|Title||ω-Hydroxylation of phylloquinone by CYP4F2 is not increased by α-tocopherol.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Farley SM, Leonard SW, Taylor AW, Birringer M, Edson KZ, Rettie AE, Traber MG|
|Journal||Mol Nutr Food Res|
|Date Published||2013 Oct|
|Keywords||Adenosine Triphosphate, alpha-Tocopherol, Animals, Chromatography, High Pressure Liquid, Cytochrome P-450 Enzyme System, Cytochrome P450 Family 4, Dietary Supplements, Humans, Hydroxylation, In Vitro Techniques, Liver, Male, Microsomes, Liver, Rats, Rats, Sprague-Dawley, Tandem Mass Spectrometry, Vitamin K 1|
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.
|Alternate Journal||Mol Nutr Food Res|
|PubMed Central ID||PMC3833818|
|Grant List||GM06797 / GM / NIGMS NIH HHS / United States |
R01 DK067930 / DK / NIDDK NIH HHS / United States
R01 GM068797 / GM / NIGMS NIH HHS / United States
DK067930 / DK / NIDDK NIH HHS / United States
R01 GM109743 / GM / NIGMS NIH HHS / United States