Identification and quantitation of novel vitamin E metabolites, sulfated long-chain carboxychromanols, in human A549 cells and in rats

Qing Jiang, Helene Freiser, Karl V. Wood, and Xinmin Yin

Foods and Nutrition, Purdue University, West Lafayette, IN 47907

Corresponding Author: qjiang{at}purdue.edu

Metabolism of vitamin E involves oxidation of the phytyl chain to generate terminal metabolite CEHCs [(2-carboxyethyl)-hydroxychroman], via intermediate formation of 13’-hydroxychromanol and long-chain carboxychromanols. Conjugated (including sulfated) metabolites were previously reported, but were limited to CEHCs. Here, employing electrospray and inductively-coupled plasma mass spectrometry, we discovered that $gamma$ -tocopherol and $delta$ -tocopherol were metabolized to sulfated 9’-, 11’- and 13’-carboxychromanols in human A549 cells. To further study the metabolites, we developed a HPLC assay with fluorescent detection that simultaneously analyzes sulfated and non-conjugated intermediate metabolites. Using this assay, we found that sulfated metabolites were converted to non-conjugated carboxychromanols by sulfatase digestion. In cultured cells, approximately 45% long-chain carboxychromanols from $gamma$ -tocopherol but only 10% from $delta$ -tocopherol were sulfated. Upon supplementation with $gamma$ -tocopherol, rats had elevated tissue levels of sulfated 9’-, 11’- and 13’-carboxychromanols, 13’-hydroxychromanol, 13’-carboxychromanol and $gamma$ -CEHC. The plasma concentrations of combined sulfated long-chain metabolites were comparable to or exceeded those of CEHCs, and increased proportionally with the supplement dosages of $gamma$ -tocopherol. Our study identified sulfated long-chain carboxychromanols as novel vitamin E metabolites, and provided evidence that sulfation may occur parallel with $beta$ -oxidation. In addition, the HPLC-fluorescent assay is a useful tool for investigation of vitamin E metabolism.

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