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Novel metabolic and non‐metabolic mechanisms influencing bioavailability of vitamin E
Author(s) -
Bardowell Sabrina,
Ding XinXing,
Parker Robert
Publication year - 2013
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.27.1_supplement.358.3
Subject(s) - bioavailability , vitamin , metabolism , microsome , chemistry , catabolism , kidney , vitamin e , medicine , endocrinology , reductase , antioxidant , enzyme , biochemistry , biology , pharmacology
Bioavailability of the antioxidant vitamin E is vitamer‐dependent, and in part involves hepatic catabolism via side‐chain oxidation and urinary excretion. Here we report new insights into both enzymatic and non‐enzymatic elimination pathways, using mice with either global disruption in Cyp4f14 (a murine vitamin E hydroxylase) or liver‐specific disruption in cytochrome P450 reductase (L‐CPR). The substantial deficit in vitamin E metabolism observed in both models was counterbalanced by increased fecal elimination of unchanged tocopherols in supplemented mice, revealing a major mechanism limiting tissue vitamin E accumulation. This mechanism may account for the observed reduction in bioavailability of all forms of vitamin E at elevated intakes in humans. L‐CPR mice, devoid of all vitamin E oxidase activity in the liver, still excreted substantial amounts of ω‐oxidation metabolites in urine and feces. Analysis of microsomes from other mouse tissues revealed vitamin E hydroxylase activity in adipose tissue, brain, and kidney, but not lung. Appreciable activity was observed in the small intestine, the portal of entry. Microsomes from human liver, intestine and kidney, but not lung, all exhibited activity, illustrating both central (liver) and organ‐specific control over the types and amounts of tocopherols that accumulate in tissues. Funded by NIH DK‐007158 and DK‐067494.