title: 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.
abstract: NQO1 [NAD(P)H quinone oxidoreductase 1; also known as DT-diaphorase] is a cytosolic enzyme that catalyses the two-electron reduction of various quinones including vitamin K. The enzyme may play a role in vitamin K metabolism by reducing vitamin K to vitamin K hydroquinone for utilization in the post-translational γ-glutamyl carboxylation reactions required by several proteins involved in blood coagulation. The aim of the present study was to assess the contribution of NQO1 to vitamin K reduction and haemostasis in an in vivo model. We examined the contribution of NQO1 to haemostasis by examining survival rates in mice poisoned with the anticoagulant warfarin. Supraphysiological amounts of vitamin K sufficiently reversed the effects of warfarin in both wild-type and NQO1-deficient mice. Additionally, vitamin K reductase activities distinct from VKOR (vitamin K epoxide reductase) and NQO1 were measured in vitro from both wild-type and NQO1-defecient mice. The results of the present study suggest that NQO1 does not play a major role in the production of vitamin K hydroquinone and supports the existence of multiple vitamin K reduction pathways. The properties of a NAD(P)H-dependent vitamin K reductase different from NQO1 are described.
authors.affiliation: *Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, U.S.A.
authors.forename: Brian O
authors.initials: BO
authors.lastname: Ingram
authors.forename: Jared L
authors.initials: JL
authors.lastname: Turbyfill
authors.forename: Peggy J
authors.initials: PJ
authors.lastname: Bledsoe
authors.forename: Anil K
authors.initials: AK
authors.lastname: Jaiswal
authors.forename: Darrel W
authors.initials: DW
authors.lastname: Stafford
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000506:poisoning; D019735:Carbon-Carbon Ligases / Q000378:metabolism; D006487:Hemostasis; D007700:Kinetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008862:Microsomes, Liver / Q000201:enzymology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D024482:Vitamin K 2 / Q000378:metabolism*; D014859:Warfarin / Q000506:poisoning
chemical_list: D000925:Anticoagulants; D024482:Vitamin K 2; D014859:Warfarin; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase