Not to confuse with menaquinone-3, aka MK-3, a version of vitamin K2 series having 3 isoprene groups
This article is missing information about drugbox or more Chembox Pharmacology. Please expand the article to include this information. Further details may exist on the talk page.(January 2021)
Menadione is also a circulating form of vitamin K, produced in small amounts (1–5%) after intestinal absorption of K1 and K2. This circulation explains the uneven tissue distribution of MK-4, especially since menadione can penetrate the blood–brain barrier. The cleavage enzyme is yet to be identified. As K3 is known to be toxic in large amounts, researchers speculate that the cleavage process is closely regulated.[5]
Terminologyedit
The compound is variously known as vitamin K3[6] and provitamin K3.[7] Proponents of the latter name generally argue that the compound is not a real vitamin due to its artificial status (prior to its identification as a circulating intermediate) and its lack of a 3-methyl side chain preventing it from exert all the functions (specifically, it cannot act as a cofactor for GGCXin vitro)[8] of the K vitamins.
Usesedit
The menadione core is apparent in the structure of vitamin K.
It is an intermediate in the chemical synthesis of vitamin K by first reduction to the diolmenadiol, which is susceptible to coupling to the phytol.[9] It is a useful intermediate for organic synthesis in general, as it can be made and modified in a number of ways.[10]
Menadione can be used to generate reactive oxygen species to perform flow cytometry analysis on. It can also be used in microbiological evaluation to, for example, detect fastidious microorganisms.[11]
Animal feededit
In the United States, menadione is used in various types of animal feed and is described as having a history of safe use for this purpose, being used in poultry feed prior to 1958.[12]
Low-dose menadione is used as an inexpensive micronutrient for livestock in many countries. Forms of menadione are also included in some pet foods in developed countries as a source of vitamin K. These doses have yielded no reported cases of toxicity from menadione in livestock or pets. Although handling may be hazardous, the European Food Safety Authority found in 2013 that it is an effective source of vitamin K in animal nutrition that does not pose a risk to the environment.[13]
Human useedit
Despite the fact that it can serve as a precursor to various types of vitamin K, menadione is generally not used as a nutritional supplement in economically developed countries. Menadione for human use at pharmaceutical strength is available in some countries with large lower income populations, such as India.[2] The typical daily dose is 10 mg oral or 2 mg parenteral.[14] It is used in the treatment of hypoprothrombinemia outside of the United States.[2]
Toxicologyedit
Menadione is not believed to be carcinogenic.[15] K3 can cause generation of reactive oxygen species (ROS) by redox cycling and arylation of thiols using its reactive 3-position.[5] ROS generation explains various toxic effects of excessive menadione, including DNA damage and cell death,[15] or on a whole-animal level, cardiac and renal toxicity in rats.[16]
^ abc"Menadione drug information". DrugsUpdate India.
^ abHirota, Yoshihisa; Tsugawa, Naoko; Nakagawa, Kimie; Suhara, Yoshitomo; Tanaka, Kiyoshi; Uchino, Yuri; Takeuchi, Atsuko; Sawada, Natsumi; Kamao, Maya; Wada, Akimori; Okitsu, Takashi (2013-11-15). "Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating precursor of tissue menaquinone-4 (vitamin K2) in rats". The Journal of Biological Chemistry. 288 (46): 33071–33080. doi:10.1074/jbc.M113.477356. ISSN 1083-351X. PMC3829156. PMID 24085302.
^Castro FA, Mariani D, Panek AD, Eleutherio EC, Pereira MD (2008). Fox (ed.). "Cytotoxicity mechanism of two naphthoquinones (menadione and plumbagin) in Saccharomyces cerevisiae". PLOS ONE. 3 (12): e3999. Bibcode:2008PLoSO...3.3999C. doi:10.1371/journal.pone.0003999. PMC2600608. PMID 19098979.
^ abcShearer, Martin J.; Newman, Paul (March 2014). "Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis". Journal of Lipid Research. 55 (3): 345–362. doi:10.1194/jlr.R045559. ISSN 0022-2275. PMC3934721. PMID 24489112.
^Scott GK, Atsriku C, Kaminker P, Held J, Gibson B, Baldwin MA, Benz CC (September 2005). "Vitamin K3 (menadione)-induced oncosis associated with keratin 8 phosphorylation and histone H3 arylation". Molecular Pharmacology. 68 (3): 606–15. doi:10.1124/mol.105.013474. PMID 15939799. S2CID 19076885.
^"Vitamin K". Linus Pauling Institute. 2014-04-22. Retrieved 2021-01-28.
^Buitenhuis, HC; Soute, BA; Vermeer, C (16 May 1990). "Comparison of the vitamins K1, K2 and K3 as cofactors for the hepatic vitamin K-dependent carboxylase". Biochimica et Biophysica Acta (BBA) - General Subjects. 1034 (2): 170–5. doi:10.1016/0304-4165(90)90072-5. PMID 2112953.
^Weber F, Rüttimann A (2012). "Vitamin K". Ullmann's Encyclopedia Of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.o27_o08. S2CID 86263542.
^de Souza, AS; Ribeiro, RCB; Costa, DCS; Pauli, FP; Pinho, DR; de Moraes, MG; da Silva, FC; Forezi, LDSM; Ferreira, VF (2022). "Menadione: a platform and a target to valuable compounds synthesis". Beilstein Journal of Organic Chemistry. 18: 381–419. doi:10.3762/bjoc.18.43. PMC9039524. PMID 35529893.
^"Menadione". Sigma-Aldrich. Retrieved 2 February 2023.
^"Vitamin K Substances and Animal Feed". FDA. 2 April 2021.
^EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) (January 2014). "Scientific Opinion on the safety and efficacy of vitamin K3 (menadione sodium bisulphite and menadione nicotinamide bisulphite) as a feed additive for all animal species". EFSA Journal. 12 (1): 3532. doi:10.2903/j.efsa.2014.3532.
^ abHassan, Ghada S. (2013). "Menadione". Profiles of Drug Substances, Excipients and Related Methodology. Vol. 38. pp. 227–313. doi:10.1016/B978-0-12-407691-4.00006-X. ISBN9780124076914. PMID 23668406. S2CID 242264898.
^Chiou, TJ; Zhang, J; Ferrans, VJ; Tzeng, WF (31 December 1997). "Cardiac and renal toxicity of menadione in rat". Toxicology. 124 (3): 193–202. doi:10.1016/s0300-483x(97)00162-5. PMID 9482121.
External linksedit
Menadione in the Pesticide Properties DataBase (PPDB)
May 01, 2024
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Not to confuse with menaquinone 3 aka MK 3 a version of vitamin K2 series having 3 isoprene groups This article is missing information about drugbox or more Chembox Pharmacology Please expand the article to include this information Further details may exist on the talk page January 2021 Menadione is a natural 3 organic compound with the formula C6H4 CO 2C2H CH3 It is an analog of 1 4 naphthoquinone with a methyl group in the 2 position 4 It is sometimes called vitamin K3 Use is allowed as a nutritional supplement in animal feed because of its vitamin K activity Menadione 1 Names Preferred IUPAC name 2 Methylnaphthalene 1 4 dione Other names Menaphthone Vitamin K3 b Methyl 1 4 naphthoquinone 2 Methyl 1 4 naphthodione 2 Methyl 1 4 naphthoquinone Identifiers CAS Number 58 27 5 Y 3D model JSmol Interactive image ChEBI CHEBI 28869 N ChEMBL ChEMBL590 Y ChemSpider 3915 Y DrugBank DB00170 N ECHA InfoCard 100 000 338 KEGG D02335 Y PubChem CID 4055 UNII 723JX6CXY5 Y CompTox Dashboard EPA DTXSID4021715 InChI InChI 1S C11H8O2 c1 7 6 10 12 8 4 2 3 5 9 8 11 7 13 h2 6H 1H3 YKey MJVAVZPDRWSRRC UHFFFAOYSA N YInChI 1 C11H8O2 c1 7 6 10 12 8 4 2 3 5 9 8 11 7 13 h2 6H 1H3Key MJVAVZPDRWSRRC UHFFFAOYAY SMILES O C 2c1c cccc1 C O C C 2 C Properties Chemical formula C 11H 8O 2 Molar mass 172 183 g mol 1 Appearance Bright yellow crystals Density 1 225g cm3 Melting point 105 to 107 C 221 to 225 F 378 to 380 K Solubility in water Insoluble Pharmacology ATC code B02BA02 WHO Pregnancycategory Contraindicated India 2 Routes ofadministration OralIntravenousIntramuscular Legal status Generally Rx or withdrawn for human use approved in animal feed Hazards Flash point 113 8 C 236 8 F 386 9 K Lethal dose or concentration LD LC LD50 median dose 0 5 g kg oral mouse Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references Contents 1 Biochemistry 2 Terminology 3 Uses 3 1 Animal feed 3 2 Human use 4 Toxicology 5 References 6 External linksBiochemistry editMenadione is converted to vitamin K2 specifically MK 4 by the prenyltransferase action of vertebrate UBIAD1 3 This reaction requires the hydroquinone reduced form of K3 menadiol produced by NQO1 5 Menadione is also a circulating form of vitamin K produced in small amounts 1 5 after intestinal absorption of K1 and K2 This circulation explains the uneven tissue distribution of MK 4 especially since menadione can penetrate the blood brain barrier The cleavage enzyme is yet to be identified As K3 is known to be toxic in large amounts researchers speculate that the cleavage process is closely regulated 5 Terminology editThe compound is variously known as vitamin K3 6 and provitamin K3 7 Proponents of the latter name generally argue that the compound is not a real vitamin due to its artificial status prior to its identification as a circulating intermediate and its lack of a 3 methyl side chain preventing it from exert all the functions specifically it cannot act as a cofactor for GGCX in vitro 8 of the K vitamins Uses edit nbsp The menadione core is apparent in the structure of vitamin K It is an intermediate in the chemical synthesis of vitamin K by first reduction to the diol menadiol which is susceptible to coupling to the phytol 9 It is a useful intermediate for organic synthesis in general as it can be made and modified in a number of ways 10 Menadione can be used to generate reactive oxygen species to perform flow cytometry analysis on It can also be used in microbiological evaluation to for example detect fastidious microorganisms 11 Animal feed edit In the United States menadione is used in various types of animal feed and is described as having a history of safe use for this purpose being used in poultry feed prior to 1958 12 Low dose menadione is used as an inexpensive micronutrient for livestock in many countries Forms of menadione are also included in some pet foods in developed countries as a source of vitamin K These doses have yielded no reported cases of toxicity from menadione in livestock or pets Although handling may be hazardous the European Food Safety Authority found in 2013 that it is an effective source of vitamin K in animal nutrition that does not pose a risk to the environment 13 Human use edit Despite the fact that it can serve as a precursor to various types of vitamin K menadione is generally not used as a nutritional supplement in economically developed countries Menadione for human use at pharmaceutical strength is available in some countries with large lower income populations such as India 2 The typical daily dose is 10 mg oral or 2 mg parenteral 14 It is used in the treatment of hypoprothrombinemia outside of the United States 2 Toxicology editMenadione is not believed to be carcinogenic 15 K3 can cause generation of reactive oxygen species ROS by redox cycling and arylation of thiols using its reactive 3 position 5 ROS generation explains various toxic effects of excessive menadione including DNA damage and cell death 15 or on a whole animal level cardiac and renal toxicity in rats 16 References edit The Merck Index 11th Edition 5714 a b c Menadione drug information DrugsUpdate India a b Hirota Yoshihisa Tsugawa Naoko Nakagawa Kimie Suhara Yoshitomo Tanaka Kiyoshi Uchino Yuri Takeuchi Atsuko Sawada Natsumi Kamao Maya Wada Akimori Okitsu Takashi 2013 11 15 Menadione vitamin K3 is a catabolic product of oral phylloquinone vitamin K1 in the intestine and a circulating precursor of tissue menaquinone 4 vitamin K2 in rats The Journal of Biological Chemistry 288 46 33071 33080 doi 10 1074 jbc M113 477356 ISSN 1083 351X PMC 3829156 PMID 24085302 Castro FA Mariani D Panek AD Eleutherio EC Pereira MD 2008 Fox ed Cytotoxicity mechanism of two naphthoquinones menadione and plumbagin in Saccharomyces cerevisiae PLOS ONE 3 12 e3999 Bibcode 2008PLoSO 3 3999C doi 10 1371 journal pone 0003999 PMC 2600608 PMID 19098979 a b c Shearer Martin J Newman Paul March 2014 Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK 4 biosynthesis Journal of Lipid Research 55 3 345 362 doi 10 1194 jlr R045559 ISSN 0022 2275 PMC 3934721 PMID 24489112 Scott GK Atsriku C Kaminker P Held J Gibson B Baldwin MA Benz CC September 2005 Vitamin K3 menadione induced oncosis associated with keratin 8 phosphorylation and histone H3 arylation Molecular Pharmacology 68 3 606 15 doi 10 1124 mol 105 013474 PMID 15939799 S2CID 19076885 Vitamin K Linus Pauling Institute 2014 04 22 Retrieved 2021 01 28 Buitenhuis HC Soute BA Vermeer C 16 May 1990 Comparison of the vitamins K1 K2 and K3 as cofactors for the hepatic vitamin K dependent carboxylase Biochimica et Biophysica Acta BBA General Subjects 1034 2 170 5 doi 10 1016 0304 4165 90 90072 5 PMID 2112953 Weber F Ruttimann A 2012 Vitamin K Ullmann s Encyclopedia Of Industrial Chemistry Weinheim Wiley VCH doi 10 1002 14356007 o27 o08 S2CID 86263542 de Souza AS Ribeiro RCB Costa DCS Pauli FP Pinho DR de Moraes MG da Silva FC Forezi LDSM Ferreira VF 2022 Menadione a platform and a target to valuable compounds synthesis Beilstein Journal of Organic Chemistry 18 381 419 doi 10 3762 bjoc 18 43 PMC 9039524 PMID 35529893 Menadione Sigma Aldrich Retrieved 2 February 2023 Vitamin K Substances and Animal Feed FDA 2 April 2021 EFSA Panel on Additives and Products or Substances used in Animal Feed FEEDAP January 2014 Scientific Opinion on the safety and efficacy of vitamin K3 menadione sodium bisulphite and menadione nicotinamide bisulphite as a feed additive for all animal species EFSA Journal 12 1 3532 doi 10 2903 j efsa 2014 3532 Menadione B02BA02 WHOCC ATC DDD Index a b Hassan Ghada S 2013 Menadione Profiles of Drug Substances Excipients and Related Methodology Vol 38 pp 227 313 doi 10 1016 B978 0 12 407691 4 00006 X ISBN 9780124076914 PMID 23668406 S2CID 242264898 Chiou TJ Zhang J Ferrans VJ Tzeng WF 31 December 1997 Cardiac and renal toxicity of menadione in rat Toxicology 124 3 193 202 doi 10 1016 s0300 483x 97 00162 5 PMID 9482121 External links editMenadione in the Pesticide Properties DataBase PPDB Retrieved from https en wikipedia org w index php title Menadione amp oldid 1210401376, wikipedia, wiki, book, books, library,
