Regioselectivity and reversibility of the glutathione conjugation of quercetin quinone methide.
The chemical reactivity, isomerization, and glutathione conjugation of quercetin o-quinone were investigated. Tyrosinase was used to generate the unstable quercetin o-quinone derivative which could be observed upon its subsequent scavenging by glutathione. Identification of the products revealed formation of 6-glutathionyl-quercetin and 8-glutathionyl-quercetin adducts. Thus, in particular, glutathione adducts in the A ring of quercetin were formed, a result which was not expected a priori. Quantum mechanical calculations support the possibility that the formation of these glutathione adducts can be explained by an isomerization of quercetin o-quinone to p-quinone methides. Surprisingly, additional experiments of this study reveal the adduct formation to be reversible, leading to interconversion between the two quercetin glutathione adducts and possibilities for release and further electrophilic reactions of the quercetin quinone methide at cellular sites different from those of its generation.
Boersma
M G
MG
Laboratories of Biochemistry and Toxicology, Wageningen University, Dreijenlaan 3, 6703 HA, and Tuinlaan 5, 6703 HE Wageningen, The Netherlands.
Vervoort
J
J
Szymusiak
H
H
Lemanska
K
K
Tyrakowska
B
B
Cenas
N
N
Segura-Aguilar
J
J
Rietjens
I M
IM
D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000378:metabolism*; D045563:Indolequinones; D007211:Indoles / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D011794:Quercetin / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D045563:Indolequinones; D007211:Indoles; D011809:Quinones; C068040:quinone methide; D011794:Quercetin; D005978:Glutathione