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Investigation of ω‐hydroxylation of tocopherols by CYP4F2 and by rat liver slices
Author(s) -
Farley Sherry M.,
Leonard Scott W.,
Mustacich Debbie J.,
Labut Edwin M.,
Traber Maret G.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.534.2
Subject(s) - hydroxylation , chemistry , tocopherol , microsome , metabolism , stereochemistry , medicine , endocrinology , biochemistry , antioxidant , in vitro , vitamin e , biology , enzyme
The ω‐hydroxylation of 2 S ‐α‐tocopherol (2 S , 4′ RS , 8′ RS α‐tocopherol) and deuterated (d 2 )‐ γ‐tocopherol (d 2 ‐γ‐T), relative to d 6 ‐ RRR ‐α‐tocopherol (d 6 ‐α‐T) was studied. Rat liver slices were incubated with d 6 ‐α‐T, d 2 ‐γ‐T, or 2 S ‐α‐T and their metabolism to 13′‐OH was measured by LC‐MS/MS. Although uptake of each form by liver slices was comparable, 2 S ‐α‐T and d 2 ‐γ‐T were more readily metabolized to 13′‐OH (39 ± 15 pmol/g and 42 ± 5, respectively, p<0.01), than was d 6 ‐α‐T (17 ±2). When these tocopherols were incubated with microsomes expressing human recombinant CYP4F2, there was greater production (p<0.001) of d 2 ‐γ‐T‐13′‐OH (0.36 ± 0.05 pmol 13′‐OH/pmol CYP4F2) compared to d 6 ‐α‐T‐13′‐OH (0.08 ± 0.02); however, there was no preference for 2 S ‐α‐T over d 6 ‐α‐T. These data indicate that CYP4F2‐mediated ω‐hydroxylation does not differentiate between side chain stereoisomers and that structural differences in the chroman ring are more influential. This study also suggests that other factors present in liver slices, such as selectivity of α‐T transfer protein, are responsible in regulating metabolism of natural versus synthetic α‐T. Grant Funding Source : NIH, ODS, Archer Daniels Midland, and USDA