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T3D1131 - Manganese sulfate
| Record Information | |
|---|---|
| Version | 1.0 |
| Creation Date | 2009-06-19 21:58:20 UTC |
| Update Date | 2013-04-25 08:37:43 UTC |
| Accession Number | T3D1131 |
| Identification | |
| Common Name | Manganese sulfate |
| Description | Manganese sulfate is a sulfate of manganese. It is the precursor to manganese metal and many chemical compounds, such as manganese dioxide. Manganese is a naturally occurring metal with the symbol Mn and the atomic number 25. It does not occur naturally in its pure form, but is found in many types of rocks in combination with other substances such as oxygen, sulfur, or chlorine. Manganese occurs naturally in most foods and small amounts are needed to stay healthy, as manganese ions act as cofactors for a number of enzymes. (R441, R442, R451) |
| Compound Type |
|
| Chemical Structure |
|
| Synonyms |
|
| Chemical Formula | MnO4S |
| Average Molecular Weight | 151.001 |
| Monoisotopic Molecular Weight | 150.889778814 |
| Chemical IUPAC Name | manganese(II) sulfate |
| CAS Registry Number | 7785-87-7 |
| SMILES | [Mn++].[O-]S([O-])(=O)=O |
| InChI Identifier | InChI=1S/Mn.H2O4S/c;1-5(2,3)4/h;(H2,1,2,3,4)/q+2;/p-2 |
| InChI Key | InChIKey=SQQMAOCOWKFBNP-UHFFFAOYSA-L |
| Chemical Taxonomy | |
| Kingdom | Inorganic Compounds |
| Super Class | Mixed Metal/Non-metal Compounds |
| Class | Transition Metal Oxoanionic Compounds |
| Sub Class | Transition Metal Sulfates |
| Direct Parent | Transition Metal Sulfates |
| Alternative Parents | Not Available |
| Molecular Framework | Acyclic Compounds |
| Substituents | Not Available |
| External Descriptors | Not Available |
| External Links | |
| DrugBank ID | Not Available |
| PubChem Compound ID | 24580  |
| KEGG ID | Not Available |
| UniProt ID | Not Available |
| OMIM ID | Not Available |
| ChEBI ID | Not Available |
| BioCyc ID | Not Available |
| CTD ID | C039798 |
| Stitch ID | Manganese sulfate |
| PDB ID | Not Available |
| ACToR ID | 12206 |
| Wikipedia Link | Not Available |
| Physical Properties | |
| Appearance | Pale red solid. |
| Melting Point | 710 C (anhydrous) 27 C (tetrahydrate) |
| Solubility | Not Available |
| Predicted LogP | -0.8415520233333333 |
| Toxicity Profile | |
| Route of Exposure | Oral (R441) ; inhalation (R441) |
| Mechanism of Action | Manganese 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 perturbations other neurotransmitters, such as GABA and glutamate. In order to produce oxidative damage, manganese must first overwhelm the antioxidant enzyme manganese superoxide dismutase. 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. (R441) |
| Metabolism | Manganese is absorbed mainly 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 is capable of existing 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. (R441) |
| Toxicity Values | LD50: 305 mg/kg (Oral, Mouse) (R591) LD50: 64 mg/kg (Intraperitoneal, Mouse) (R591) LD50: 146 mg/kg (Subcutaneous, Mouse) (R591) |
| Lethal Dose | Not Available |
| Carcinogenicity (IARC Classification) | Not Available |
| Uses/Sources | Manganese sulfate is the precursor to manganese metal and many chemical compounds, such as manganese dioxide. (R451) |
| Minimum Risk Level | Chronic Inhalation: 0.0003 mg/m3 (R260) |
| Health Effects | Manganese 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 |
| Symptoms | Manganese 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 |
| Treatment | Not Available |
| References | |
| General References |
|
Targets
1. Aconitate hydratase, mitochondrial
Catalyzes the isomerization of citrate to isocitrate via cis-aconitate (By similarity).
Manganese interferes with amino acid metabolism by inhibiting aconitase, resulting in an increase in citrate levels. It is also believed that this direct disruption of the catalytic [4Fe-4S] cluster of aconitase by manganese produces iron regulary protein 1, resulting in alterations in cellular iron homeostasis. (R444)UniProt ID: Q99798
Gene: ACO2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R444 — 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 ]
2. Cytoplasmic aconitate hydratase
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 (By similarity).
Manganese interferes with amino acid metabolism by inhibiting aconitase, resulting in an increase in citrate levels. It is also believed that this direct disruption of the catalytic [4Fe-4S] cluster of aconitase by manganese produces iron regulary protein 1, resulting in alterations in cellular iron homeostasis. (R444)UniProt ID: P21399
Gene: ACO1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R444 — 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 ]
3. Iron-responsive element-binding protein 2
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
Manganese alters cellular iron homeostasis by stabilizing iron regulatory protein 2. This may occur by manganese competing directly for an iron-binding site on the iron binding protein, disrupting the cellular mechanisms responsible for its iron-dependent degradation. (R444)UniProt ID: P48200
Gene: IREB2
Protein Sequence: FASTA
SNPs: SNPJam Report
References:
- R444 — 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 ]
4. Major prion protein
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). 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).
Manganese binds to the prion protein, altering its conformation, displacing copper, and altering the redox chemistry of the metal-protein complex. These changes are similar to those associated with prion disease. (R443)UniProt ID: P04156
Gene: PRNP
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R443 — 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. Epub 2008 Mar 10.
[18332141 ]
5. Putative testis-specific prion protein
Manganese binds to the prion protein, altering its conformation, displacing copper, and altering the redox chemistry of the metal-protein complex. These changes are similar to those associated with prion disease. (R443)UniProt ID: Q86SH4
Gene: PRNT
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R443 — 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. Epub 2008 Mar 10.
[18332141 ]