|Chen, C-y oliver|
Submitted to: Food Chemistry
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/31/2013
Publication Date: 8/15/2013
Citation: Marklund, M., Mckeown, N.M., Blumberg, J.B., Chen, C. 2013. Hepatic biotransformation of alkylresorcinols is mediated via cytochrome P450 and beta-oxidation: a proof of concept study. Food Chemistry. 139:925-930. Interpretive Summary: Alkylresorcinols (AR) are lipid-like compounds abundant in the bran of wheat and rye kernels. They are present in whole grain and bran foods of these cereals but absent or found at very low concentrations in refined cereal foods. AR have been utilized as a marker of whole grain wheat and rye intake in different populations. While AR absorption and elimination and two major metabolites have been studied and reported on, the metabolic pathways contributing to their relatively rapid elimination from circulation in the body have not been identified. We investigated the metabolic reaction of a key AR compound to form two simple phenolic acid breakdown products using three different approaches. Using material derived from humans, we tested AR metabolism with a pure enzyme, an extract of liver (where most AR metabolism occurs), and cultured liver cells. We identified two unique intermediary breakdown products that suggest AR are degraded via the metabolic pathway of a specific cytochrome enzyme (CYP4F2). These data will help inform the design of new human studies examining the role of whole grain foods in the improvement and maintenance of health.
Technical 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 whether omega- and beta-oxidation mediate catabolism of the AR homolog C19:0 to form 3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA) using 3 in vitro platforms, including 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 were treated with C19:0 for 48 h. Our results are consistent with a metabolic pathway where AR are degraded to short-chained phenolic acids via CYP4F2-mediated omega-oxidation and subsequent beta-oxidation.