Disruption of P450-mediated vitamin E hydroxylase activities alters vitamin E status in tocopherol supplemented mice and reveals extra-hepatic vitamin E metabolism

Sabrina A. Bardowell, Xinxin Ding, Robert S. Parker

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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 languageEnglish (US)
Pages (from-to)2667-2676
Number of pages10
JournalJournal of Lipid Research
Volume53
Issue number12
DOIs
StatePublished - 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

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