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Phytomenadione

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Chemical compound

Pharmaceutical compound
Phytomenadione
Clinical data
Trade namesMephyton, Hemophyt, others
Other namesVitamin K1, phytonadione, phylloquinone, (E)-phytonadione
AHFS/Drugs.comMonograph
License data
Routes of
administration
By mouth,subcutaneous,intramuscular,intravenous
ATC code
Legal status
Legal status
Identifiers
  • 2-methyl-3-[(E,7R,11R)-3,7,11,15-tetramethylhexadec-2-enyl]naphthalene-1,4-dione
CAS Number
PubChemCID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard(EPA)
ECHA InfoCard100.001.422Edit this at Wikidata
Chemical and physical data
FormulaC31H46O2
Molar mass450.707 g·mol−1
3D model (JSmol)
  • CC1=C(C(=O)c2ccccc2C1=O)C/C=C(\C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C
  • InChI=1S/C31H46O2/c1-22(2)12-9-13-23(3)14-10-15-24(4)16-11-17-25(5)20-21-27-26(6)30(32)28-18-7-8-19-29(28)31(27)33/h7-8,18-20,22-24H,9-17,21H2,1-6H3/b25-20+/t23-,24-/m1/s1 checkY
  • Key:MBWXNTAXLNYFJB-NKFFZRIASA-N

Phytomenadione, also known asvitamin K1,phylloquinone, orphytonadione, is avitamin found in food and used as adietary supplement.[6][7] It is on theWorld Health Organization's List of Essential Medicines.[8]

It is used to treat certainbleeding disorders,[7] includingwarfarin overdose,vitamin K deficiency, andobstructive jaundice.[7] Use is typically recommended by mouth, intramuscular injection orinjection under the skin.[7] When given by injection benefits are seen within two hours.[7] It is also recommended for preventing and treatingvitamin K deficiency bleeding in infants.[7] Many countries in the world choose intramuscular injections in newborn to keep them safe from vitamin K deficiency bleeding. It is considered a safe treatment and saves many children from death and severe neurologic deficit every year.[9]

Side effects when given by injection may include pain at the site of injection.[7] Severeallergic reactions may occur when it is injected into a vein or muscle, but this has mainly happened when large doses of a certain type of supplement containingcastor oil were given intravenously.[10] Use during pregnancy is considered safe,[11] use is also likely okay duringbreastfeeding.[12] It works by supplying a required component for making a number ofblood clotting factors.[7] Food sources includegreen vegetables, vegetable oil, and some fruit.[13]

Phytomenadione was first isolated in 1939.[14] In 1943Edward Doisy andHenrik Dam were given aNobel Prize for its discovery.[14]

Terminology

[edit]

Phytomenadione is often also called phylloquinone,[15] vitamin K,[16] or phytonadione.[15]

Medical uses

[edit]
See also:Vitamin K § Medical uses (the section nearly only covers Vitamin K1, i.e. this compound.)

It is used to treat certainbleeding disorders,[7] includingwarfarin overdose (also overdose of similar compounds such ascoumatetralyl),vitamin K deficiency, andobstructive jaundice.[7] It is used to prevent and treatvitamin K deficiency bleeding in infants.[7]

Chemistry

[edit]

Vitamin K is a fat-soluble vitamin that is stable in air and moisture but decomposes in sunlight.[17] K1 is apolycyclicaromaticketone, based on 2-methyl-1,4-naphthoquinone, with a 3-phytylsubstituent. It is found naturally in a wide variety of green plants, particularly in leaves, since it functions as an electron acceptor duringphotosynthesis, forming part of the electron transport chain ofphotosystem I.[18][19]

Biological function

[edit]
Main article:vitamin K

Animals

[edit]
This sectionneeds additional citations forverification. Please helpimprove this article byadding citations to reliable sources in this section. Unsourced material may be challenged and removed.(March 2024) (Learn how and when to remove this message)

The best-known function of vitamin K in animals is as a cofactor in the formation ofcoagulation factors II (prothrombin), VII, IX, and X by the liver. It is also required for the formation of anticoagulant factors protein C and S. Vitamin K is required for bone protein formation.

In terms of distribution, phylloquinone typically occurs in higher levels in the liver, heart and pancreas, but in lower levels in the brain, kidneys, and lungs.[20]

Plants and cyanobacteria

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Vitamin K1 is required for plantphotosynthesis, where it participates in thePhotosystem Ielectron transport chain.[21]

Biosynthesis

[edit]
The biosynthesis of vitamin K1 via the transformation of chorismate occurs in nine steps.

Vitamin K1 is synthesized from chorismate, a compound produced from shikimate via the shikimate pathway. The conversion of chorismate to vitamin K1 comprises a series of nine steps:[22][23][24]

  1. Chorismate isisomerized to isochorismate by isochorismate synthase, or MenF (menaquinone enzyme).
  2. Addition of 2-oxoglutarate to isochorismate by PHYLLO, a multifunctional protein comprising three different enzymatic activities (MenD, H, and C).
  3. Elimination of pyruvate by PHYLLO.
  4. Aromatization to yield o-succinyl benzoate by PHYLLO.
  5. O-succinylbenzoate activation to corresponding CoA ester by MenE.
  6. Naphthoate ring formation by naphthoate synthase (MenB/NS).
  7. Thiolytic release of CoA by a thioesterase (MenH).
  8. Attachment of phytol chain to the naphthoate ring (MenA/ABC4).
  9. Methylation of the precursor at position 3 (MenG).

Veterinary uses

[edit]

In Canada, phytomenadione (Hemophyt) isindicated for the treatment of anticoagulant poisoning in dogs.[2][3]

References

[edit]
  1. ^"FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)".nctr-crs.fda.gov.FDA. Retrieved22 October 2023.
  2. ^ab"Notice: Multiple additions to the Prescription Drug List (PDL) [2023-08-30]".Health Canada. 26 October 2023. Retrieved3 January 2024.
  3. ^ab"Hemophyt Monograph"(PDF).Health Canada. 24 February 2023.
  4. ^"Phytonadione tablet".DailyMed. 3 December 2024. Retrieved8 January 2025.
  5. ^"Phytonadione injection, emulsion".DailyMed. 12 July 2024. Retrieved8 January 2025.
  6. ^Watson RR (2014).Diet and Exercise in Cystic Fibrosis. Academic Press. p. 187.ISBN 9780128005880.Archived from the original on 30 December 2016.
  7. ^abcdefghijk"Phytonadione". The American Society of Health-System Pharmacists.Archived from the original on 29 December 2016. Retrieved8 December 2016.
  8. ^World Health Organization (2023).The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization.hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  9. ^Furman L (27 July 2018)."American Academy of Pediatrics on vitamin k in the newborn period".
  10. ^Riegert-Johnson DL, Volcheck GW (October 2002). "The incidence of anaphylaxis following intravenous phytonadione (vitamin K1): a 5-year retrospective review".Annals of Allergy, Asthma & Immunology.89 (4):400–406.doi:10.1016/S1081-1206(10)62042-X.PMID 12392385.
  11. ^Bailey B (February 2003). "Are there teratogenic risks associated with antidotes used in the acute management of poisoned pregnant women?".Birth Defects Research. Part A, Clinical and Molecular Teratology.67 (2):133–140.doi:10.1002/bdra.10007.PMID 12769509.
  12. ^"Phytonadione Use During Pregnancy".Drugs.com.Archived from the original on 29 December 2016. Retrieved29 December 2016.
  13. ^"Vitamin K".Office of Dietary Supplements. U.S. National Institutes of Health. 11 February 2016.Archived from the original on 31 December 2016. Retrieved30 December 2016.
  14. ^abSneader W (2005).Drug Discovery: A History. John Wiley & Sons. p. 243.ISBN 9780471899792.Archived from the original on 30 December 2016.{{cite book}}: CS1 maint: overridden setting (link)
  15. ^ab"Vitamin K Substances and Animal Feed".U.S. Food and Drug Administration. 24 October 2024. Retrieved8 January 2025.
  16. ^Haroon Y, Shearer MJ, Rahim S, Gunn WG, McEnery G, Barkhan P (June 1982). "The content of phylloquinone (vitamin K1) in human milk, cows' milk and infant formula foods determined by high-performance liquid chromatography".The Journal of Nutrition.112 (6):1105–1117.doi:10.1093/jn/112.6.1105.PMID 7086539.
  17. ^Institute of Medicine (US) Panel on Micronutrients."Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc". Washington (DC): National Academies Press (US). Retrieved25 November 2021 – via NCBI.
  18. ^Itoh S, Iwaki M (1989)."Vitamin K1 (Phylloquinone) Restores the Turnover of FeS centers of Ether-extracted Spinach PSI Particles".FEBS Letters.243 (1):47–52.doi:10.1016/0014-5793(89)81215-3.S2CID 84602152.
  19. ^Palace GP, Franke JE, Warden JT (May 1987)."Is phylloquinone an obligate electron carrier in photosystem I?".FEBS Letters.215 (1):58–62.Bibcode:1987FEBSL.215...58P.doi:10.1016/0014-5793(87)80113-8.PMID 3552735.S2CID 42983611.
  20. ^Bus K, Szterk A (December 2021)."Relationship between Structure and Biological Activity of Various Vitamin K Forms".Foods.10 (12): 3136.doi:10.3390/foods10123136.PMC 8701896.PMID 34945687.
  21. ^Basset GJ, Latimer S, Fatihi A, Soubeyrand E, Block A (2017). "Phylloquinone (Vitamin K1): Occurrence, Biosynthesis and Functions".Mini Reviews in Medicinal Chemistry.17 (12):1028–1038.doi:10.2174/1389557516666160623082714.PMID 27337968.
  22. ^Reumann S (2013). "Biosynthesis of vitamin K1 (phylloquinone) by plant peroxisomes and its integration into signaling molecule synthesis pathways".Peroxisomes and their Key Role in Cellular Signaling and Metabolism. Subcellular Biochemistry. Vol. 69. Springer Netherlands. pp. 213–29.doi:10.1007/978-94-007-6889-5_12.ISBN 9789400768888.PMID 23821151.
  23. ^Widhalm JR, van Oostende C, Furt F, Basset GJ (April 2009)."A dedicated thioesterase of the Hotdog-fold family is required for the biosynthesis of the naphthoquinone ring of vitamin K1".Proceedings of the National Academy of Sciences of the United States of America.106 (14):5599–5603.Bibcode:2009PNAS..106.5599W.doi:10.1073/pnas.0900738106.PMC 2660889.PMID 19321747.
  24. ^Van Oostende C, Widhalm JR, Furt F, Ducluzeau AL, Basset GJ (2011)."Vitamin K1 (Phylloquinone)".Advances in Botanical Research.59:229–261.doi:10.1016/B978-0-12-385853-5.00001-5.ISBN 9780123858535.

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