Manganese (T3D0117)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (10)XML
Targets (10)
Record Information
Version2.0
Creation Date2009-03-06 18:58:06 UTC
Update Date2014-12-24 20:21:08 UTC
Accession NumberT3D0117
Identification
Common NameManganese
ClassSmall Molecule
DescriptionManganese is an essential trace nutrient in all forms of life. Physiologically, it. exists as an ion in the body. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver.
Compound Type
  • Cosmetic Toxin
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Inorganic Compound
  • Manganese Compound
  • Metabolite
  • Metal
  • Natural Compound
  • Pollutant
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Magnanese(2+)
Manganese ion
Manganese(2+) ion
Manganese(II)
Manganese(II) cation
Manganese(II) ion
Metallic manganese
Mn(2+)
Mn2+
Chemical FormulaMn
Average Molecular Mass54.937 g/mol
Monoisotopic Mass54.937 g/mol
CAS Registry Number7439-96-5
IUPAC Namemanganese(2+) ion
Traditional Namemanganese(2+) ion
SMILES[Mn++]
InChI IdentifierInChI=1S/Mn/q+2
InChI KeyInChIKey=WAEMQWOKJMHJLA-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as homogeneous transition metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a transition metal atom.
KingdomInorganic compounds
Super ClassHomogeneous metal compounds
ClassHomogeneous transition metal compounds
Sub ClassNot Available
Direct ParentHomogeneous transition metal compounds
Alternative ParentsNot Available
Substituents
  • Homogeneous transition metal
Molecular FrameworkNot Available
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Basal Ganglia
  • Brain
  • Central Nervous System
  • Hair
  • Liver
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point1244°C
Boiling Point2095°C (3803°F)
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
logP-0.16ChemAxon
pKa (Strongest Acidic)3.09ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity0 m³·mol⁻¹ChemAxon
Polarizability1.78 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-9000000000-6f3891a406ae3fe4f8832015-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9000000000-6f3891a406ae3fe4f8832015-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000000000-6f3891a406ae3fe4f8832015-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-9000000000-c3110d268939143a5f802015-09-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-9000000000-c3110d268939143a5f802015-09-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0udi-9000000000-c3110d268939143a5f802015-09-15View Spectrum
Toxicity Profile
Route of ExposureOral (23) ; inhalation (23)
Mechanism of ToxicityManganese is a cellular toxicant that can impair transport systems, enzyme activities, and receptor functions. It primarily targets the central nervous system, particularily the globus pallidus of the basal ganglia. It is believed that the manganese ion, Mn(II), enhances the autoxidation or turnover of various intracellular catecholamines, leading to increased production of free radicals, reactive oxygen species, and other cytotoxic metabolites, along with a depletion of cellular antioxidant defense mechanisms, leading to oxidative damage and selective destruction of dopaminergic neurons. In addition to dopamine, manganese is thought to interact with other neurotransmitters, such as GABA and glutamate. Manganese overwhelms the manganese superoxide dismutase and produce oxidative damage. The neurotoxicity of Mn(II) has also been linked to its ability to substitute for Ca(II) under physiological conditions. It can enter mitochondria via the calcium uniporter and inhibit mitochondrial oxidative phosphorylation. It may also inhibit the efflux of Ca(II), which can result in a loss of mitochondrial membrane integrity. Mn(II) has been shown to inhibit mitochondrial aconitase activity to a significant level, altering amino acid metabolism and cellular iron homeostasis. (23)
MetabolismManganese is mainly absorbed via ingestion, but can also be inhaled. It binds to alpha-2-macroglobulin, albumin, or transferrin in the plasma and is distributed to the brain and all other mammalian tissues, though it tends to accumulate more in the liver, pancreas, and kidney. Manganese exists in a number of oxidation states and is believed to undergo changes in oxidation state within the body. Manganese oxidation state can influence tissue toxicokinetic behavior, and possibly toxicity. Manganese is excreted primarily in the faeces. (23)
Toxicity ValuesLD50: 9 g/kg (Oral, Rat) (21)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesManganese is used principally in steel production to improve hardness, stiffness, and strength. It may also be used as an additive in gasoline to improve the octane rating of the gas. Manganese ions have various colors and are used industrially as pigments. (23, 24)
Minimum Risk LevelChronic Inhalation: 0.0003 mg/m3 (22)
Health EffectsManganese mainly affects the nervous system and may cause behavioral changes and other nervous system effects, which include movements that may become slow and clumsy. This combination of symptoms when sufficiently severe is referred to as “manganism”. High levels of manganese may also cause damage to the reproductive system. (23)
SymptomsManganese mainly affects the nervous system and may cause behavioral changes and other nervous system effects, which include movements that may become slow and clumsy. This combination of symptoms when sufficiently severe is referred to as “manganism”. (23)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB01333
PubChem Compound ID27854
ChEMBL IDNot Available
ChemSpider ID25916
KEGG IDC19610
UniProt IDNot Available
OMIM ID153550 , 173470
ChEBI ID29035
BioCyc IDMN%2b3
CTD IDD008345
Stitch IDManganese
PDB IDMN
ACToR ID6475
Wikipedia LinkManganese
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Ikeda S, Sera Y, Yoshida M, Ohshiro H, Uchino S, Oka Y, Lee KJ, Kotera A: Manganese deposits in patients with biliary atresia after hepatic porto-enterostomy. J Pediatr Surg. 2000 Mar;35(3):450-3. [10726687 ]
  2. Greger JL: Nutrition versus toxicology of manganese in humans: evaluation of potential biomarkers. Neurotoxicology. 1999 Apr-Jun;20(2-3):205-12. [10385884 ]
  3. Lander F, Kristiansen J, Lauritsen JM: Manganese exposure in foundry furnacemen and scrap recycling workers. Int Arch Occup Environ Health. 1999 Nov;72(8):546-50. [10592008 ]
  4. Mizoguchi N, Nishimura Y, Ono H, Sakura N: Manganese elevations in blood of children with congenital portosystemic shunts. Eur J Pediatr. 2001 Apr;160(4):247-50. [11317649 ]
  5. Woolf A, Wright R, Amarasiriwardena C, Bellinger D: A child with chronic manganese exposure from drinking water. Environ Health Perspect. 2002 Jun;110(6):613-6. [12055054 ]
  6. Ikeda S, Yamaguchi Y, Sera Y, Ohshiro H, Uchino S, Yamashita Y, Ogawa M: Manganese deposition in the globus pallidus in patients with biliary atresia. Transplantation. 2000 Jun 15;69(11):2339-43. [10868637 ]
  7. Wardle CA, Forbes A, Roberts NB, Jawhari AV, Shenkin A: Hypermanganesemia in long-term intravenous nutrition and chronic liver disease. JPEN J Parenter Enteral Nutr. 1999 Nov-Dec;23(6):350-5. [10574484 ]
  8. Mergler D, Baldwin M, Belanger S, Larribe F, Beuter A, Bowler R, Panisset M, Edwards R, de Geoffroy A, Sassine MP, Hudnell K: Manganese neurotoxicity, a continuum of dysfunction: results from a community based study. Neurotoxicology. 1999 Apr-Jun;20(2-3):327-42. [10385894 ]
  9. Butterworth RF: Hepatic encephalopathy. Alcohol Res Health. 2003;27(3):240-6. [15535452 ]
  10. Herynek V, Babis M, Trunecka P, Filip K, Vymazal J, Dezortova M, Hajek M: Chronic liver disease: relaxometry in the brain after liver transplantation. MAGMA. 2001 Mar;12(1):10-5. [11255087 ]
  11. Miranda M, Caballero L: [Chronic hepatic encephalopathy: the role of high serum manganese levels and its relation with basal ganglia lesions in nuclear magnetic resonance of the brain. Clinical case]. Rev Med Chil. 2001 Sep;129(9):1051-5. [11725469 ]
  12. Barceloux DG: Manganese. J Toxicol Clin Toxicol. 1999;37(2):293-307. [10382563 ]
  13. Bader M, Dietz MC, Ihrig A, Triebig G: Biomonitoring of manganese in blood, urine and axillary hair following low-dose exposure during the manufacture of dry cell batteries. Int Arch Occup Environ Health. 1999 Nov;72(8):521-7. [10592004 ]
  14. Kao HJ, Chen WH, Liu JS: Rapid progression of parkinsonism associated with an increase of blood manganese. Kaohsiung J Med Sci. 1999 May;15(5):297-301. [10375873 ]
  15. Melo TM, Larsen C, White LR, Aasly J, Sjobakk TE, Flaten TP, Sonnewald U, Syversen T: Manganese, copper, and zinc in cerebrospinal fluid from patients with multiple sclerosis. Biol Trace Elem Res. 2003 Summer;93(1-3):1-8. [12835484 ]
  16. Lees-Haley PR, Rohling ML, Langhinrichsen-Rohling J: A meta-analysis of the neuropsychological effects of occupational exposure to manganese. Clin Neuropsychol. 2006 Feb;20(1):90-107. [16393922 ]
  17. Sadek AH, Rauch R, Schulz PE: Parkinsonism due to manganism in a welder. Int J Toxicol. 2003 Sep-Oct;22(5):393-401. [14555414 ]
  18. Wang X, Li GJ, Zheng W: Upregulation of DMT1 expression in choroidal epithelia of the blood-CSF barrier following manganese exposure in vitro. Brain Res. 2006 Jun 30;1097(1):1-10. Epub 2006 May 26. [16729984 ]
  19. Takeda A: Manganese action in brain function. Brain Res Brain Res Rev. 2003 Jan;41(1):79-87. [12505649 ]
  20. Baldwin M, Mergler D, Larribe F, Belanger S, Tardif R, Bilodeau L, Hudnell K: Bioindicator and exposure data for a population based study of manganese. Neurotoxicology. 1999 Apr-Jun;20(2-3):343-53. [10385895 ]
  21. National Institute for Occupational Safety and Health (2002). RTECS: Registry of Toxic Effects of Chemical Substances.
  22. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  23. ATSDR - Agency for Toxic Substances and Disease Registry (2008). Toxicological profile for manganese. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  24. Wikipedia. Manganese. Last Updated 26 May 2009. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. Aconitate hydratase, mitochondrial
General Function:
Iron ion binding
Specific Function:
Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.
Gene Name:
ACO2
Uniprot ID:
Q99798
Molecular Weight:
85424.745 Da
References
  1. Crooks DR, Ghosh MC, Braun-Sommargren M, Rouault TA, Smith DR: Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells. J Neurosci Res. 2007 Jun;85(8):1797-809. [17469137 ]
Target Details
2. Arginase-1
General Function:
Manganese ion binding
Specific Function:
Not Available
Gene Name:
ARG1
Uniprot ID:
P05089
Molecular Weight:
34734.655 Da
References
  1. Zakharian TY, Di Costanzo L, Christianson DW: Synthesis of (2S)-2-amino-7,8-epoxyoctanoic acid and structure of its metal-bridging complex with human arginase I. Org Biomol Chem. 2008 Sep 21;6(18):3240-3. doi: 10.1039/b811797g. Epub 2008 Aug 6. [18802628 ]
Target Details
3. Cytoplasmic aconitate hydratase
General Function:
Rna binding
Specific Function:
Iron sensor. Binds a 4Fe-4S cluster and functions as aconitase when cellular iron levels are high. Functions as mRNA binding protein that regulates uptake, sequestration and utilization of iron when cellular iron levels are low. Binds to iron-responsive elements (IRES) in target mRNA species when iron levels are low. Binding of a 4Fe-4S cluster precludes RNA binding.Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.
Gene Name:
ACO1
Uniprot ID:
P21399
Molecular Weight:
98398.14 Da
References
  1. Crooks DR, Ghosh MC, Braun-Sommargren M, Rouault TA, Smith DR: Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells. J Neurosci Res. 2007 Jun;85(8):1797-809. [17469137 ]
Target Details
4. Iron-responsive element-binding protein 2
General Function:
Translation repressor activity
Specific Function:
RNA-binding protein that binds to iron-responsive elements (IRES), which are stem-loop structures found in the 5'-UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of transferrin receptor mRNA. Binding to the IRE element in ferritin results in the repression of its mRNA translation. Binding of the protein to the transferrin receptor mRNA inhibits the degradation of this otherwise rapidly degraded mRNA.
Gene Name:
IREB2
Uniprot ID:
P48200
Molecular Weight:
105043.65 Da
References
  1. Crooks DR, Ghosh MC, Braun-Sommargren M, Rouault TA, Smith DR: Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells. J Neurosci Res. 2007 Jun;85(8):1797-809. [17469137 ]
Target Details
5. Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial
General Function:
Nad binding
Specific Function:
Not Available
Gene Name:
IDH3A
Uniprot ID:
P50213
Molecular Weight:
39591.365 Da
References
  1. Soundar S, O'hagan M, Fomulu KS, Colman RF: Identification of Mn2+-binding aspartates from alpha, beta, and gamma subunits of human NAD-dependent isocitrate dehydrogenase. J Biol Chem. 2006 Jul 28;281(30):21073-81. Epub 2006 May 31. [16737955 ]
Target Details
6. Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial
General Function:
Nad binding
Specific Function:
Not Available
Gene Name:
IDH3G
Uniprot ID:
P51553
Molecular Weight:
42793.97 Da
References
  1. Soundar S, O'hagan M, Fomulu KS, Colman RF: Identification of Mn2+-binding aspartates from alpha, beta, and gamma subunits of human NAD-dependent isocitrate dehydrogenase. J Biol Chem. 2006 Jul 28;281(30):21073-81. Epub 2006 May 31. [16737955 ]
Target Details
7. Major prion protein
General Function:
Tubulin binding
Specific Function:
Its primary physiological function is unclear. Has cytoprotective activity against internal or environmental stresses. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (PubMed:12732622, PubMed:19936054, PubMed:20564047). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).
Gene Name:
PRNP
Uniprot ID:
P04156
Molecular Weight:
27661.21 Da
References
  1. Brazier MW, Davies P, Player E, Marken F, Viles JH, Brown DR: Manganese binding to the prion protein. J Biol Chem. 2008 May 9;283(19):12831-9. doi: 10.1074/jbc.M709820200. Epub 2008 Mar 10. [18332141 ]
Target Details
8. Putative testis-specific prion protein
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
PRNT
Uniprot ID:
Q86SH4
Molecular Weight:
10755.655 Da
References
  1. Brazier MW, Davies P, Player E, Marken F, Viles JH, Brown DR: Manganese binding to the prion protein. J Biol Chem. 2008 May 9;283(19):12831-9. doi: 10.1074/jbc.M709820200. Epub 2008 Mar 10. [18332141 ]
Target Details
9. Serotransferrin
General Function:
Transferrin receptor binding
Specific Function:
Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation.
Gene Name:
TF
Uniprot ID:
P02787
Molecular Weight:
77063.195 Da
References
  1. Golub MS, Han B, Keen CL: Aluminum alters iron and manganese uptake and regulation of surface transferrin receptors in primary rat oligodendrocyte cultures. Brain Res. 1996 May 6;719(1-2):72-7. [8782865 ]
Target Details
10. TGF-beta-activated kinase 1 and MAP3K7-binding protein 1
General Function:
Protein serine/threonine phosphatase activity
Specific Function:
May be an important signaling intermediate between TGFB receptors and MAP3K7/TAK1. May play an important role in mammalian embryogenesis.
Gene Name:
TAB1
Uniprot ID:
Q15750
Molecular Weight:
54643.655 Da
References
  1. Conner SH, Kular G, Peggie M, Shepherd S, Schuttelkopf AW, Cohen P, Van Aalten DM: TAK1-binding protein 1 is a pseudophosphatase. Biochem J. 2006 Nov 1;399(3):427-34. [16879102 ]