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Phytomenadione

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Phytomenadione
Vitamin K1.png
Names
Trade namesMephyton, others
Other namesVitamin K1, phytonadione, phylloquinone, (E)-phytonadione
Clinical data
Drug classVitamin
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
use
by mouth, subQ, IM, IV
Defined daily dose20 mg[1]
External links
AHFS/Drugs.comMonograph
Legal
Legal status
Chemical and physical data
FormulaC31H46
Molar mass418.709 g·mol−1
3D model (JSmol)

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 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] In 1943 Edward Doisy and Henrik Dam were given a Nobel Prize for its discovery.[6] It is on the World Health Organization's List of Essential Medicines.[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]

Medical uses

Dosage

The defined daily dose is 20 milligrams by injection or by mouth.[1] For prevention of bleeding in the newborn it is used at a dose of 0.5 mg by injection for those who weight less than 1.5 kg and 1 mg for those who weight more.[10] For treatment of bleeding in the newborn it is used at a dose of 1 mg three times per day.[10]

Terminology

Phytomenadione is often also called phylloquinone, vitamin K,[11] 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.[12]

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.[13][14]

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

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:[15][16]

  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. 1.0 1.1 "WHOCC - ATC/DDD Index". www.whocc.no. Retrieved 4 September 2020.
  2. Watson RR (2014). Diet and Exercise in Cystic Fibrosis. Academic Press. p. 187. ISBN 9780128005880. Archived from the original on 2016-12-30.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 "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. 6.0 6.1 Sneader W (2005). Drug Discovery: A History. John Wiley & Sons. p. 243. ISBN 9780471899792. Archived from the original on 2016-12-30.
  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 R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 229. ISBN 9781284057560.
  10. 10.0 10.1 "PHYTOMENADIONE = VITAMIN K1 injectable - Essential drugs". medicalguidelines.msf.org. Retrieved 4 September 2020.
  11. 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.
  12. "Vitamin K". Retrieved 2009-03-18.
  13. 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.
  14. 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.
  15. Reumann S (2013). "Biosynthesis of vitamin K1 (phylloquinone) by plant peroxisomes and its integration into signaling molecule synthesis pathways". Sub-Cellular Biochemistry. Subcellular Biochemistry. Springer Netherlands. 69: 213–29. doi:10.1007/978-94-007-6889-5_12. ISBN 9789400768888. PMID 23821151.
  16. 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.

External links

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