New metabolic pathways for flavanones catalyzed by rat liver microsomes.
Flavonoids represent a diverse group of natural pigments widely distributed in the plant kingdom and are an important component of human diet due to their high content in fruits and vegetables. Since many flavonoids have been shown to be potent inhibitors, substrates, and even inducers of various cytochrome P450 isoforms, there is considerable interest in studying interactions of this class of molecules with the cytochrome P450 enzyme system. In this study, the metabolism of several simple flavanones by rat liver microsomes was investigated and compared. In addition to the expected aromatic hydroxylation products, several novel metabolic pathways were observed including C-ring desaturation to form the corresponding flavones, oxidation of the B-ring to generate an unusual quinol oxidation product, B-ring cleavage with the formation of chromone derivatives, and reduction of carbonyl group to form flavan-4-ol derivatives. The metabolites were characterized and identified primarily by using liquid chromatographytandem mass spectrometry with comparison to authentic standards. Formation of flavones from dietary flavanones might have biological significance since flavones often exhibit pharmacological activities that are different from those of flavanones. However, little is known about the pharmacological activities of the other types of flavonone metabolites.
Nikolic
Dejan
D
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612-7231, USA.
van Breemen
Richard B
RB
D000818:Animals; D001711:Biotransformation / Q000187:drug effects / Q000502:physiology*; D002853:Chromatography, Liquid / Q000379:methods; D044950:Flavanones / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013058:Mass Spectrometry / Q000379:methods; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D015394:Molecular Structure; D011809:Quinones / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats
D044950:Flavanones; D011809:Quinones; C005273:naringenin; C083152:liquiritigenin