title: ω-Hydroxylation of phylloquinone by CYP4F2 is not increased by α-tocopherol.
abstract: METHODS
  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).
  
  
  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.
  
  
  CONCLUSIONS
  CYP4F2 discriminates between Ts and PK in vitro, but α-T does not apparently increase PK ω-hydroxylation by this mechanism.
authors: 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.
authors: Sherry M
authors: SM
authors: Farley
authors: Scott W
authors: SW
authors: Leonard
authors: Alan W
authors: AW
authors: Taylor
authors: Marc
authors: M
authors: Birringer
authors: Katheryne Z
authors: KZ
authors: Edson
authors: Allan E
authors: AE
authors: Rettie
authors: Maret G
authors: MG
authors: Traber
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D000072470:Cytochrome P450 Family 4; D019587:Dietary Supplements; D006801:Humans; D006900:Hydroxylation / Q000187:drug effects; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D010837:Vitamin K 1 / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D010837:Vitamin K 1; D000255:Adenosine Triphosphate; D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; D024502:alpha-Tocopherol
keywords: 5C- and 7C-aglycones; CEHC; CYP4F2; Phylloquinone; Tocopherol
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