Vitamin K1 2,3-epoxide and quinone reduction: mechanism and inhibition.

@article{Preusch1990VitaminK2,
  title={Vitamin K1 2,3-epoxide and quinone reduction: mechanism and inhibition.},
  author={Peter C. Preusch and David M. Smalley},
  journal={Free radical research communications},
  year={1990},
  volume={8 4-6},
  pages={
          401-15
        }
}
The chemical and enzymatic pathways of vitamin K1 epoxide and quinone reduction have been investigated. The reduction of the epoxide by thiols is known to involve a thiol-adduct and a hydroxy vitamin K enolate intermediate which eliminates water to yield the quinone. Sodium borohydride treatment resulted in carbonyl reduction generating relatively stable compounds that did not proceed to quinone in the presence of base. NAD(P)H:quinone oxidoreductase (DT-diaphorase, E.C. 1.6.99.2) reduction of… Expand
Assessment of the contribution of NAD(P)H-dependent quinone oxidoreductase 1 (NQO1) to the reduction of vitamin K in wild-type and NQO1-deficient mice.
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  • Chemistry, Medicine
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  • 2004
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The results indicate that warfarin uncouples the 2 reactions that fully reduce KO, and this activity appears to cooperate with VKORC1 to accomplish full KO reduction. Expand
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References

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TLDR
Data establish that exogenous thiol compounds promote the reduction of at least one protein disulfide which participates in the metabolism of vitamin K and vitamin K 2,3-epoxide. Expand
Lapachol inhibition of vitamin K epoxide reductase and vitamin K quinone reductase.
TLDR
It is proposed that lapachol assumes a 4-enol tautomeric structure similar to that of the 4-hydroxy coumarins, analogs of the postulated hydroxyvitamin K enolate intermediate bound to the oxidized form of the enzyme in the chemical reaction mechanism of vitamin K epoxide reductase, thus explaining their high affinity. Expand
DT-diaphorase as a quinone reductase: a cellular control device against semiquinone and superoxide radical formation.
TLDR
The results support the earlier proposal that DT-diaphorase serves as a cellular control device against quinone toxicity and reflects the relative contributions of the two pathways. Expand
Studies of the vitamin K-dependent carboxylase and vitamin K epoxide reductase in rat liver.
TLDR
The primary vitamin K-dependent event has now been shown to be the abstraction of the gamma-hydrogen of the substrate Glu residue with the concurrent formation of vitamin K 2,3-epoxide. Expand
Sulfaquinoxaline inhibition of vitamin K epoxide and quinone reductase.
TLDR
Results suggest that this inhibitor binds to the oxidized form of vitamin K epoxide reductase in the same way as suggested for the coumarins and hydroxyquinones. Expand
DT-diaphorase-catalyzed two-electron reduction of quinone epoxides.
DT-diaphorase catalyzes the two-electron reduction of the unsubstituted quinone epoxide, 2,3-epoxy-p-benzoquinone, at expense of NAD(P)H with formation of 2-OH-p-benzohydroquinone as the reactionExpand
Vitamin K epoxide reductase: evidence that vitamin K dihydroquinone is a product of vitamin K epoxide reduction.
  • P. Sherman, E. Sander
  • Chemistry, Medicine
  • Biochemical and biophysical research communications
  • 1981
TLDR
Carboxymethyl cellulose chromatography suggests that the same cytosolic protein fraction may be involved in the dithiothreitol-supported reduction of Vitamin K epoxide, the dITHioth reitol- supported reduction of vitamin K quinone and the NADH-supported Reduction of dichlorophenol-indophenol. Expand
Reduced thioredoxin: a possible physiological cofactor for vitamin K epoxide reductase. Further support for an active site disulfide.
TLDR
Vitamin K 2,3-epoxide reductase activity from liver microsomes requires only a thiol cofactor, particularly dithiothreitol (DTT), and thioredoxin is significantly more active than either DTT or reduced lipoic acid in both systems. Expand
Relationship of dithiothreitol-dependent microsomal vitamin K quinone and vitamin K epoxide reductases inhibition of epoxide reduction by vitamin K quinone.
TLDR
Vitamin K quinone was shown to be an effective inhibitor of vitamin K epoxide reduction by whole rat liver microsomes, suggesting segregation of the compounds into different microsomal vesicles under certain conditions. Expand
Indirect inhibition of vitamin K epoxide reduction by salicylate
TLDR
The concentrations of salicylate at which significant inhibitory effects are exerted in‐vitro (50–100 μm) are below the 200 μm levels observed in the livers of rats given an anticoagulating dose of salingylate. Expand
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