DT-Web

DB01022 - Phytonadione


Identification
Name Phytonadione
Accession Number DB01022 (APRD00464)
Type small molecule
Description Phytonadione is often called vitamin K1. It is a fat-soluble vitamin that is stable to air and moisture but decomposes in sunlight. It is found naturally in a wide variety of green plants. Phylloquinone is also an antidote for coumatetralyl. Vitamin K is needed for the posttranslational modification of certain proteins, mostly required for blood coagulation.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 450.6957
Groups approved
Monoisotopic Weight 450.349780716
Pharmacology
Indication For the treatment of haemorrhagic conditions in infants, antidote for coumarin anticoagulants in hypoprothrombinaemia
Mechanism of action Vitamin K is an essential cofactor for the gamma-carboxylase enzymes which catalyze the posttranslational gamma-carboxylation of glutamic acid residues in inactive hepatic precursors of coagulation factors II (prothrombin), VII, IX and X. Gamma-carboxylation converts these inactive precursors into active coagulation factors which are secreted by hepatocytes into the blood. Supplementing with Phytonadione results in a relief of vitamin K deficiency symptoms which include easy bruisability, epistaxis, gastrointestinal bleeding, menorrhagia and hematuria.
Absorption Oral phytonadione is adequately absorbed from the gastrointestinal tract only if bile salts are present. After absorption, phytonadione is initially concentrated in the liver, but the concentration declines rapidly. Very little vitamin K accumulates in tissues.
Protein binding Not Available
Biotransformation Not Available
Route of elimination Almost no free unmetabolized vitamin K appears in bile or urine.
Toxicity The intravenous LD50 of phytonadione in the mouse is 41.5 and 52 mL/kg for the 0.2% and 1% concentrations, respectively.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Warfarin Phytonadione (vitamin K) may antagonize the anticoagulant effects of warfarin. Monitor for changes in prothrombin time if phytonadione intake (either via supplements or vitamin K-rich foods) is increased or decreased.
Food Interactions Not Available

Targets


Vitamin K-dependent gamma-carboxylase
Name Vitamin K-dependent gamma-carboxylase
Gene Name GGCX
Pharmacological action yes
Actions inducer
References
  • Morris DP, Soute BA, Vermeer C, Stafford DW: Characterization of the purified vitamin K-dependent gamma-glutamyl carboxylase. J Biol Chem. 1993 Apr 25;268(12):8735-42. - Pubmed
  • Tuan RS: Vitamin K-dependent gamma-glutamyl carboxylase activity in the chick embryonic chorioallantoic membrane. J Biol Chem. 1979 Feb 25;254(4):1356-64. - Pubmed
  • Reedstrom CK, Suttie JW: Comparative distribution, metabolism, and utilization of phylloquinone and menaquinone-9 in rat liver. Proc Soc Exp Biol Med. 1995 Sep;209(4):403-9. - Pubmed
  • Tasatargil A, Cadir B, Dalaklioglu S, Yurdakonar E, Caglar S, Turkay C: Effects of vitamin K1 supplementation on vascular responsiveness and oxidative stress in a rat femoral osteotomy model. Cell Biochem Funct. 2007 Sep-Oct;25(5):485-90. - Pubmed
  • Olson RE: The function and metabolism of vitamin K. Annu Rev Nutr. 1984;4:281-337. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.6933
Osteocalcin
Name Osteocalcin
Gene Name BGLAP
Pharmacological action unknown
Actions agonist
References
  • Sato Y, Tsuru T, Oizumi K, Kaji M: Vitamin K deficiency and osteopenia in disuse-affected limbs of vitamin D-deficient elderly stroke patients. Am J Phys Med Rehabil. 1999 Jul-Aug;78(4):317-22. - Pubmed
  • Schurgers LJ, Dissel PE, Spronk HM, Soute BA, Dhore CR, Cleutjens JP, Vermeer C: Role of vitamin K and vitamin K-dependent proteins in vascular calcification. Z Kardiol. 2001;90 Suppl 3:57-63. - Pubmed
  • Vermeer C, Wolf J, Craciun AM, Knapen MH: Bone markers during a 6-month space flight: effects of vitamin K supplementation. J Gravit Physiol. 1998 Oct;5(2):65-9. - Pubmed
  • Askim M: [Vitamin K in the Norwegian diet and osteoporosis] Tidsskr Nor Laegeforen. 2001 Sep 20;121(22):2614-6. - Pubmed
  • Kawana K, Takahashi M, Hoshino H, Kushida K: Circulating levels of vitamin K1, menaquinone-4, and menaquinone-7 in healthy elderly Japanese women and patients with vertebral fractures and patients with hip fractures. Endocr Res. 2001 Aug;27(3):337-43. - Pubmed
DTHybrid score 0.511

Predictions


Id Partner name Gene Name Score
239 Coagulation factor X F10 0.1153
54 Prothrombin F2 0.0869
369 Coagulation factor VII F7 0.0795
5142 Protein-tyrosine-phosphatase PPI 0.0747
19 Coagulation factor VIII F8 0.0706
6315 V-type proton ATPase subunit B, brain isoform ATP6V1B2 0.0665
1654 Interleukin-1 beta IL1B 0.061
4218 Ribonucleoside-diphosphate reductase M2 subunit RRM2 0.0568
566 Serotransferrin TF 0.0535
1334 Tissue factor pathway inhibitor TFPI 0.0521
1245 Vitamin K-dependent protein S PROS1 0.0515
3831 Low-density lipoprotein receptor-related protein 1 LRP1 0.0411
2139 Tissue factor F3 0.0381
4081 Vitamin K epoxide reductase complex subunit 1-like protein 1 VKORC1L1 0.0363
3851 Serine protease hepsin HPN 0.0363
604 Vitamin K-dependent protein Z PROZ 0.0363
400 Coagulation factor IX F9 0.0358
5461 Coagulation factor IX F9 0.0358
422 Vitamin K-dependent protein C PROC 0.0303
1959 Platelet factor 4 PF4 0.0299
3865 Serpin B6 SERPINB6 0.0299
1986 Ceruloplasmin CP 0.0299
1547 Coagulation factor XI F11 0.0269
3833 Plasma serine protease inhibitor SERPINA5 0.026
46 Coagulation factor V F5 0.0236
2021 Thrombomodulin THBD 0.0235
2072 Endothelial protein C receptor PROCR 0.023
787 Vitamin K epoxide reductase complex subunit 1 VKORC1 0.023
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0215
3917 Methylenetetrahydrofolate reductase MTHFR 0.0209
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0203
267 Plasminogen activator inhibitor 1 SERPINE1 0.0196
6020 Aldehyde oxidase AOX1 0.0192
3947 Xanthine dehydrogenase/oxidase XDH 0.0176
5718 Cytochrome P450 2A6 CYP2A6 0.0138
6024 Cytochrome P450 1A1 CYP1A1 0.0131
6013 Cytochrome P450 2E1 CYP2E1 0.0124
4200 Cytochrome P450 1A2 CYP1A2 0.0108
4024 Mitochondrial glutamate carrier 2 SLC25A18 0.0042
4025 Mitochondrial glutamate carrier 1 SLC25A22 0.0042
4022 Glutamate--ammonia ligase domain-containing protein 1 LGSN 0.0042
4019 Excitatory amino acid transporter 4 SLC1A6 0.0042
919 Glutamate receptor, ionotropic kainate 4 GRIK4 0.0042
920 Glutamate receptor, ionotropic kainate 5 GRIK5 0.0042
4026 Aspartyl aminopeptidase DNPEP 0.0042
4021 Probable glutamyl-tRNA synthetase, mitochondrial EARS2 0.0042
4023 N-acetylglutamate synthase, mitochondrial NAGS 0.0042
1912 Excitatory amino acid transporter 1 SLC1A3 0.0042
4016 Excitatory amino acid transporter 5 SLC1A7 0.0042
1047 Excitatory amino acid transporter 2 SLC1A2 0.0042
922 Glutamate receptor 4 GRIA4 0.0042
664 Glutamate decarboxylase 2 GAD2 0.0042
3890 Glutamate decarboxylase 2 GAD2 0.0042
926 Metabotropic glutamate receptor 7 GRM7 0.0042
924 Glutamate receptor, ionotropic kainate 3 GRIK3 0.0042
915 Delta 1-pyrroline-5-carboxylate synthetase ALDH18A1 0.0042
927 Metabotropic glutamate receptor 8 GRM8 0.0042
925 Metabotropic glutamate receptor 4 GRM4 0.0042
4020 Glutamyl aminopeptidase ENPEP 0.0042
4018 Glutamate receptor delta-2 subunit GRID2 0.0042
4027 Glutamate receptor delta-1 subunit GRID1 0.0042
4017 5-oxoprolinase OPLAH 0.0042
917 Glutaminase kidney isoform, mitochondrial GLS 0.0036
355 GMP synthase [glutamine-hydrolyzing] GMPS 0.0036
4353 GMP synthase [glutamine-hydrolyzing] guaA 0.0036
3991 Glutamine-dependent NAD(+) synthetase NADSYN1 0.0036
3984 Probable glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial PET112L 0.0036
5 Glutaminase liver isoform, mitochondrial GLS2 0.0036
665 Phosphoserine aminotransferase PSAT1 0.0036
4652 Phosphoserine aminotransferase serC 0.0036
668 Glutamate--cysteine ligase regulatory subunit GCLM 0.0036
801 Kynurenine/alpha-aminoadipate aminotransferase mitochondrial AADAT 0.0036
3982 Phosphoribosylformylglycinamidine synthase PFAS 0.0036
5261 Phosphoribosylformylglycinamidine synthase purL 0.0036
3895 Kynurenine--oxoglutarate transaminase 3 CCBL2 0.0036
420 Glutamate decarboxylase 1 GAD1 0.0036
3900 Glutamate decarboxylase 1 GAD1 0.0036
830 Glutamate dehydrogenase 2, mitochondrial GLUD2 0.0035
382 Glutamate receptor, ionotropic kainate 1 GRIK1 0.0035
625 Glutamate carboxypeptidase 2 FOLH1 0.0033
186 Glutamate--cysteine ligase catalytic subunit GCLC 0.0033
916 Metabotropic glutamate receptor 1 GRM1 0.0033
3877 Growth-inhibiting protein 18 GIG18 0.0033
1671 Excitatory amino acid transporter 3 SLC1A1 0.0033
923 Glutamate receptor 3 GRIA3 0.0032
763 Tyrosine aminotransferase TAT 0.0031
5493 Tyrosine aminotransferase Not Available 0.0031
773 Folylpolyglutamate synthase, mitochondrial FPGS 0.0031
914 Formimidoyltransferase-cyclodeaminase FTCD 0.0031
735 Alanine aminotransferase 1 GPT 0.0031
3904 Alanine aminotransferase 2 GPT2 0.0031
426 Aspartate aminotransferase, mitochondrial GOT2 0.0031
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0031
505 Glutamate [NMDA] receptor subunit epsilon-3 GRIN2C 0.003
201 Glutamate dehydrogenase 1, mitochondrial GLUD1 0.003
83 Alpha-aminoadipic semialdehyde synthase, mitochondrial AASS 0.003
586 Aspartate aminotransferase, cytoplasmic GOT1 0.0029
242 Asparagine synthetase [glutamine-hydrolyzing] ASNS 0.0029
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0029
210 Bifunctional aminoacyl-tRNA synthetase [Includes: Glutamyl-tRNA synthetase EPRS 0.0029
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0028
705 Glutamate receptor 1 GRIA1 0.0028
574 Branched-chain-amino-acid aminotransferase, cytosolic BCAT1 0.0027
795 Branched-chain-amino-acid aminotransferase, mitochondrial BCAT2 0.0027
33 Cystine/glutamate transporter SLC7A11 0.0027
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.0027
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0027
3426 Glutamine synthetase glnA 0.0027
3987 Glutamine synthetase GLUL 0.0027
280 4-aminobutyrate aminotransferase, mitochondrial ABAT 0.0026
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0022
918 Glutamate receptor, ionotropic kainate 2 GRIK2 0.0022
738 Monocarboxylate transporter 1 SLC16A1 0.0021
6151 Monocarboxylate transporter 10 SLC16A10 0.002
921 Glutamate receptor 2 GRIA2 0.0019
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