AnatomyDiseasesChemicals and DrugsPhenomena and ProcessesDisciplines and OccupationsTechnology, Industry, Agriculture
Vitamin K Epoxide ReductasesVitamin K 1Vitamin KMixed Function OxygenasesWarfarinCarbon-Carbon LigasesAcenocoumarolVitamin K DeficiencyAryl Hydrocarbon HydroxylasesAnticoagulantsPharmacogeneticsVitamin K 2Epoxide HydrolasesDithiothreitolGenotypePolymorphism, Single NucleotideVitamin K Deficiency BleedingEpoxy Compounds4-HydroxycoumarinsBlood Coagulation Disorders, InheritedVitamin AVitamin K 3Microsomes, LiverVitaminsDrug Resistance
VKORC1EnzymeVKORPolymorphismInhibitsQuinoneComplexAntagonistRecyclesCarboxylationSynthesisProteinPreventsLiverBacterialInhibitionDosesProduction of coagulation proteinsCarboxylaseDeficientCoagulation cascadeDeficiencyProthrombinAnticoagulationActive vitaminDoseIntakeSupplementationFormCardiovascularHumanDependentFunctionalBloodLevels
VKORC114
  • Genetic variants of the enzyme that metabolizes warfarin, cytochrome P-450 2C9 (CYP2C9), and of a key pharmacologic target of warfarin, vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to various warfarin doses, but the role of these variants during initial anticoagulation is not clear. (nih.gov)
  • The reduction of vitamin K to vitamin K hydrochinon depends on the vitamin K epoxide reductase complex subunit 1 (VKORC1). (qscience.com)
  • The VKORC1 gene provides instructions for making a vitamin K epoxide reductase enzyme. (medlineplus.gov)
  • Warfarin affects the vitamin K-dependent clotting factors II, VII, IX, and X. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of the vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K1 epoxide. (cms.gov)
  • It appears that the exact opposite may be the case since those with the GG genotype apparently have a form of VKORC1 that is better able to regenerate vitamin K hydroquinone (required for carboxylation of the clotting factors) from the vitamin K 2,3-epoxide. (clotcare.com)
  • Genetic variants in the warfarin target, the vitamin K epoxide reductase (VKORC1), as well as the warfarin metabolizing enzyme, cytochrome P450 2C9 (CYP2C9), influence the variation in patient response. (medicineworks.com)
  • Although it might be premature to recommend routine genetic testing, the future development and clinical validation of simple but comprehensive algorithms integrating the most informative gene polymorphisms (VKORC1 and CYP2C9) with some demographic information (age, race, body mass index) and clinical variables (comorbidities, drugs interference), and standardized dietary intake of vitamin K may provide a valuable tool in the care of patients on OAT with conventional VKAs. (edu.au)
  • cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) . (ssht.sk)
  • Warfarin decreases blood coagulation by inhibiting the vitamin K epoxide reductase, encoded by the VKORC1 gene. (ancienthaplogroups.com)
  • The VKORC1 enzyme recycles inactive vitamin K1 after it has helped to activate several proteins involved in clotting. (ancienthaplogroups.com)
  • Pharmacodynamic properties are affected due to variations in genes that affect drug targets, for example the VKORC1 gene which codes for active sites of the enzyme, epoxide reductase. (panaceapharmaprojects.com)
  • Warfarin, an inhibitor of epoxide reductase, has a reduced efficacy in individuals with a genetic polymorphism of the VKORC1 gene. (panaceapharmaprojects.com)
  • By inhibiting vitamin K epoxide reductase complicated 1 (VKORC1), S-warfarin prevents regeneration of vitamin K hydroquinone for activation of vitamin K-dependent clotting elements. (rockinhibitor.com)
  • This really is followed by details on polymorphism of vitamin K epoxide reductase in addition to a note that about 55 with the variability in warfarin dose might be explained by a combination of MedChemExpress VRT-831509 VKORC1 and CYP2C9 genotypes, age, height, body weight, interacting drugs, and indication for warfarin therapy. (rockinhibitor.com)
Enzyme5
  • Vitamin K epoxide reductase (VKOR) is an enzyme (EC 1.17.4.4) that reduces vitamin K after it has been oxidised in the carboxylation of glutamic acid residues in blood coagulation enzymes. (wikipedia.org)
  • The enzyme vitamin K-dependent gamma carboxylase catalyzes precursors of prothrombin and coagulation factors VII, IX and X to prothrombin, and coagulation factors VII, IX and X. From there, these precursors and factors leave the liver cell and enter into the blood capillary bed. (pathbank.org)
  • Phenprocoumon is an anticoagulant that inhibits the liver enzyme vitamin K reductase. (smpdb.ca)
  • It works by inhibiting the activity of vitamin K epoxide reductase, an enzyme necessary to activate certain clotting factors. (therxadvocates.com)
  • This enzyme is responsible for activating vitamin K and coagulation factors. (panaceapharmaprojects.com)
VKOR8
  • The membrane topology of vitamin K epoxide reductase (VKOR) is controversial with data supporting both a three transmembrane and a four transmembrane model. (elsevierpure.com)
  • The positioning of the transmembrane domains and the loops between these domains is critical if we are to understand the mechanism of vitamin K oxidation and its recycling by members of the thioredoxin family of proteins and the mechanism of action of warfarin, an inhibitor of VKOR. (elsevierpure.com)
  • Since vitamin K epoxide reductase (VKOR) is responsible for the synthesis of reduced vitamin K, warfarin, by targeting at and inhibiting VKOR, can block the activation of clotting factors and decrease the blood clot [ 3 ]. (hindawi.com)
  • Growing evidence indicates that up to 60% of the individual pharmacological response to coumarins might be due to genetic variables and affected by polymorphisms in the genes encoding two enzymes, namely, vitamin K epoxide reductase (VKOR) and cytochrome P450 CYP2C9. (edu.au)
  • The vitamin K-epoxide reductase complex (VKOR) allows vit-amin K epoxide to be converted back into reduced vitvit-amin K. Its activity is the rate-limiting step of vitamin K-dependent protein gamma-carboxylation. (123dok.net)
  • Warfarin inhibits vitamin K epoxide reductase (VKOR). (comu.edu.tr)
  • Well-known 4-hydroxycoumarin derivatives, such as warfarin, act as inhibitors of the vitamin K epoxide reductase (VKOR) and are used as anticoagulants. (bvsalud.org)
  • Vitamin K 2,3-epoxide acts as a substrate for vitamin K 2,3-epoxide reductase (VKOR) complex. (com.vn)
Polymorphism1
Inhibits2
  • This medication inhibits epoxide reductase. (picmonic.com)
  • Warfarin inhibits the activity of vitamin K epoxide reductase and prevents recycling of vitamin K back to the reduced form, thus interfering with the synthesis of factor VII and other vitamin K-dependent factors. (medscape.com)
Quinone2
  • The VKORL1 complex it forms is much less efficient at reducing the epoxide, but it has the ability to reduce the quinone form of vitamin K to a diol form (KH2). (wikipedia.org)
  • Hydrogen sulfide poisoning: Emergency management of therapeutic doses and intervals for repeated doses of vitamin k reductases (epoxide reductase and quinone reductase), which maintain vitamin k. (revivemedicalny.com)
Complex1
  • It can deplete functional vitamin K reserves and thereby reduce the synthesis of active clotting factors by competitively inhibiting multi-unit vitamin K epoxide reductase complex. (icliniq.com)
Antagonist6
Recycles1
  • Recycles vitamin K epoxide to the reduced form of vitamin K, an essential cofactor in formation of active clotting factors II, VII, IX and X via gamma-glutamyl carboxylation. (standardofcare.com)
Carboxylation3
  • Increasing vitamin K intake has been shown to increase carboxylation of extra-hepatic VKD proteins in apparently healthy adults, as well as those with osteoporosis and atherosclerosis. (vitamindwiki.com)
  • Vitamin K, discovered in the 1930s, functions as a cofactor for the posttranslational carboxylation of glutamate residues (1). (123dok.net)
  • As vitamin K is a cofactor for the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulation factors (II, VII, IX, and X), this ultimately results in reduced cleavage of fibrinogen into fibrin and decreased coagulability of the blood. (smpdb.ca)
Synthesis4
  • Vitamin K is required in the synthesis of 4 clotting factors in the liver: factors II,VII, IX, and X. It is also essential in the production of protein C and S, which are anticoagulant proteins. (medscape.com)
  • In infants, the low transmission of vitamin K (VK) across the placenta, liver prematurity with prothrombin synthesis, lack of VK in breast milk, and the sterile gut in neonates account for VK deficiency. (medscape.com)
  • It works by inhibiting epoxide reductase, leading to interference in the synthesis of vitamin K-dependent clotting factors (II, VII, IX, X, C and S).Side effects of warfarin include bleeding, which necessitates the monitoring of a patient's INR, as well as necrosis, which is more common in protein C-deficient patients. (picmonic.com)
  • Hence, when a problem with synthesis occurs, as in liver failure, vitamin K deficiency, or warfarin therapy, the factor VII level first decreases in the plasma, followed by a decrease in other vitamin K-dependent factors. (medscape.com)
Protein4
  • even in all healthy humans tested, a significant percentage of the extra-hepatic VKD proteins, which are activated by vitamin K2, e.g., osteocalcin and matrix Gla-protein, are only partly carboxylated and therefore inactive. (vitamindwiki.com)
  • Matrix Gla protein and bone Gla protein (osteocalcin), two vitamin K-dependent proteins involved in calcium home-ostasis, have been implicated in the pathogenesis of athero-sclerosis, myocardial infarction and stroke (2, 3). (123dok.net)
  • This medication acts on the extrinsic pathway by preventing the activation of vitamin K, warfarin reduces the production of factors II, VII, IX and X (also Protein C and S). (picmonic.com)
  • Preclinical studies have shown that several vitamin K-dependent proteins, such as matrix Gla protein and osteopontin, play a role in bone metabolism [ 9 ], and this has led to concerns that warfarin may increase the risk for osteoporotic fracture. (biomedcentral.com)
Prevents1
Liver3
  • The anticoagulation effects are currently believed to be due to warfarin interrupting the vitamin K cycle in liver: in coagulation cascade, activated clotting factors are indispensable for the formation of blood clot. (hindawi.com)
  • Vitamin K1 is not commonly deficient: the vitamin K-dependent (VKD) clotting factors, which are carboxylated (activated) by K1 in the liver, have been found to be fully carboxylated in the healthy population. (vitamindwiki.com)
  • Insufficient production of coagulation proteins or limited access to vitamin K by the immature neonatal liver may exacerbate a coagulation defect. (msdvetmanual.com)
Bacterial1
  • Vitamin K2, of bacterial origin, refers to the series of menaquinones that share a common methylated napthoquinone ring structure (thus their mena prefix), but differ in the length and degree of saturation of their aliphatic side chain. (vitamindwiki.com)
Inhibition1
  • This framework describes chemical properties of ARs, established macromolecular interactions by inhibition of vitamin K epoxide reductase, cellular responses including altered clotting factor processing and coagulopathy, organ level effects such as hemorrhage, organism responses with linkages to reduced fitness and mortality, and potential consequences to predator populations. (usgs.gov)
Doses3
  • Until recently, the majority of the research investigating vitamin K's potential for the prevention and treatment of age-associated diseases has been conducted using pharmacological doses of supplemental K1 or MK-4. (vitamindwiki.com)
  • The warfarin doses before vitamin K were not significantly different between the 3 groups and, in fact, the absolute mean dose was lower in the GG group than in the GA or the AA group (3.23 mg, 4.52 mg, and 3.50 mg, respectively). (clotcare.com)
  • The warfarin doses after the addition of vitamin K also were not significantly different (mean daily doses of 4.05 mg, 4.86 mg, and 3.50 mg for GG, GA, and AA, respectively) - and the mean dose for the "resistant" group remained lower than the mean dose for the "average" (GA) group. (clotcare.com)
Production of coagulation proteins1
  • VK, an essential, lipid-soluble vitamin that plays a vital role in the production of coagulation proteins, is found in green, leafy vegetables and in oils, such as soybean, cottonseed, canola, and olive oils. (medscape.com)
Carboxylase1
Deficient1
  • Vitamin K is rarely deficient in a human diet since it is continually recycled in our cells. (com.vn)
Coagulation cascade1
  • Warfarin blocks the function of vitamin K and disrupts the coagulation cascade to reduce the frequency and extent of thrombus formation. (icliniq.com)
Deficiency3
  • Vitamin K (VK) deficiency can occur in any age group but is encountered most often in infancy. (medscape.com)
  • The risk of developing VK deficiency bleeding is 81 times greater in infants who do not receive a vitamin K injection. (medscape.com)
  • Elevated levels of serum vitamin K epoxide in patients is associated with familial multiple coagulation factor deficiency. (com.vn)
Prothrombin2
  • Other vitamin K-dependent factors include prothrombin, factors IX and X, and proteins C and S. (medscape.com)
  • The discovery of vitamin K-dependent factors evolved slowly, after the initial identification of the role of prothrombin in blood clotting 100 years ago. (medscape.com)
Anticoagulation1
  • On the other hand, Warfarin has been a mainstay in anticoagulation therapy for decades, relying on its ability to interfere with vitamin K-dependent clotting factors. (therxadvocates.com)
Active vitamin1
  • Without active vitamin K, these clotting factors cannot function effectively and decrease the ability of the blood to clot. (therxadvocates.com)
Dose2
  • The bottom line of this report is that those with the "resistant" genotype (GG) who typically require a higher dose of warfarin show the greatest fall in the INR (or require the largest upward dose adjustment of warfarin) when daily vitamin K supplementation (150 mcg) is initiated to help stabilize the INR. (clotcare.com)
  • Although a variety of other factors may influence the response to vitamin K supplementation, the mean increase in warfarin dose that was required was 25% for resistant (GG) patients, 8% for GA patients, and 0% for sensitive AA patients following the implementation of daily vitamin K supplementation. (clotcare.com)
Intake1
  • This indicates that current intake (and RDA) values for vitamin K are too low to support proper function of extra-hepatic Gla-proteins. (vitamindwiki.com)
Supplementation3
Form4
  • This leads to the depletion of the reduced form of vitamin K (vitamin KH2). (smpdb.ca)
  • Due to this, vitamin K is unable to be reduced to its active form--hydroquinone (vitamin KH2). (picmonic.com)
  • Whenever each glutamyl residue is carboxylated, the reduced vitamin K is converted to the epoxide form. (medscape.com)
  • Vitamin K epoxide reductase is required to convert the epoxide form of vitamin K back to the reduced form. (medscape.com)
Cardiovascular1
  • The breaking research is revealing a number of roles for vitamin K reaching well beyond coagulation to not only long term cardiovascular and skeletal health, but that of the brain and nervous system, and also for insulin production and sensitivity, and genomic stability / cancer prevention. (vitamindwiki.com)
Human1
  • Sufficiency of vitamin K, as K2 specifically, is gaining recognition as a requirement for long term health in many more areas of human physiology than previously realized. (vitamindwiki.com)
Dependent2
  • Most of these clotting factors are vitamin K dependent proteins, which suggest that reduced vitamin K is essential for activating clotting factors. (hindawi.com)
  • Factor VII is a vitamin K-dependent serine protease glycoprotein (also known as stable factor or proconvertin) with a pivotal role in hemostasis and coagulation. (medscape.com)
Functional1
  • Both the K1 and K2 forms of the vitamin contain a functional napthoquinone ring and an aliphatic side chain. (vitamindwiki.com)
Blood1
  • Vitamin K is essential for blood coagulation. (com.vn)
Levels1
  • It is important to note that an increase in vitamin K levels in the body can promote clotting and reduce the effectiveness of Warfarin. (icliniq.com)