title: Hepatic biotransformation of alkylresorcinols is mediated via cytochrome P450 and β-oxidation: a proof of concept study.
abstract: Alkylresorcinols (AR) are phenolic lipids present in the bran of some cereals. AR may serve as a biomarker for whole grain wheat and rye intake. While AR pharmacokinetics and two major metabolites have been reported, the metabolic pathways contributing to their relatively rapid elimination from the circulation remain to be speculative. In this study, we investigated if ω- and β-oxidation mediate catabolism of the AR homologue C19:0 to form 3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), using 3 in vitro platforms, human cytochrome P450 4F2 (CYP4F2), human liver S9, and HepG2 cells. One hydroxylated C19:0 metabolite was formed by CYP4F2 and one hydroxylated and one carboxylated C19:0 were tentatively identified after incubation of AR with S9. The formation of DHPPA was quantifiable when HepG2 cells were treated with C19:0 for 48 h. Our results are consistent with a metabolic pathway by which AR are degraded to phenolic acids via CYP4F2-mediated ω-oxidation and subsequent β-oxidation.
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111, USA.
authors.forename: Matti
authors.initials: M
authors.lastname: Marklund
authors.forename: Nicola M
authors.initials: NM
authors.lastname: McKeown
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Blumberg
authors.forename: C-Y Oliver
authors.initials: CY
authors.lastname: Chen
mesh_terms: D001711:Biotransformation; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000072470:Cytochrome P450 Family 4; D006801:Humans; D062385:Hydroxybenzoates / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010666:Phenylpropionates / Q000378:metabolism; D012118:Resorcinols / Q000378:metabolism*
chemical_list: C532605:3-(3,5-dihydroxyphenyl)-1-propanoic acid; D062385:Hydroxybenzoates; D010666:Phenylpropionates; D012118:Resorcinols; C076950:alpha-resorcylic acid; D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human