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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2006-03-08 12:54:47 UTC
Update Date2020-02-26 21:23:35 UTC
HMDB IDHMDB0001892
Secondary Accession Numbers
  • HMDB01892
Metabolite Identification
Common NameMenadione
DescriptionMenadione is a synthetic naphthoquinone without the isoprenoid side chain and biological activity, but can be converted to active vitamin K2, menaquinone, after alkylation in vivo. -- Pubchem; 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. 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 cases. Moreover, menadione supplements have been banned by the FDA because of their high toxicity. It is sometimes called vitamin K3, although derivatives of naphthoquinone without the sidechain in the 3-position cannot exert all the functions of the K vitamins. Menadione is a vitamin precursor of K2 which utilizes alkylation in the liver to yield menaquinones (MK-n, n=1-13; K2 vitamers), and hence, is better classified as a provitamin. -- Wikipedia .
Structure
Data?1582752215
Synonyms
ValueSource
2-Methyl-1,4-naphthalenedioneChEBI
2-Methyl-1,4-naphthochinonChEBI
2-Methyl-1,4-naphthoquinoneChEBI
Vitamin K3ChEBI
KappaxinKegg
2-Methyl-1,4-naftochinonHMDB
2-Methyl-1,4-naphthalendioneHMDB
2-Methyl-1,4-naphthodioneHMDB
2-MethylnaphthoquinoneHMDB
3-Methyl-1,4-naphthoquinoneHMDB
AquakayHMDB
AquinoneHMDB
HemodalHMDB
Juva-KHMDB
K-ThrombylHMDB
K-VitanHMDB
KaergonaHMDB
KanoneHMDB
KappaxanHMDB
KarconHMDB
KareonHMDB
Kativ-gHMDB
KayklotHMDB
KaykotHMDB
KaynoneHMDB
KayquinoneHMDB
KipcaHMDB
Kipca-oil solubleHMDB
KlottoneHMDB
KoaxinHMDB
KolklotHMDB
MenadionHMDB
MenaphtheneHMDB
MenaphthonHMDB
MenaphthoneHMDB
MenaphtoneHMDB
MenaquinoneHMDB
Menaquinone OHMDB
MitenonHMDB
MitenoneHMDB
MNQHMDB
PanosineHMDB
ProkayvitHMDB
SynkayHMDB
ThyloquinoneHMDB
Vitamin K0HMDB
Vitamin K2HMDB
Vitamin K3: 1,4-dihydro-1,4-dioxo-2-methylnaphthaleneHMDB
Bisulfite, menadioneHMDB
VicasolHMDB
Bisulfite, menadione sodiumHMDB
Menadione sodium bisulfiteHMDB
VikasolHMDB
Vitamin K 3HMDB
Menadione sodium bisulfite, trihydrateHMDB
Vitamin K3 sodium bisulfiteHMDB
Menadione bisulfiteHMDB
Sodium bisulfite, menadioneHMDB
Chemical FormulaC11H8O2
Average Molecular Weight172.18
Monoisotopic Molecular Weight172.0524295
IUPAC Name2-methyl-1,4-dihydronaphthalene-1,4-dione
Traditional Namemenadione
CAS Registry Number58-27-5
SMILES
CC1=CC(=O)C2=CC=CC=C2C1=O
InChI Identifier
InChI=1S/C11H8O2/c1-7-6-10(12)8-4-2-3-5-9(8)11(7)13/h2-6H,1H3
InChI KeyMJVAVZPDRWSRRC-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as naphthoquinones. Naphthoquinones are compounds containing a naphthohydroquinone moiety, which consists of a benzene ring linearly fused to a bezene-1,4-dione (quinone).
KingdomOrganic compounds
Super ClassBenzenoids
ClassNaphthalenes
Sub ClassNaphthoquinones
Direct ParentNaphthoquinones
Alternative Parents
Substituents
  • Naphthoquinone
  • Aryl ketone
  • Quinone
  • Ketone
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point107 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.16 mg/mL at 30 °CYALKOWSKY,SH & DANNENFELSER,RM (1992)
LogP2.20HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.5 g/LALOGPS
logP1.91ALOGPS
logP1.89ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)12.94ChemAxon
pKa (Strongest Basic)-7.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity50.54 m³·mol⁻¹ChemAxon
Polarizability17.64 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0gk9-3900000000-ad6c0e599173ba802f73Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0ufr-2910000000-bbd6cf78055e623046a6Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0ufr-2910000000-5db665917b8c152a80b2Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0g4i-6900000000-0c6c7737ff416205089cSpectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0gk9-3900000000-ad6c0e599173ba802f73Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0ufr-2910000000-bbd6cf78055e623046a6Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0ufr-2910000000-5db665917b8c152a80b2Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-006x-1900000000-3c2bf459bf04eae7701dSpectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-074j-1900000000-a62dd17c23ac6e7fa95dSpectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0aor-1900000000-ce35b89eaf766c9398e8Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-004i-9100000000-65a9c21d7aa7be21de3aSpectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-80) , Positivesplash10-0g4i-6900000000-0c6c7737ff416205089cSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00di-1900000000-b489978f8a44b156f0f3Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-1900000000-b489978f8a44b156f0f3Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0900000000-ea17be197704c13eba82Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-2900000000-2d0b65ea01fe9dd6b4feSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-7900000000-509fb00927321d93a529Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0900000000-252f2831b39763f805b4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-0900000000-cea08e3f258cdd275a55Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00dr-6900000000-b84149529316a1f0987fSpectrum
MSMass Spectrum (Electron Ionization)splash10-0gk9-5900000000-48fb5ac08ce624a689ccSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableSpectrum
Biological Properties
Cellular LocationsNot Available
Biospecimen Locations
  • Blood
  • Urine
Tissue Locations
  • Fibroblasts
  • Kidney
  • Liver
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot Available
Normal
      Not Available
details
UrineDetected and Quantified0.00108 (0.0003-0.025) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.000411(0.0001-0.0011) umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00170
Phenol Explorer Compound IDNot Available
FooDB IDFDB000953
KNApSAcK IDNot Available
Chemspider ID3915
KEGG Compound IDC05377
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkMenadione
METLIN ID3910
PubChem Compound4055
PDB IDNot Available
ChEBI ID28869
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceMinami, Ryohei; Nishizaki, Tadao; Kumagai, Yoshitoshi. Menadione. Jpn. Kokai Tokkyo Koho (1986), 4 pp.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Robertson DG, Bailey DL, Martin RA: Species differences in response to photohemolytic agents. Photochem Photobiol. 1991 Apr;53(4):455-61. [PubMed:1857739 ]
  2. Chladek J, Martinkova J, Sispera L: An in vitro study on methotrexate hydroxylation in rat and human liver. Physiol Res. 1997;46(5):371-9. [PubMed:9728483 ]
  3. Habu D, Shiomi S, Tamori A, Takeda T, Tanaka T, Kubo S, Nishiguchi S: Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA. 2004 Jul 21;292(3):358-61. [PubMed:15265851 ]
  4. Lasalvia-Prisco E, Cucchi S, Vazquez J, Lasalvia-Galante E, Golomar W, Gordon W: Serum markers variation consistent with autoschizis induced by ascorbic acid-menadione in patients with prostate cancer. Med Oncol. 2003;20(1):45-52. [PubMed:12665684 ]
  5. Harrington DJ, Soper R, Edwards C, Savidge GF, Hodges SJ, Shearer MJ: Determination of the urinary aglycone metabolites of vitamin K by HPLC with redox-mode electrochemical detection. J Lipid Res. 2005 May;46(5):1053-60. Epub 2005 Feb 1. [PubMed:15722567 ]
  6. Kwasnicka-Crawford DA, Vincent SR: Role of a novel dual flavin reductase (NR1) and an associated histidine triad protein (DCS-1) in menadione-induced cytotoxicity. Biochem Biophys Res Commun. 2005 Oct 21;336(2):565-71. [PubMed:16140270 ]
  7. Snider BJ, Moss JL, Revilla FJ, Lee CS, Wheeler VC, Macdonald ME, Choi DW: Neocortical neurons cultured from mice with expanded CAG repeats in the huntingtin gene: unaltered vulnerability to excitotoxins and other insults. Neuroscience. 2003;120(3):617-25. [PubMed:12895502 ]
  8. Usui Y, Tanimura H, Nishimura N, Kobayashi N, Okanoue T, Ozawa K: Vitamin K concentrations in the plasma and liver of surgical patients. Am J Clin Nutr. 1990 May;51(5):846-52. [PubMed:2333843 ]
  9. Ono M, Ohta H, Ohhira M, Sekiya C, Namiki M: Measurement of immunoreactive prothrombin, des-gamma-carboxy prothrombin, and vitamin K in human liver tissues: overproduction of immunoreactive prothrombin in hepatocellular carcinoma. Am J Gastroenterol. 1990 Sep;85(9):1149-54. [PubMed:1697141 ]
  10. Suzuki S, Iwata G, Sutor AH: Vitamin K deficiency during the perinatal and infantile period. Semin Thromb Hemost. 2001;27(2):93-8. [PubMed:11372776 ]
  11. Wermuth B, Platts KL, Seidel A, Oesch F: Carbonyl reductase provides the enzymatic basis of quinone detoxication in man. Biochem Pharmacol. 1986 Apr 15;35(8):1277-82. [PubMed:3083821 ]
  12. Price RJ, Mistry H, Wield PT, Renwick AB, Beamand JA, Lake BG: Comparison of the toxicity of allyl alcohol, coumarin and menadione in precision-cut rat, guinea-pig, cynomolgus monkey and human liver slices. Arch Toxicol. 1996;71(1-2):107-11. [PubMed:9010592 ]
  13. Thijssen HH, Drittij-Reijnders MJ: Vitamin K status in human tissues: tissue-specific accumulation of phylloquinone and menaquinone-4. Br J Nutr. 1996 Jan;75(1):121-7. [PubMed:8785182 ]
  14. Iioka H, Moriyama IS, Morimoto K, Akada S, Hisanaga H, Ishihara Y, Ichijo M: Pharmacokinetics of vitamin K in mothers and children in the perinatal period: transplacental transport of vitamin K2 (MK-4). Asia Oceania J Obstet Gynaecol. 1991 Mar;17(1):97-100. [PubMed:2064595 ]
  15. Strunnikova N, Hilmer S, Flippin J, Robinson M, Hoffman E, Csaky KG: Differences in gene expression profiles in dermal fibroblasts from control and patients with age-related macular degeneration elicited by oxidative injury. Free Radic Biol Med. 2005 Sep 15;39(6):781-96. [PubMed:16109308 ]

Only showing the first 10 proteins. There are 23 proteins in total.

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Reduces all-trans-retinal and 9-cis retinal. Can also catalyze the oxidation of all-trans-retinol with NADP as co-factor, but with much lower efficiency. Reduces alkyl phenyl ketones and alpha-dicarbonyl compounds with aromatic rings, such as pyrimidine-4-aldehyde, 3-benzoylpyridine, 4-benzoylpyridine, menadione and 4-hexanoylpyridine. Has no activity towards aliphatic aldehydes and ketones (By similarity).
Gene Name:
DHRS4
Uniprot ID:
Q9BTZ2
Molecular weight:
29536.885
General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
AOX1
Uniprot ID:
Q06278
Molecular weight:
147916.735
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in electron carrier activity
Specific function:
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.
Gene Name:
NQO2
Uniprot ID:
P16083
Molecular weight:
25918.4
References
  1. Long DJ 2nd, Iskander K, Gaikwad A, Arin M, Roop DR, Knox R, Barrios R, Jaiswal AK: Disruption of dihydronicotinamide riboside:quinone oxidoreductase 2 (NQO2) leads to myeloid hyperplasia of bone marrow and decreased sensitivity to menadione toxicity. J Biol Chem. 2002 Nov 29;277(48):46131-9. Epub 2002 Sep 25. [PubMed:12351651 ]
  2. Kwiek JJ, Haystead TA, Rudolph J: Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines. Biochemistry. 2004 Apr 20;43(15):4538-47. [PubMed:15078100 ]
  3. Foster CE, Bianchet MA, Talalay P, Zhao Q, Amzel LM: Crystal structure of human quinone reductase type 2, a metalloflavoprotein. Biochemistry. 1999 Aug 3;38(31):9881-6. [PubMed:10433694 ]
  4. Celli CM, Tran N, Knox R, Jaiswal AK: NRH:quinone oxidoreductase 2 (NQO2) catalyzes metabolic activation of quinones and anti-tumor drugs. Biochem Pharmacol. 2006 Jul 28;72(3):366-76. Epub 2006 May 4. [PubMed:16765324 ]
  5. Boutin JA, Chatelain-Egger F, Vella F, Delagrange P, Ferry G: Quinone reductase 2 substrate specificity and inhibition pharmacology. Chem Biol Interact. 2005 Feb 10;151(3):213-28. [PubMed:15733542 ]
General function:
Involved in oxidoreductase activity
Specific function:
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
Gene Name:
XDH
Uniprot ID:
P47989
Molecular weight:
146422.99
References
  1. Yee SB, Pritsos CA: Comparison of oxygen radical generation from the reductive activation of doxorubicin, streptonigrin, and menadione by xanthine oxidase and xanthine dehydrogenase. Arch Biochem Biophys. 1997 Nov 15;347(2):235-41. [PubMed:9367530 ]
General function:
Involved in oxidoreductase activity
Specific function:
This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
Gene Name:
POR
Uniprot ID:
P16435
Molecular weight:
77047.575
General function:
Involved in methylenetetrahydrofolate reductase (NADPH) activity
Specific function:
Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.
Gene Name:
MTHFR
Uniprot ID:
P42898
Molecular weight:
74595.895
References
  1. Vanoni MA, Ballou DP, Matthews RG: Methylenetetrahydrofolate reductase. Steady state and rapid reaction studies on the NADPH-methylenetetrahydrofolate, NADPH-menadione, and methyltetrahydrofolate-menadione oxidoreductase activities of the enzyme. J Biol Chem. 1983 Oct 10;258(19):11510-4. [PubMed:6352699 ]
  2. Clark JE, Ljungdahl LG: Purification and properties of 5,10-methylenetetrahydrofolate reductase, an iron-sulfur flavoprotein from Clostridium formicoaceticum. J Biol Chem. 1984 Sep 10;259(17):10845-9. [PubMed:6381490 ]
General function:
Involved in receptor signaling protein serine/threonine kinase activity
Specific function:
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin. May be involved for left-right pattern formation during embryogenesis
Gene Name:
ACVR1
Uniprot ID:
Q04771
Molecular weight:
57152.4
General function:
Involved in monooxygenase activity
Specific function:
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular weight:
56848.42
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular weight:
58164.815
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Only showing the first 10 proteins. There are 23 proteins in total.