Mechanism Of Action Of Vitamin K: Synthesis Of Y-Carboxyglutamic Aci

Suttie, J. W.; Nelsestuen, Gary L.

doi:10.3109/10409238009105469

Cited by 219 publications

(109 citation statements)

References 164 publications

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“…The pharmacological target of these rodenticides is vitamin K 2,3-epoxide reductase (VKOR), which catalyzes the reduction of vitamin K 2,3-epoxide (VKO) and vitamin K (Figure 1). Because reduced vitamin K is required for the post-translational formation of γ-carboxyglutamyl residues from Glu residues in clotting factors II, VII, IX, and X (Suttie and Nelsestuen , 1980), the inhibition of VKOR by coumarin derivatives causes lethal hemorrhages in rodents (Thijssen et al, 2004;Cain et al, 1998). Meanwhile, coumarin derivative anticoagulants are metabolized by cytochrome P450 (CYP), which consists of a large number of isoforms.…”

Section: Introductionmentioning

confidence: 99%

Comparison of warfarin sensitivity between rat and bird species

Watanabe

Saengtienchai

Tanaka

et al. 2010

Comparative Biochemistry and Physiology Part C: Toxicology &

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Scattering coumarin-derivative rodenticides in broad areas have caused primary-and secondary-poisoning incidents in non-target wild birds. In this study, we compared factors determining warfarin sensitivity between bird species and rats based on vitamin K 2,3-epoxide reductase (VKOR) kinetics, VKOR inhibition by warfarin and warfarin metabolism assays. In VKOR characterization, chickens and ostriches showed significantly lower enzymatic efficiencies than rats (one-sixth and one-third, respectively), suggesting bird species depend more on a non-VKOR vitamin K source. On the other hand, the inhibition constants (K i ) of VKOR for warfarin were significantly different between chickens and ostriches (11.3 ± 2.5 μM and 0.64 ± 0.39 μM, respectively). Interestingly, the ostrich K i was similar to the values for rats (0.28 ± 0.09 μM). The K i results reveal a surprising possibility that VKOR in some bird species are easily inhibited by warfarin. Warfarin metabolism assays also showed a large inter-species difference in bird species. Chickens and ostriches showed higher metabolic activity than that of rats, while mallards and owls showed only a slight ability to metabolize warfarin. In this study, we clarified the wide inter-species difference that exists among birds in xenobiotic metabolism and sensitivity to a rodenticide.

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Section: Introductionmentioning

confidence: 99%

Comparison of warfarin sensitivity between rat and bird species

Watanabe

Saengtienchai

Tanaka

et al. 2010

Comparative Biochemistry and Physiology Part C: Toxicology &

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“…The four vitamin K-dependent clotting factors are synthesized in the liver, and during their synthesis they undergo a number of post-translational modifications, one of which is the vitamin K-dependent carboxylation of a number of glutamic acid residues [1,2]. The in vivo carboxylation reaction is inhibited by the oral administration of vitamin K-antagonists such as warfarin or dicoumarol.…”

Section: Introductionmentioning

confidence: 99%

Characteristics of vitamin K‐dependent carboxylating systems from human liver and placenta

1982

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Bovine liver vitamin K‐dependent carboxylase was compared with that obtained from human liver and placenta. Human liver microsomal preparations contained more endogenous substrate than did bovine preparations, but no differences were found between the two types of hepatic enzyme. This observation demonstrates that the bovine liver carboxylating enzyme system is a good model system which will help us to understand vitamin K action in man. Placental carboxylase differed from the liver systems because only vitamin K hydroquinone and not vitamin K quinone could be used as a coenzyme for the carboxylation reaction. Obviously, vitamin K reductase was absent in these preparations.

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“…13 Currently, approximately 14 vitamin K-dependent proteins are known, with broad spectrum efficacy on haemostasis, calcium metabolism, control of cell growth, apoptosis and signal transduction ( Table 1). [14][15][16][17] Following elucidation of the vitamin's haemostasiological significance and research into further vitamin K-dependent Gla proteins, such as osteocalcin (BGP D bone Gla protein) and matrix Gla protein (MGP), current research is focusing on the vitamin's effect on bone and vascular health. 10,13,18 The K Vitamers: Nomenclature, Structure and Occurrence…”

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confidence: 99%