Recent insights into oxidative metabolism of quercetin: catabolic profiles, degradation pathways, catalyzing metalloenzymes and molecular mechanisms

Quercetin is the most abundant polyphenolic flavonoid (flavonol subclass) in vegetal foods and medicinal plants. This dietary chemopreventive agent has drawn significant interest for its multiple beneficial health effects ("polypharmacology") largely associated with the well-documented antioxidant properties. However, controversies exist in the literature due to its dual anti-/pro-oxidant character, poor stability/bioavailability but multifaceted bioactivities, leaving much confusion as to its exact roles in vivo. Increasing evidence indicates that a prior oxidation of quercetin to generate an array of chemical diverse products with redox-active/electrophilic moieties is emerging as a new linkage to its versatile actions. The present review aims to provide a comprehensive overview of the oxidative conversion of quercetin by systematically analyzing the current quercetin-related knowledge, with a particular focus on the complete spectrum of metabolite products, the enzymes involved in the catabolism and the underlying molecular mechanisms. Herein we review and compare the oxidation pathways, protein structures and catalytic patterns of the related metalloenzymes (phenol oxidases, heme enzymes and specially quercetinases), aiming for a deeper mechanistic understanding of the unusual biotransformation behaviors of quercetin and its seemingly controversial biological functions.