carboxyethyl-hydroxychroman and 2-7-8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman

To elucidate the characteristics of γ-tocopherol metabolism, serum concentrations of α- and γ-tocopherol, and urinary excretion of their metabolites after ingestion of α- or γ-tocopherol, major isoforms in our diet, were compared. Six healthy Japanese women (age 22.7±1.7 y old, BMI 21.4±0.9) ingested 134 mg of α- or γ-tocopherol, and blood and urine were collected until 72 h later. After α-tocopherol intake, the serum concentration of α-tocopherol increased at 12-24 h, and urinary excretion of 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman (α-CEHC), an α-tocopherol metabolite, increased at 12-36 h. However, after γ-tocopherol intake, the serum concentration of γ-tocopherol increased at 6-12 h, and excretion of 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC), a γ-tocopherol metabolite, increased at 3-12 h. The area under the curve from 0 to 72 h and serum maximal concentration of γ-tocopherol were lower than those of α-tocopherol. The time to maximal concentration of γ-tocopherol was faster than that of α-tocopherol. The ratio of urinary excretion of carboxyethyl-hydroxychroman to tocopherol intake was 2.9% for α-CEHC and 7.7% for γ-CEHC. These results revealed that γ-tocopherol is metabolized faster than α-tocopherol in healthy young women.

Topics: Adult; alpha-Tocopherol; Chromans; Chromatography, High Pressure Liquid; Diet; Eating; Female; gamma-Tocopherol; Humans; Japan; Nutritional Status; Propionates; Young Adult

Pregnane X receptor (PXR) is an important nuclear receptor xenosensor that regulates the expression of metabolic enzymes and transporters involved in the metabolism of xenobiotics and endobiotics. In this study, ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS), revealed altered urinary metabolomes in both Pxr-null and wild-type mice treated with the mouse PXR activator pregnenolone 16alpha-carbonitrile (PCN). Multivariate data analysis revealed that PCN significantly attenuated the urinary vitamin E metabolite alpha-carboxyethyl hydroxychroman (CEHC) glucuronide together with a novel metabolite in wild-type but not Pxr-null mice. Deconjugation experiments with beta-glucuronidase and beta-glucosidase suggested that the novel urinary metabolite was gamma-CEHC beta-D-glucoside (Glc). The identity of gamma-CEHC Glc was confirmed by chemical synthesis and by comparing tandem mass fragmentation of the urinary metabolite with the authentic standard. The lower urinary CEHC was likely due to PXR-mediated repression of hepatic sterol carrier protein 2 involved in peroxisomal beta-oxidation of branched-chain fatty acids (BCFA). Using a combination of metabolomic analysis and a genetically modified mouse model, this study revealed that activation of PXR results in attenuated levels of the two vitamin E conjugates, and identification of a novel vitamin E metabolite, gamma-CEHC Glc. Activation of PXR results in attenuated levels of the two vitamin E conjugates that may be useful as biomarkers of PXR activation.

Topics: Animals; Chromans; Gene Expression; Humans; Liver; Male; Mass Spectrometry; Metabolomics; Mice; Mice, Knockout; Molecular Structure; Oxidation-Reduction; Pregnane X Receptor; Pregnenolone Carbonitrile; Propionates; Receptors, Steroid; Urine; Vitamin E; Vitamins