scholarly journals Warfarin poisoning and vitamin K antagonism in rat and human liver. Design of a system in vitro that mimics the situation in vivo

1987 ◽  
Vol 241 (2) ◽  
pp. 389-396 ◽  
Author(s):  
R Wallin ◽  
L F Martin
Keyword(s):  
Vitamin K ◽  
Human Liver ◽  
Vitamin K1 ◽  
Active Vitamin ◽  
Vitamin K Epoxide Reductase ◽  
Human System ◽  
Epoxide Reductase ◽  
K Function

The present paper describes a system in vitro that has been developed to mimic vitamin K metabolism and vitamin K function in liver. In this system the two pathways that are known to participate in vitamin K reduction are active and the vitamin K-dependent carboxylase accepts a synthetic pentapeptide as substrate. With this system in vitro the effect of warfarin on both pathways was examined under conditions which simulated a warfarin-poisoned liver. Identical experiments were completed with rat and human liver. All activities currently associated with vitamin K metabolism and vitamin K function were similar in the rat and human systems. Warfarin neutralized the ability of pathway I (the vitamin K epoxide reductase pathway) to produce reduced and active vitamin K cofactor for the carboxylase. In both the rat and the human system, however, when warfarin was present, reduced vitamin K cofactor was produced by pathway II (the dehydrogenase pathway). The data are consistent with observations in vivo on the effect of vitamin K1 when used as an antidote. This suggests that the system in vitro reflects the mechanism in vivo by which vitamin K1 overcomes warfarin poisoning.

Comparison of vitamin K1 and K2 kinetics of vitamin K epoxide reductase C1

2008 ◽  
Vol 28 (S 01) ◽  
pp. S106-S106
Author(s):  
P. Westhofen ◽  
M. Watzka ◽  
M. Hass ◽  
C. Müller-Reible ◽  
D. Lütjohann ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K1 ◽  
Vitamin K Epoxide Reductase ◽  
Epoxide Reductase ◽  
Kinetics Of

Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by γ-carboxylation-dependent and -independent mechanisms

2009 ◽  
Vol 297 (6) ◽  
pp. C1358-C1367 ◽  
Author(s):  
Gerald J. Atkins ◽  
Katie J. Welldon ◽  
Asiri R. Wijenayaka ◽  
Lynda F. Bonewald ◽  
David M. Findlay
Keyword(s):  
Bone Formation ◽  
Vitamin K ◽  
Type I Collagen ◽  
Vitamin K2 ◽  
Type I ◽  
Vitamin K1 ◽  
Vitamin K3 ◽  
Positive Effect

The vitamin K family members phylloquinone (vitamin K1) and the menaquinones (vitamin K2) are under study for their roles in bone metabolism and as potential therapeutic agents for skeletal diseases. We have investigated the effects of two naturally occurring homologs, phytonadione (vitamin K1) and menatetrenone (vitamin K2), and those of the synthetic vitamin K, menadione (vitamin K3), on human primary osteoblasts. All homologs promoted in vitro mineralization by these cells. Vitamin K1-induced mineralization was highly sensitive to warfarin, whereas that induced by vitamins K2 and K3 was less sensitive, implying that γ-carboxylation and other mechanisms, possibly genomic actions through activation of the steroid xenobiotic receptor, are involved in the effect. The positive effect on mineralization was associated with decreased matrix synthesis, evidenced by a decrease from control in expression of type I collagen mRNA, implying a maturational effect. Incubation in the presence of vitamin K2 or K3 in a three-dimensional type I collagen gel culture system resulted in increased numbers of cells with elongated cytoplasmic processes resembling osteocytes. This effect was not warfarin sensitive. Addition of calcein to vitamin K-treated cells revealed vitamin K-dependent deposition of mineral associated with cell processes. These effects are consistent with vitamin K promoting the osteoblast-to-osteocyte transition in humans. To test whether vitamin K may also act on mature osteocytes, we tested the effects of vitamin K on MLO-Y4 cells. Vitamin K reduced receptor activator of NF-κB ligand expression relative to osteoprotegerin by MLO-Y4 cells, an effect also seen in human cultures. Together, our findings suggest that vitamin K promotes the osteoblast-to-osteocyte transition, at the same time decreasing the osteoclastogenic potential of these cells. These may be mechanisms by which vitamin K optimizes bone formation and integrity in vivo and may help explain the net positive effect of vitamin K on bone formation.

Vitamin K Antagonism of Coumarin Intoxication in the Rat

1986 ◽  
Vol 55 (02) ◽  
pp. 235-239 ◽  
Author(s):  
R Wallin ◽  
D Susan ◽  
D Patrick ◽  
J O Ballard
Keyword(s):  
Vitamin K ◽  
Liver Microsomes ◽  
Clotting Factor ◽  
Vitamin K1 ◽  
Clotting Factors ◽  
Strong Inhibitor ◽  
In Vitro System ◽  
High Concentrations

SummaryAn in vitro system which expresses all enzyme activities related to vitamin K-dependent carboxylation of blood clotting factors was prepared from livers of rats overdosed with warfarin, difenacoum and dicumarol respectively. In this system, the activities of the two pathways that are known to produce active reduced vitamin K1 cofactor for the carboxylation reaction were measured. Also the ability of high concentrations of vitamin Kx to overcome inhibition of clotting factor synthesis was studied. In the systems prepared from livers of warfarin and difenacoum intoxicated rats, pathway I was inactive. Vitamin K epoxide reductase was also inactive which strongly suggests that this enzyme catalyzes the activity of pathway I in vivo. Reduction of vitamin by pathway II bypassed the inactive pathway I and resulted in carboxylation activity. This pathway therefore mediates the antidotic effect of vitamin K1 in the coumarin intoxicated liver. In the in vitro system prepared from dicumarol intoxicated livers the activity of pathway I was not significantly affected. Dicumarol however was a strong inhibitor when added to liver microsomes in vitro.

scholarly journals Comparison of two reducing agents dithiothreitol and tris(3-hydroxypropyl)phosphine for in vitro kinetic assay of vitamin K epoxide reductase

2020 ◽  
Vol 9 ◽  
pp. 100095 ◽  
Author(s):  
Kazuki Takeda ◽  
Ayuko Morita ◽  
Yoshinori Ikenaka ◽  
Shouta M.M. Nakayama ◽  
Mayumi Ishizuka
Keyword(s):  
Vitamin K ◽  
Reducing Agents ◽  
Kinetic Assay ◽  
Vitamin K Epoxide Reductase ◽  
Epoxide Reductase
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