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Phytomenadione

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Phytomenadione
Clinical data
Trade namesMephyton, others
Other namesVitamin K1, phytonadione, phylloquinone, (E)-phytonadione
AHFS/Drugs.comMonograph
Routes of
administration		by mouth, subQ, IM, IV
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
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.001.422 Edit 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 as vitamin K1 or phylloquinone, is a vitamin found in food and used as a dietary supplement.[2][3] As a supplement it is used to treat certain bleeding disorders.[3] This includes in warfarin overdose, vitamin K deficiency, and obstructive jaundice.[3] It is also recommended to prevent and treat vitamin K deficiency bleeding in infants.[3] Use is typically recommended by mouth or injection under the skin.[3] Use by injection into a vein or muscle is recommended only when other routes are not possible.[3] When given by injection benefits are seen within two hours.[3]

Common side effects when given by injection include pain at the site of injection and altered taste.[3] Severe allergic reactions may occur when it is injected into a vein or muscle.[3] It is unclear if use during pregnancy is safe; however, use is likely okay during breastfeeding.[4] It works by supplying a required component for making a number of blood clotting factors.[3] Found sources include green vegetables, vegetable oil, and some fruit.[5]

Phytomenadione was first isolated in 1939.[6] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[7] The wholesale cost in the developing world is about 0.11 to 1.27 USD for a 10 mg vial.[8] In the United States a course of treatment costs less than 25 USD.[9] In 1943 Edward Doisy and Henrik Dam were given a Nobel Prize for its discovery.[6]

Terminology

Phytomenadione is often also called phylloquinone, vitamin K,[10] or phytonadione. Sometimes a distinction is made between phylloquinone, which is considered to be a natural substance, and phytonadione, which is considered to be a synthetic substance.[11]

A stereoisomer of phylloquinone is called vitamin k1 (note the difference in capitalization).[citation needed]

Chemistry

Vitamin K is a fat-soluble vitamin that is stable in air and moisture but decomposes in sunlight. It is a polycyclic aromatic ketone, based on 2-methyl-1,4-naphthoquinone, with a 3-phytyl substituent. It is found naturally in a wide variety of green plants, particularly in leaves, since it functions as an electron acceptor during photosynthesis, forming part of the electron transport chain of photosystem I.[12][13]

The best-known function of vitamin K in animals is as a cofactor in the formation of coagulation factors II (prothrombin), VII, IX, and X by the liver. It is also required for the formation of anticoagulant factors protein C and S. It is commonly used to treat warfarin toxicity, and as an antidote for coumatetralyl.

Vitamin K is required for bone protein formation.

Biosynthesis

File:Updated chem 257.jpg
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:[14][15]

  1. Chorismate is isomerized 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).   

See also

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ Watson, Ronald Ross (2014). Diet and Exercise in Cystic Fibrosis. Academic Press. p. 187. ISBN 9780128005880. Archived from the original on 2016-12-30. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  3. ^ a b c d e f g h i j "Phytonadione". The American Society of Health-System Pharmacists. Archived from the original on 29 December 2016. Retrieved 8 December 2016.
  4. ^ "Phytonadione Use During Pregnancy". Drugs.com. Archived from the original on 29 December 2016. Retrieved 29 December 2016.
  5. ^ "Office of Dietary Supplements – Vitamin K". ods.od.nih.gov. 11 February 2016. Archived from the original on 31 December 2016. Retrieved 30 December 2016.
  6. ^ a b Sneader, Walter (2005). Drug Discovery: A History. John Wiley & Sons. p. 243. ISBN 9780471899792. Archived from the original on 2016-12-30. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  7. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  8. ^ "Vitamin K1". International Drug Price Indicator Guide. Archived from the original on 10 May 2017. Retrieved 8 December 2016.
  9. ^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 229. ISBN 9781284057560. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  10. ^ 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): 1105–17. doi:10.1093/jn/112.6.1105. PMID 7086539.
  11. ^ "Vitamin K". Retrieved 2009-03-18.
  12. ^ Itoh, Shigeru; Iwaki, Masayo (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. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  13. ^ Palace GP, Franke JE, Warden JT (May 1987). "Is phylloquinone an obligate electron carrier in photosystem I?". FEBS Letters. 215 (1): 58–62. doi:10.1016/0014-5793(87)80113-8. PMID 3552735.
  14. ^ Reumann S (2013). "Biosynthesis of vitamin K1 (phylloquinone) by plant peroxisomes and its integration into signaling molecule synthesis pathways". Sub-Cellular Biochemistry. Subcellular Biochemistry. 69. Springer Netherlands: 213–29. doi:10.1007/978-94-007-6889-5_12. ISBN 9789400768888. PMID 23821151.
  15. ^ 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): 5599–603. doi:10.1073/pnas.0900738106. PMC 2660889. PMID 19321747.
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