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.
SCOPE: The objective of this study was to investigate the initial catabolic step of vitamin E and K metabolism, the ω-hydroxylation by humancytochrome 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 humanCYP4F2 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.
Authors: Sherry M Farley; Scott W Leonard; Edwin M Labut; Hannah F Raines; David J Card; Dominic J Harrington; Debbie J Mustacich; Maret G Traber Journal: Mol Nutr Food Res Date: 2012-06 Impact factor: 5.914
Authors: Debbie J Mustacich; Scott W Leonard; Michael W Devereaux; Ronald J Sokol; Maret G Traber Journal: Free Radic Biol Med Date: 2006-07-04 Impact factor: 7.376
Authors: Alison Tovar; Clement K Ameho; Jeffrey B Blumberg; James W Peterson; Donald Smith; Sarah L Booth Journal: Nutr Metab (Lond) Date: 2006-07-20 Impact factor: 4.169