title: Gamma-tocotrienol and gamma-tocopherol are primarily metabolized to conjugated 2-(beta-carboxyethyl)-6-hydroxy-2,7,8-trimethylchroman and sulfated long-chain carboxychromanols in rats.
abstract: The metabolism of gamma-tocotrienol (gamma-TE) and gamma-tocopherol (gamma-T) was investigated in human A549 cells and in rats. Similar to gamma-T, A549 cells metabolized gamma-TE to sulfated 9'-, 11'-, and 13'-carboxychromanol and their unconjugated counterparts. After 72-h incubation with the cells, 90% of long-chain carboxychromanols in the culture media from gamma-TE, but <45% from gamma-T, were in the sulfated form. The formation of these metabolites was further investigated in rats gavaged by gamma-TE at 10 or 50 mg/kg, gamma-T at 10 mg/kg, or tocopherol-stripped corn oil in controls. Six hours after a single dosing, the supplemented rats had increased plasma concentrations of 13'-carboxychromanol and sulfated 9'-, 11'-, 13'-carboxychromanol, whereas none of these metabolites were detectable in the controls. Sulfated 11'-carboxychromanol was the most abundant long-chain metabolite in gamma-TE-supplemented rats. Sulfatase/glucuronidase hydrolysis revealed for the first time that >88% 2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), the terminal beta-oxidation metabolite, was in the conjugated form in the plasma. In all groups, conjugated gamma-CEHC accounted for >75% of total metabolites, whereas free CEHC was a minor metabolite. At 10 mg/kg, the plasma concentrations of total metabolites from gamma-TE-supplemented rats were higher (P < 0.05) than those from gamma-T-fed rats. These results demonstrate that in rats, conjugation such as sulfation occurs parallel to beta-oxidation in the liver and is quantitatively important to vitamin E metabolism. Conjugated long-chain carboxychromanols may be novel excreted metabolites during supplementation. Our data also provide in vivo evidence that gamma-TE is more extensively metabolized than gamma-T.
authors.affiliation: Department of Foods and Nutrition, Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Helene
authors.initials: H
authors.lastname: Freiser
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002460:Cell Line; D002839:Chromans / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D011650:Pulmonary Alveoli; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000378:metabolism*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D024504:gamma-Tocopherol / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D002839:Chromans; D013431:Sulfates; D014810:Vitamin E; C013649:plastochromanol 8; D024504:gamma-Tocopherol