Abstract
The widely conserved preferential accumulation of α-tocopherol (α-TOH) in tissues occurs, in part, from selective postabsorptive catabolism of non-α-TOH forms via the vitamin E-ω-oxidation pathway. We previously showed that global disruption of CYP4F14, the major but not the only mouse TOH-ω-hydroxylase, resulted in hyper-accumulation of γ-TOH in mice fed a soybean oil diet. In the current study, supplementation of Cyp4f14-/- mice with high levels of δ- and γ-TOH exacerbated tissue enrichment of these forms of vitamin E. However, at high dietary levels of TOH, mechanisms other than ω-hydroxylation dominate in resisting diet-induced accumulation of non-α-TOH. These include TOH metabolism via ω-1/ω-2 oxidation and fecal elimination of unmetabolized TOH. The ω-1 and ω-2 fecal metabolites of γ- and α-TOH were observed in human fecal material. Mice lacking all liver microsomal CYP activity due to disruption of cytochrome P450 reductase revealed the presence of extra-hepatic ω-, ω-1, and ω-2 TOH hydroxylase activities. TOH-ω-hydroxylase activity was exhibited by microsomes from mouse and human small intestine; murine activity was entirely due to CYP4F14. These findings shed new light on the role of TOH-ω-hydroxylase activity and other mechanisms in resisting diet-induced accumulation of tissue TOH and further characterize vitamin E metabolism in mice and humans.
Original language | English (US) |
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Pages (from-to) | 2667-2676 |
Number of pages | 10 |
Journal | Journal of Lipid Research |
Volume | 53 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2012 |
Keywords
- CYP4F14
- CYP4F2
- Cytochrome P450 reductase
- Diet
- Fecal elimination
- Intestine
- Knockout mouse
- Liver
- Metabolites
- ω-oxidation
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Cell Biology