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関: See also Vitamin K

関: See also Vitamin K

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/02/06 09:18:16」(JST)

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Menadione is a synthetic chemical compound sometimes used as a nutritional supplement because of its vitamin K activity. It is an analog of 1,4-naphthoquinone with a methyl group in the 2-position.^[2]

Terminology

It is sometimes called vitamin K₃,^[3] although derivatives of naphthoquinone without the side chain in the 3-position cannot exert all the functions of the K vitamins. Menadione is a vitamin precursor of K₂ which utilizes alkylation to yield menaquinones (MK-n, n=1-13; K₂ vitamers), and hence, is better classified as a provitamin.

It is also known as "menaphthone".^[4]

Uses

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. Large doses of menadione have been reported to cause adverse outcomes including hemolytic anemia due to G6PD deficiency, neonatal brain or liver damage, or neonatal death in some rare cases. In the United States, menadione supplements are banned by the U.S. Food and Drug Administration (FDA) because of their potential toxicity in human use.

Low dose menadione is still 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.

It is used in the treatment of Hypoprothrombinemia outside of the united states

Experimental research

Menadione has been used experimentally as a chemotherapic agent for cancer since 1947.^{[citation needed]} More recently, menadione in combination with vitamin C is being studied as a potential treatment for prostate cancer.^[5]^[6]

A menadione topical lotion was recently developed to reduce epidermal growth factor receptor inhibitor related side effects, by the prevention of skin toxicities that result from inhibition of protein kinases by drugs such as erlotinib (Tarceva) and cetuximab (Erbitux).^[7]^[8]

References

^ The Merck Index, 11th Edition, 5714
^ Castro FA, Mariani D, Panek AD, Eleutherio EC, Pereira MD (2008). Fox, Debbie. ed. "Cytotoxicity Mechanism of Two Naphthoquinones (Menadione and Plumbagin) in Saccharomyces cerevisiae". PLoS ONE 3 (12): e3999. doi:10.1371/journal.pone.0003999. PMC 2600608. PMID 19098979. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003999.
^ Scott GK, Atsriku C, Kaminker P, et al (September 2005). "Vitamin K3 (menadione)-induced oncosis associated with keratin 8 phosphorylation and histone H3 arylation". Mol. Pharmacol. 68 (3): 606–15. doi:10.1124/mol.105.013474. PMID 15939799. http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15939799.
^ "Vitamin K". http://www.umm.edu/altmed/articles/vitamin-k-000343.htm. Retrieved 2009-03-18.
^ James M. Jamison, Jacques Gilloteaux, Henryk S. Taper and Jack L. Summers (2001). "Evaluation of the In Vitro and In Vivo Antitumor Activities of Vitamin C and K-3 Combinations against Human Prostate Cancer". J. Nutr. 131 (1): 158S–160S. PMID 11208954. http://jn.nutrition.org/cgi/reprint/131/1/158S.pdf.
^ Tareen B, Summers JL, Jamison JM, Neal DR, McGuire K, Gerson L, Diokno A (2008). "A 12 Week, Open Label, Phase I/IIa Study Using Apatone® for the Treatment of Prostate Cancer Patients Who Have Failed Standard Therapy". Int J Med Sci 5 (2): 62–67. PMC 2288789. PMID 18392145. http://www.medsci.org/v05p0062.htm.
^ R. Perez-Soler, Y. Ling, Y. Zou, S.R. Deitcher (2008). "Local Rescue of Skin Toxicities Secondary to Kinase Inhibitor (KI) Therapy with Topical Menadione". Annals of Oncology. http://annonc.oxfordjournals.org/content/19/suppl_5/v164.full.pdf.
^ Tianhong Li and Roman Perez-Soler (2009). "Skin toxicities associated with epidermal growth factor receptor inhibitors". Targeted Oncology 4 (2): 107–119. doi:10.1007/s11523-009-0114-0. PMID 19452131. http://www.springerlink.com/content/x6712t382565u144/.

UpToDate Contents

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1. ビタミンKの概要 overview of vitamin k
2. ミトコンドリア細胞症における腎病変 renal involvement in the mitochondrial cytopathies
3. ミトコンドリアミオパシー：治療 mitochondrial myopathies treatment

English Journal

Molecular insights into human monoamine oxidase (MAO) inhibition by 1,4-naphthoquinone: Evidences for menadione (vitamin K3) acting as a competitive and reversible inhibitor of MAO.

Coelho Cerqueira E, Netz PA, Diniz C, Petry do Canto V, Follmer C.SourceDepartment of Physical Chemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro 21941-909, Brazil.
Bioorganic & medicinal chemistry.Bioorg Med Chem.2011 Dec 15;19(24):7416-24. Epub 2011 Oct 20.
Monoamine oxidase (MAO) catalyzes the oxidative deamination of biogenic and exogenous amines and its inhibitors have therapeutic value for several conditions including affective disorders, stroke, neurodegenerative diseases and aging. The discovery of 2,3,6-trimethyl-1,4-naphthoquinone (TMN) as a no
PMID 22071524

Intracellular ATP levels determine cell death fate of cancer cells exposed to both standard and redox chemotherapeutic agents.

Verrax J, Dejeans N, Sid B, Glorieux C, Calderon PB.SourceToxicology and Cancer Biology Research Group (TOXCAN), Louvain Drug Research Institute, Université catholique de Louvain, Belgium.
Biochemical pharmacology.Biochem Pharmacol.2011 Dec 1;82(11):1540-8. Epub 2011 Aug 9.
Cancer cells generally exhibit high levels of reactive oxygen species (ROS) that stimulate cell proliferation and promote genetic instability. Since this biochemical difference between normal and cancer cells represents a specific vulnerability that can be selectively targeted for cancer therapy, va
PMID 21843513

Japanese Journal

メダカに対するメナジオン(ビタミンK3)およびその光派性物質の影響評価

山口明美,高良真也,有薗幸司 [他]
環境毒性学会誌 14(1), 141-148, 2011-06
NAID 40018958651

Preparations of Anthraquinone and Naphthoquinone Derivatives and Their Cytotoxic Effects

Cui Xing-Ri,Saito Ryota,Kubo Takatsugu,Kon Daijiro,Hirano Yuich,Saito Setsuo
CHEMICAL & PHARMACEUTICAL BULLETIN 59(3), 302-314, 2011
… Furthermore, derivatives of menadione substituted at position 11 (type A naphthoquinone derivatives) or methylmenadione substituted at position 7 (type B naphthoquinone derivatives) modified with nucleic acid bases, amines and thiocyano, selenocyano or thioacetyl groups were synthesized. …
NAID 130000648937

Related Pictures

★リンクテーブル★

リンク元	「ビタミンK」「メナジオン」
拡張検索	「phytomenadione」

「ビタミンK」

Menadione
	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
CAS number	58-27-5
PubChem	4055
ChemSpider	3915
UNII	723JX6CXY5
DrugBank	DB00170
KEGG	D02335
ChEBI	CHEBI:28869
ChEMBL	CHEMBL590
ATC code	B02BA02
Jmol-3D images	Image 1
	SMILES O=C\2c1c(cccc1)C(=O)/C(=C/2)C ;
	InChI InChI=1S/C11H8O2/c1-7-6-10(12)8-4-2-3-5-9(8)11(7)13/h2-6H,1H3 ; Key: MJVAVZPDRWSRRC-UHFFFAOYSA-N InChI=1/C11H8O2/c1-7-6-10(12)8-4-2-3-5-9(8)11(7)13/h2-6H,1H3; Key: MJVAVZPDRWSRRC-UHFFFAOYAY ;
Properties
Molecular formula	C11H8O2
Molar mass	172.18 g mol−1
Appearance	Bright yellow crystals
Density	1.225g/cm3
Melting point	105–107 °C
Boiling point	304.5 °C @ 760mmHg
Solubility in water	Insoluble
Hazards
Flash point	113.8 °C
LD50	0.5 g/kg (oral, mouse)
	(verify) (what is: /?); Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
	Infobox references

　　[★]

英: vitamin K, VK
関: ビタミン、(薬剤として存在)フィトナジオン(=ビタミンK1)

図：SPC.360
脂溶性ビタミン
止血薬

種類

ビタミンK₁：phytonadione
ビタミンK₂：menadione
ビタミンK₃：人工合成

生理作用

ビタミンKはγ-glutamyl carboxylase(多分、Ca2+を補酵素として用いる酵素の総称で、γ-carboxyglutamate residueを有する)に必要である。
血液凝固に必要な因子の肝臓における生合成を促進 (SPC.360)

第II因子(プロトロンビン)、第VII因子、第IX因子、第X因子の産生を促進 (SPC.292改)

促進というより、凝固因子のグルタミン酸をγ-カルボキシグルタミン酸(Gla)に変換しないとセリンプロテアーゼとしての酵素活性を発揮できないということ？

プロテインC、プロテインSもビタミンK依存的である。

代謝系を介するので、作用の発現は遅い

血液凝固因子やオステオカルシンの前駆体のプロセッシングに必須であり、補酵素として働く。

bone Gla proteinやmatrix Gla proteinといった骨の石灰化に関与する蛋白質の補酵素として働いており、またビタミンK1(phylloquinone)やビタミンK2は骨粗鬆症の治療薬として臨床試験が進められている(参考1)。

体内産生

腸内細菌によって合成

低栄養or肝障害の存在するとき腸内細菌を死滅させるような広域抗生剤の使用　→　ビタミンK欠乏症

吸収

胆汁により吸収が媒介される

閉塞性黄疸　→　ビタミンK欠乏症

適応

クマリン誘導体による低プロトロンビン血症による出血

==禁忌

臨床関連

ビタミンK欠乏症

特発性乳児ビタミンK欠乏性出血症(乳児ビタミンK欠乏性出血症)

新生児メレナ

閉塞性黄疸、膵臓疾患、小腸疾患(例えばクローン病)、下痢、抗菌薬の長期連用

ビタミンKに依存している血液凝固因子の血中半減期は、以下の通りなので、PTでビタミンK欠乏症のスクリーニングが行われるらしい

半減期(hr)：F II(50-80) > F X(25-60) > F IX](24) >F VII(6)

参考

1. [charged] ビタミンKの概要 - uptodate [1]

「メナジオン」

　　[★]

英: menadione
関: ビタミンK3

「phytomenadione」

　　[★]

フィトメナジオン

関: phylloquinone、phytonadione、vitamin K1

[1] The Merck Index, 11th Edition, 5714

[pmid19098979-2] Castro FA, Mariani D, Panek AD, Eleutherio EC, Pereira MD (2008). Fox, Debbie. ed. "Cytotoxicity Mechanism of Two Naphthoquinones (Menadione and Plumbagin) in Saccharomyces cerevisiae". PLoS ONE 3 (12): e3999. doi:10.1371/journal.pone.0003999. PMC 2600608. PMID 19098979. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003999.

[pmid15939799-3] Scott GK, Atsriku C, Kaminker P, et al (September 2005). "Vitamin K3 (menadione)-induced oncosis associated with keratin 8 phosphorylation and histone H3 arylation". Mol. Pharmacol. 68 (3): 606–15. doi:10.1124/mol.105.013474. PMID 15939799. http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15939799.

[urlVitamin_K-4] "Vitamin K". http://www.umm.edu/altmed/articles/vitamin-k-000343.htm. Retrieved 2009-03-18.

[5] James M. Jamison, Jacques Gilloteaux, Henryk S. Taper and Jack L. Summers (2001). "Evaluation of the In Vitro and In Vivo Antitumor Activities of Vitamin C and K-3 Combinations against Human Prostate Cancer". J. Nutr. 131 (1): 158S–160S. PMID 11208954. http://jn.nutrition.org/cgi/reprint/131/1/158S.pdf.

[6] Tareen B, Summers JL, Jamison JM, Neal DR, McGuire K, Gerson L, Diokno A (2008). "A 12 Week, Open Label, Phase I/IIa Study Using Apatone® for the Treatment of Prostate Cancer Patients Who Have Failed Standard Therapy". Int J Med Sci 5 (2): 62–67. PMC 2288789. PMID 18392145. http://www.medsci.org/v05p0062.htm.

[7] R. Perez-Soler, Y. Ling, Y. Zou, S.R. Deitcher (2008). "Local Rescue of Skin Toxicities Secondary to Kinase Inhibitor (KI) Therapy with Topical Menadione". Annals of Oncology. http://annonc.oxfordjournals.org/content/19/suppl_5/v164.full.pdf.

[8] Tianhong Li and Roman Perez-Soler (2009). "Skin toxicities associated with epidermal growth factor receptor inhibitors". Targeted Oncology 4 (2): 107–119. doi:10.1007/s11523-009-0114-0. PMID 19452131. http://www.springerlink.com/content/x6712t382565u144/.

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menadione