Enzymatic formation and electrochemical characterization of multiply substituted glutathione conjugates of hydroquinone.
1,4-Benzoquinone can undergo redox cycling in the presence of glutathione to produce multiply substituted products. It has previously been shown that the nephrotoxicity of the hydroquinone-glutathione conjugates increases with increasing substitution. However, based on chromatographically-assisted hydrodynamic voltammetry (CA-HDV), the oxidation potential was shown to apparently increase which, should lead to decreased toxicity. From the chemical formation of multiply substituted hydroquinone-glutathione conjugates from benzoquinone and glutathione, it is clear that the thermodynamic oxidation potential must decrease as substitution increases. This was confirmed by cyclic voltammetric (CV) characterization of the isolated conjugates. The discrepancy between the CV and CA-HDV data apparently results from kinetic factors arising from differences in the treatment of the electrode surface between the two experiments. The multiply substituted hydroquinone-glutathione conjugates were also produced in horseradish peroxidase incubations containing hydroquinone and glutathione. These products were identified chromatographically, spectrophotometrically, and electrochemically. The increasing ease of oxidation and the possible enzymatic formation of multiply substituted hydroquinone-glutathione conjugates indicates that this pathway may occur in vivo and contribute to the toxicity of quinones.
Puckett-Vaughn
D L
DL
Department of Chemistry, University of Kansas, Lawrence 66045.
Stenken
J A
JA
Scott
D O
DO
Lunte
S M
SM
Lunte
C E
CE
D002853:Chromatography, Liquid; D004563:Electrochemistry; D005978:Glutathione / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000378:metabolism; D006873:Hydroquinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet
D006873:Hydroquinones; D006735:Horseradish Peroxidase; D005978:Glutathione; C031927:hydroquinone