Covalent Binding of the Flavonoid Quercetin to Human Serum Albumin

Abstract

Quercetin is an abundant flavonoid in the human diet with numerous biological activities, which may contribute to the prevention of human disease but also may be potentially harmful. Quercetin is oxidized in cells to products capable of covalently binding to cellular proteins, a process that may be important for its biological activities. In the present study, using radiolabeled drug and quantifying the products after electrophoretic separation, proteins to which oxidized quercetin is binding irreversibly were identified. The binding of quercetin to human serum albumin (HSA) in human blood and the effect of stimulation of neutrophilic myeloperoxidase on this binding were also measured. The in vitro binding of quercetin to eight proteins in the presence of catalytic amounts of horseradish peroxidase and hydrogen peroxide was highly selective for HSA. For all proteins the binding was dramatically decreased by reduced L-glutathione. In the blood samples, the release of neutrophilic myeloperoxidase by phorbol ester caused a 3-fold increase in the binding of quercetin to HSA. This study shows that quercetin in the presence of peroxidase/hydrogen peroxide covalently links to proteins with a particularly high affinity for HSA and that this also may occur in vivo after exposure to quercetin. This provides further insights into the complex behavior of this major dietary flavonoid.