Titleω-Hydroxylation of phylloquinone by CYP4F2 is not increased by α-tocopherol.
Publication TypeJournal Article
Year of Publication2013
AuthorsFarley, SM, Leonard, SW, Taylor, AW, Birringer, M, Edson, KZ, Rettie, AE, Traber, M
JournalMolecular nutrition & food research
Volume57
Issue10
Pagination1785-93
Date Published2013 Oct
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.

DOI10.1002/mnfr.201200797