Regular Article
Cytochrome P4503A-Dependent Metabolism of Tocopherols and Inhibition by Sesamin,☆☆

https://doi.org/10.1006/bbrc.2000.3706Get rights and content
Under a Creative Commons license
open archive

Abstract

Carboxychroman metabolites of the major dietary tocopherols are excreted in human urine, but the mechanism of their synthesis is unknown. We employed well-characterized inhibitors of specific cytochrome P-450 (CYP) enzymes to determine which form was likely involved in tocopherol side chain oxidation. Ketoconozole (1.0 μM), a potent and selective inhibitor of CYP3A, substantially inhibited metabolism of γ- and α-tocopherol in rat primary hepatocytes, and metabolism of γ- and δ-tocopherol in HepG2/C3A cells. Sulphaphenazole and cyclosporin, inhibitors of CYP2C and CYP27, respectively, were without effect. Sesamin, a sesame lignan that causes elevation of tissue tocopherol concentration in rats, strongly inhibited tocopherol metabolism by HepG2/C3A cells at 1.0 μM. These results support a CYP3A-dependent mechanism of side chain metabolism of tocopherols to water-soluble carboxychromans, and provide the first evidence of a specific enzyme involved in vitamin E metabolism. The data further suggest that sesamin increases tissue tocopherol concentration by inhibiting tocopherol catabolism.

Keywords

tocopherols
metabolism
cytochrome P450
carboxychroman
sesame
sesamin
ketoconozole

Cited by (0)

Support provided by USDA/NRI and NIH Training Grant DK07158-25 (T.J.S.).

☆☆

Support provided by USDA/NRI and NIH Training Grant DK07158-25 (T.J.S.).

1

To whom correspondence should be addressed. Fax: (607) 255-1033. E-mail: [email protected].