduction; D011809:Quinones; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
D016227:Benzoquinones; D011809:Quinones; C054094:2,3-epoxy-1,4-benzoquinone; C004532:quinone; C054093:2-hydroxy-1,4-benzoquinone; D005978:Glutathione