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Mol Nutr Food Res. 2013 Oct;57(10):1785-93. doi: 10.1002/mnfr.201200797. Epub 2013 May 3.

ω-Hydroxylation of phylloquinone by CYP4F2 is not increased by α-tocopherol.

Author information

1
Linus Pauling Institute, Oregon State University, Corvallis, OR, USA; Nutrition Graduate Program, School of Biological and Population Health Sciences Oregon State University, Corvallis, OR, USA.

Abstract

SCOPE:

The objective of this study was to investigate the initial catabolic step of vitamin E and K metabolism, the ω-hydroxylation by human cytochrome P450 4F2 (CYP4F2).

METHODS AND RESULTS:

Tocopherol (T) metabolism was compared using rat liver slices incubated with deuterated (d₆)-RRR-α-T (d₆-α-T), racemic 2S-α-T (2S, 4'RS, 8'RS α-T, 2S-α-T), or d₂-γ-T (d₂-γ-T). Following comparable uptake of each T by liver slices, twice as much 13'-OH-T was produced from 2S-α-T or d₂-γ-T (39 ± 15 or 42 ± 5 pmol/g liver, respectively) as from d₆-α-T (17 ± 2, p < 0.01). Kinetic studies were conducted using insect microsomes expressing human CYP4F2 incubated with d₄-phylloquinone (d₄-PK), d₆-RRR-α-T, d₃-SRR-α-T, or d₂-γ-T. CYP4F2 demonstrated similar apparent maximal velocities (Vmax) when either of the α-Ts were used as substrates, which were less than the apparent d₄-PK Vmax (p < 0.0002), while the CYP4F2 catalytic efficiency toward d₄-PK (15.8 Vmax/Km) was five times greater than for α-Ts. Vitamin K had no effect on vitamin E catabolism, while vitamin E slightly decreased the d₄-PK Vmax.

CONCLUSION:

CYP4F2 discriminates between Ts and PK in vitro, but α-T does not apparently increase PK ω-hydroxylation by this mechanism.

KEYWORDS:

5C- and 7C-aglycones; CEHC; CYP4F2; Phylloquinone; Tocopherol

PMID:
23650179
PMCID:
PMC3833818
DOI:
10.1002/mnfr.201200797
[Indexed for MEDLINE]
Free PMC Article
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