A novel 5 '-carboxychroman metabolite of gamma-tocopherol secreted by HepG2 cells and excreted in human urine

HepG2 cells were incubated with A medium containing fetal bovine serum enri ched with RRR-gamma-tocopherol (gamma-TOH). After 48 h the medium was extra cted and analyzed for gamma-TOH metabolites by gas chromatography-mass spec trometry, In addition to gamma-CEHC, the 3'-carboxychroman metabolite of ga mma-TOH previously reported in human urine, these cells secreted a second s ubstance whose extraction and mass spectral characteristics were consistent with those of the 5'-carboxychroman analog of gamma-CEHC, 2,7,8-trimethyl- 2-(delta-carboxymethylbutyl)-6-hydroxychroman, This is the first report of metabolism of gamma-TOH to carboxychroman metabolites in cell culture. Anal ysis of human urine samples revealed the consistent presence of the novel 5 '-carboxychroman metabolite, along with that of gamma-CEHC, Oral supplement ation with purified RRR-gamma-TOH resulted in elevated urinary concentratio ns of both metabolites, although the concentration of the 5'-gamma-carboxyc hroman metabolite was consistently and substantially less than that of gamm a-CEHC. The presence of both metabolites is consistent with the involvement of an omega-oxidation-like process in the phytyl tail shortening of gamma- TOH to water soluble metabolites excreted in urine. (C) 2000 Academic Press .