Dataset Information

?-Hydroxylation of phylloquinone by CYP4F2 is not increased by ?-tocopherol.

ABSTRACT: SCOPE:The objective of this study was to investigate the initial catabolic step of vitamin E and K metabolism, the ?-hydroxylation by human cytochrome P450 4F2 (CYP4F2). METHODS AND RESULTS:Tocopherol (T) metabolism was compared using rat liver slices incubated with deuterated (d?)-RRR-?-T (d?-?-T), racemic 2S-?-T (2S, 4'RS, 8'RS ?-T, 2S-?-T), or d?-?-T (d?-?-T). Following comparable uptake of each T by liver slices, twice as much 13'-OH-T was produced from 2S-?-T or d?-?-T (39 ± 15 or 42 ± 5 pmol/g liver, respectively) as from d?-?-T (17 ± 2, p < 0.01). Kinetic studies were conducted using insect microsomes expressing human CYP4F2 incubated with d?-phylloquinone (d?-PK), d?-RRR-?-T, d?-SRR-?-T, or d?-?-T. CYP4F2 demonstrated similar apparent maximal velocities (Vmax) when either of the ?-Ts were used as substrates, which were less than the apparent d?-PK Vmax (p < 0.0002), while the CYP4F2 catalytic efficiency toward d?-PK (15.8 Vmax/Km) was five times greater than for ?-Ts. Vitamin K had no effect on vitamin E catabolism, while vitamin E slightly decreased the d?-PK Vmax. CONCLUSION:CYP4F2 discriminates between Ts and PK in vitro, but ?-T does not apparently increase PK ?-hydroxylation by this mechanism.

SUBMITTER: Farley SM

PROVIDER: S-EPMC3833818 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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

Farley Sherry M SM Leonard Scott W SW Taylor Alan W AW Birringer Marc M Edson Katheryne Z KZ Rettie Allan E AE Traber Maret G MG

Molecular nutrition & food research 20130503 10

<h4>Scope</h4>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).<h4>Methods and results</h4>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 ± ...[more]

PMID: 23650179

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Project description:BackgroundVitamin E (vitE) is hypothesized to attenuate age-related decline in pulmonary function.ObjectivesWe investigated the association between change in plasma vitE (∆vitE) and pulmonary function decline [forced expiratory volume in the first second (FEV1)] and examined genetic and nongenetic factors associated with ∆vitE.MethodsWe studied 1144 men randomly assigned to vitE in SELECT (Selenium and Vitamin E Cancer Prevention Trial). ∆vitE was the difference between baseline and year 3 vitE concentrations measured with GC-MS. FEV1 was measured longitudinally by spirometry. We genotyped 555 men (vitE-only arm) using the Illumina Expanded Multi-Ethnic Genotyping Array (MEGAex). We used mixed-effects linear regression modeling to examine the ∆vitE-FEV1 association.ResultsHigher ∆vitE was associated with lower baseline α-tocopherol (α-TOH), higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (as opposed to African) (all P < 0.05), and the minor allele of a missense variant in cytochrome P450 family 4 subfamily F member 2 (CYP4F2) (rs2108622-T; 2.4 µmol/L higher ∆vitE, SE: 0.8 µmol/L; P = 0.0032). Higher ∆vitE was associated with attenuated FEV1 decline, with stronger effects in adherent participants (≥80% of supplements consumed): a statistically significant ∆vitE × time interaction (P = 0.014) indicated that a 1-unit increase in ∆vitE was associated with a 2.2-mL/y attenuation in FEV1 decline (SE: 0.9 mL/y). The effect size for 1 SD higher ∆vitE (+4 µmol/mmol free-cholesterol-adjusted α-TOH) was roughly one-quarter of the effect of 1 y of aging, but in the opposite direction. The ∆vitE-FEV1 association was similar in never smokers (2.4-mL/y attenuated FEV1 decline, SE: 1.0 mL/y; P = 0.017, n = 364), and current smokers (2.8-mL/y, SE: 1.6 mL/y; P = 0.079, n = 214), but there was little to no effect in former smokers (-0.64-mL/y, SE: 0.9 mL/y; P = 0.45, n = 564).ConclusionsGreater response to vitE supplementation was associated with attenuated FEV1 decline. The response to supplementation differed by rs2108622 such that individuals with the C allele, compared with the T allele, may need a higher dietary intake to reach the same plasma vitE concentration.

Dataset Information

?-Hydroxylation of phylloquinone by CYP4F2 is not increased by ?-tocopherol.

Publications

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

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