Jump to content

Menadione

From Wikipedia, the free encyclopedia
Not to confuse withmenaquinone-3,aka MK-3, a version ofvitamin K2series having 3 isoprene groups
Menadione[1]
Skeltal formula
Ball-and-stick model
Names
Preferred IUPAC name
2-Methylnaphthalene-1,4-dione
Other names
Menaphthone; Vitamin K3;β-Methyl-1,4-naphthoquinone; 2-Methyl-1,4-naphthodione; 2-Methyl-1,4-naphthoquinone
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.338Edit this at Wikidata
KEGG
UNII
  • InChI=1S/C11H8O2/c1-7-6-10(12)8-4-2-3-5-9(8)11(7)13/h2-6H,1H3checkY
    Key: MJVAVZPDRWSRRC-UHFFFAOYSA-NcheckY
  • InChI=1/C11H8O2/c1-7-6-10(12)8-4-2-3-5-9(8)11(7)13/h2-6H,1H3
    Key: MJVAVZPDRWSRRC-UHFFFAOYAY
  • O=C\2c1c(cccc1)C(=O)/C(=C/2)C
Properties
C11H8O2
Molar mass 172.183g·mol−1
Appearance Bright yellow crystals
Density 1.225g/cm3
Melting point 105 to 107 °C (221 to 225 °F; 378 to 380 K)
Insoluble
Pharmacology
B02BA02(WHO)
  • Contraindicated (India)[2]
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  • Generally Rx or withdrawn for human use; approved in animal feed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 doseor concentration (LD, LC):
0.5 g/kg (oral, mouse)
Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa).

Menadioneis a natural[3]organic compoundwith the formula C6H4(CO)2C2H(CH3). It is ananalogof1,4-naphthoquinonewith amethyl groupin the 2-position.[4]It is sometimes calledvitamin K3.Use is allowed as anutritional supplementinanimal feedbecause of itsvitamin Kactivity.

Biochemistry[edit]

Menadione is converted tovitamin K2(specifically,MK-4) by theprenyltransferaseaction ofvertebrateUBIAD1.[3]This reaction requires the hydroquinone (reduced) form of K3,menadiol,produced byNQO1.[5]

Menadione is also a circulating form of vitamin K, produced in small amounts (1–5%) after intestinal absorption of K1and K2.This circulation explains the uneven tissue distribution of MK-4, especially since menadione can penetrate theblood–brain barrier.The cleavage enzyme is yet to be identified. As K3is known to be toxic in large amounts, researchers speculate that the cleavage process is closely regulated.[5]

Terminology[edit]

The compound is variously known as vitamin K3[6]andprovitaminK3.[7]Proponents of the latter name generally argue that the compound is not a realvitamindue 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 forGGCXin vitro)[8]of the K vitamins.

Uses[edit]

The menadione core is apparent in the structure ofvitamin K.

It is an intermediate in the chemical synthesis of vitamin K by first reduction to thediolmenadiol,which is susceptible to coupling to thephytol.[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 generatereactive oxygen speciesto perform flow cytometry analysis on. It can also be used in microbiological evaluation to, for example, detectfastidiousmicroorganisms.[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, theEuropean Food Safety Authorityfound 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 ofvitamin 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 ofhypoprothrombinemiaoutside of the United States.[2]

Toxicology[edit]

Menadione is not believed to be carcinogenic.[15]K3 can cause generation of reactive oxygen species (ROS) byredox cyclingand 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]

  1. ^The Merck Index,11th Edition,5714
  2. ^abc"Menadione drug information".DrugsUpdate India.
  3. ^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.ISSN1083-351X.PMC3829156.PMID24085302.
  4. ^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.PMID19098979.
  5. ^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.ISSN0022-2275.PMC3934721.PMID24489112.
  6. ^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.PMID15939799.S2CID19076885.
  7. ^"Vitamin K".Linus Pauling Institute.2014-04-22.Retrieved2021-01-28.
  8. ^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.PMID2112953.
  9. ^Weber F, Rüttimann A (2012). "Vitamin K".Ullmann's Encyclopedia Of Industrial Chemistry.Weinheim: Wiley-VCH.doi:10.1002/14356007.o27_o08.S2CID86263542.
  10. ^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.PMID35529893.
  11. ^"Menadione".Sigma-Aldrich.Retrieved2 February2023.
  12. ^"Vitamin K Substances and Animal Feed".FDA.2 April 2021.
  13. ^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.
  14. ^"Menadione (B02BA02)".WHOCC - ATC/DDD Index.
  15. ^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.PMID23668406.S2CID242264898.
  16. ^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.PMID9482121.

External links[edit]

  • Menadionein the Pesticide Properties DataBase (PPDB)
Retrieved from "https://en.wikipedia.org/w/index.php?title=Menadione&oldid=1210401376"