Manganese cation

Identification

Summary

Manganese cation is a transition metal used for supplementation of manganese during Total Parenteral Nutrition (TPN).

Brand Names

Concept Ob, Multitrace-4, Multitrace-5, Multrys, Tandem Plus

Generic Name

Manganese cation

DrugBank Accession Number

DB06757

Background

Manganese is a transition metal that was first described in the 19th and 20th centuries.² It is environmentally abundant, being the fifth most abundant metal and the twelfth most abundant element overall on Earth.^2,4 Manganese intake primarily occurs through the diet,⁶ as it is found at low levels in many food sources and water.^6,3 In humans, manganese regulates several physiological processes by acting as a cofactor for proteins ^2,3,4 making it an essential metal for normal development and physiological functions.²

Manganese can be found in over-the-counter nutritional supplements and vitamins.⁴ It is commonly used in total parenteral nutrition (TPN) therapy.¹⁰ Apart from its use in human health, has been used in the mining industry, welding, smelting, and the manufacture of batteries.²

Type

Small Molecule

Groups

Approved, Nutraceutical

Structure

Similar Structures

Weight: Average: 54.938
Monoisotopic: 54.938049636
Chemical Formula: Mn

Synonyms

MANGANESE CATION (2+)
MANGANESE CATION (MN2+)
MANGANESE DICATION
MANGANESE ION(2+)
MANGANESE, ION (MN2+)
MANGANESE(2+)
MANGANESE(II)
MANGANESE(II) ION
MANGANOUS CATION

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Pharmacology

Indication

Intravenous manganese, alone or in combination with other trace elements, is indicated for total parenteral nutrition (TPN).^10,11

Administration helps to maintain manganese serum levels and prevent the depletion of endogenous stores and subsequent deficiency symptoms.¹⁰

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Prevention of	Manganese deficiency		••••••••••••
Treatment of	Manganese deficiency		••••••••••••

Associated Therapies

Contraindications & Blackbox Warnings

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Pharmacodynamics

Providing manganese (Mn) during TPN helps prevent the development of deficiency symptoms such as nausea and vomiting, weight loss, dermatitis, and changes in hair growth and colour.¹⁰

Mechanism of action

Mn²⁺ is an essential cofactor and activator for many enzymes that regulate biological functions and processes, such as oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases.³ These enzymes include polysaccharide polymerase, liver arginase, cholinesterase, pyruvate carboxylase,¹⁰ and Mn superoxide dismutase (MnSOD).⁸ These enzymes regulate immune function, metabolism, growth potential, hemostasis, mitochondrial homeostasis and antioxidant function,² and neuronal function.^4,8

Target	Actions	Organism
UIsocitrate dehydrogenase [NAD] subunit alpha, mitochondrial	cofactor	Humans
UIsocitrate dehydrogenase [NAD] subunit gamma, mitochondrial	cofactor	Humans
UTGF-beta-activated kinase 1 and MAP3K7-binding protein 1	Not Available	Humans
UArginase-1	cofactor	Humans
USuperoxide dismutase [Mn], mitochondrial	cofactor	Humans
UGlutamine synthetase	Not Available	Humans
UPhosphoenolpyruvate Carboxykinases	cofactor	Humans
USerine/threonine-protein phosphatase PP1-gamma catalytic subunit	cofactor	Humans

Absorption

When orally administered, manganese (Mn) is reported to be readily absorbed through the intestinal tract:^2,3 about 3–5% of dietary Mn is absorbed as Mn²⁺ and Mn⁴⁺.⁹

Under conditions of minimal intake, 20 mcg Mn/day is retained following intravenous administration. Assays for manganese in whole blood result in concentrations ranging from six to 12 mcg/Mn/L.¹⁰

Volume of distribution

Mn can cross the blood-brain barrier.^4,6 Manganese is widely distributed but concentrates in mitochondria-rich tissues such as the brain, kidney, pancreas, and liver.¹⁰

Protein binding

Manganese is reported to bind to a number of carriers, such as transmanganin, beta-globulin, and transferrin.⁹ It is also reported to bind to serum albumin but to a minimal extent.⁵

Metabolism

Mn²⁺ is oxidized to Mn³⁺ by liver and plasma ceruloplasmin.⁹

Route of elimination

Excretion of manganese occurs mainly through the bile, but in the event of an obstruction, ancillary excretion routes include pancreatic juice or return into the lumen of the duodenum, jejunum, or ileum. Urinary excretion of manganese is negligible.¹⁰

Half-life

Not Available

Clearance

Not Available

Adverse Effects

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Toxicity

There are many reported LD₅₀ values in animals. The LD50 in mice and rats exposed to manganese (Mn) via gavage ranged from 225 to 1,082 mg Mn/kg/day.¹²

While manganese is an essential metal for various biochemical processes, it is also associated with the potential to cause neurotoxicity, cardiotoxicity, and hepatotoxicity.² Manganese toxicity is rare, but it can arise from occupational, accidental, or iatrogenic exposures.^2,3 Acute manganese toxicity was reported in adult patients following infusion of manganese more than 10,000-fold the recommended dosage and after the use of dialysis fluid contaminated with manganese. Signs and symptoms included skin flushing, acute pancreatitis, elevated whole blood manganese concentrations, and magnetic resonance imaging (MRI) evidence of brain accumulation of manganese. Chronic infusion and oral intake of manganese above the recommended dosage have resulted in neuropsychiatric symptoms and MRI evidence of brain accumulation of manganese.¹⁰ Manganese-induced neurotoxicity is associated with motor dysfunction syndrome or Parkinsonism.^3,6,7

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions: This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions: No interactions found.

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Manganese chloride	6YB4901Y90	7773-01-5	GLFNIEUTAYBVOC-UHFFFAOYSA-L
Manganese chloride tetrahydrate	QQE170PANO	13446-34-9	CNFDGXZLMLFIJV-UHFFFAOYSA-L
Manganese sulfate	W00LYS4T26	10034-96-5	ISPYRSDWRDQNSW-UHFFFAOYSA-L

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Manganese	Injection, solution	0.1 mg/1mL	Intravenous	Hospira, Inc.	2005-01-31	Not applicable
Manganese Sulfate	Injection, solution	0.1 mg/1mL	Intravenous	AMERICAN REGENT, INC.	1990-09-30	Not applicable
Micro Mn	Solution	0.5 mg / mL	Intravenous	Sandoz Canada Incorporated	1992-12-31	2018-08-01
Micro Mn	Solution	0.1 mg / mL	Intravenous	Sandoz Canada Incorporated	1992-12-31	Not applicable

Over the Counter Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Bio-plex Tab 0.95mg	Tablet	.95 mg / tab	Oral	Therapeutic Foods Co.	1988-12-31	2001-07-31
Chelated Manganese Tablets - 5mg	Tablet	5 mg	Oral	Albion	1996-09-06	2002-07-12
Chelazome Manganese Cap 15mg	Capsule	15 mg	Oral	Trophic Canada Ltd.	1987-12-31	2008-08-28
Hvp Chelated Manganese 30mg	Tablet	30 mg / tab	Oral	Swiss Herbal Remedies Ltd.	1999-09-16	2003-09-10
Manganese	Capsule	30 mg	Oral	Seroyal International Inc.	1993-12-31	2009-07-06

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
24 Multivitamins + Minerals	Manganese cation (2 mg) + Ascorbic acid (150 mg) + Beta carotene (10000 unit) + Biotin (25 mcg) + Calcium (130 mg) + Cholecalciferol (400 unit) + Choline bitartrate (25 mg) + Chromium (20 mcg) + Copper (1 mg) + Cyanocobalamin (25 mcg) + Ferrous fumarate (15 mg) + Folic acid (.8 mg) + Inositol (25 mg) + Magnesium (65 mg) + Molybdenum (20 mcg) + Niacin (25 mg) + Calcium pantothenate (25 mg) + Potassium (15 mg) + Potassium Iodide (.1 mg) + Pyridoxine hydrochloride (25 mg) + Racemethionine (25 mg) + Riboflavin (25 mg) + Selenium (20 mcg) + Thiamine hydrochloride (25 mg) + Vanadium (20 mcg) + Vitamin A palmitate (5000 unit) + Vitamin E (50 unit) + Zinc (10 mg)	Tablet	Oral	Stanley Pharmaceuticals, A Division Of Vita Health Products Inc.	1997-04-30	2002-07-31
50 Plus Multiple Vitamins & Minerals	Manganese cation (5 mg) + Ascorbic acid (90 mg) + Biotin (45 mcg) + Calcium (200 mg) + Cholecalciferol (400 unit) + Chromium (10 mcg) + Copper (2 mg) + Cyanocobalamin (25 mcg) + Folic acid (0.4 mg) + Magnesium (100 mg) + Molybdenum (25 mcg) + Nicotinamide (40 mg) + Pantothenic acid (10 mg) + Potassium Iodide (0.15 mg) + Pyridoxine hydrochloride (3 mg) + Riboflavin (3.2 mg) + Selenium (25 mcg) + Thiamine mononitrate (2.25 mg) + Vanadium (10 mcg) + Vitamin A palmitate (6000 unit) + Zinc (15 mg)	Tablet	Oral	Gfr Pharma Ltd.	2002-10-20	2004-06-15
A.R.T.H. Away Formula	Manganese cation (0.58 mg) + Calcium (24 mg) + Cholecalciferol (45 unit) + Copper (0.232 mg) + Folic acid (0.025 mg) + Pyridoxine hydrochloride (0.5 mg) + Selenium (1.54 mcg) + Zinc (0.63 mg)	Capsule	Oral	Abundance Naturally Ltd	1999-02-01	2006-06-16
A/o-26 - Caplet	Manganese cation (2.5 mg) + Beta carotene (7500 unit) + Calcium (75 mg) + Calcium ascorbate (250 mg) + Copper (1 mg) + DL-alpha tocopheryl acetate (100 unit) + Folic acid (.4 mg) + Racemethionine (50 mg) + Selenium (100 mcg) + Zinc (7.5 mg)	Tablet	Oral	Enviro Tech International Canada	1996-12-19	1999-07-26
Acti-MN + B1 + C Caplet	Manganese cation (30.0 mg) + Calcium ascorbate (100 mg) + Thiamine hydrochloride (20 mg)	Tablet	Oral	Acti Form Ltd.	1991-12-31	2005-03-21

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Addamel N	Manganese chloride tetrahydrate (0.027 mg/1mL) + Chromic chloride hexahydrate (1 ug/1mL) + Cuprous chloride (0.13 mg/1mL) + Ferric chloride (0.11 mg/1mL) + Potassium Iodide (0.013 mg/1mL) + Sodium selenite (3.2 ug/1mL) + Sodium fluoride (0.095 mg/1mL) + Sodium molybdate dihydrate (1.9 ug/1mL) + Zinc chloride (0.65 mg/1mL)	Injection, solution	Intravenous	Fresenius Kabi USA, LLC	2013-05-07	2017-03-31
ADDAMEL N 20 AMPUL	Manganese chloride (990 mcg/10mL) + Chromic chloride (53.3 mcg/10mL) + Cupric Chloride (3.4 mg/10mL) + Ferric chloride (5.4 mg/10mL) + Potassium Iodide (166 mcg/10mL) + Sodium selenite (69 mcg/10mL) + Sodium fluoride (2.1 mg/10mL) + Sodium molybdate (48.5 mcg/10mL) + Zinc chloride (13.6 mg/10mL)	Injection, solution	Intravenous	FRESENİUS KABİ İLAÇ SAN. VE TİC. LTD. ŞTİ.	2019-04-30	Not applicable
ADDAVEN IV INFUZYON ICIN KONSANTRE SOLUSYON	Manganese chloride (198 mcg/10mL) + Chromic chloride (53.3 mcg/10mL) + Cupric Chloride (1.02 mg/10mL) + Ferric chloride (5.4 mg/10mL) + Potassium Iodide (166 mcg/10mL) + Sodium selenite (173 mcg/10mL) + Sodium fluoride (2.1 mg/10mL) + Sodium molybdate (48.5 mcg/10mL) + Zinc chloride (10.5 mg/10mL)	Injection, solution	Intravenous	FRESENİUS KABİ İLAÇ SAN. VE TİC. LTD. ŞTİ.	2016-09-06	2022-11-10
Centratex	Manganese sulfate (1.3 mg/1) + Cupric sulfate (0.8 mg/1) + Cyanocobalamin (15 ug/1) + Folic acid (1 mg/1) + Iron (106 mg/1) + Magnesium sulfate (6.9 mg/1) + Nicotinamide (30 mg/1) + Calcium pantothenate (10 mg/1) + Pyridoxine hydrochloride (5 mg/1) + Riboflavin (6 mg/1) + Sodium ascorbate (200 mg/1) + Thiamine mononitrate (10 mg/1) + Zinc sulfate, unspecified form (18.2 mg/1)	Capsule	Oral	Centurion Labs, LLC	2009-06-14	Not applicable
Concept OB	Manganese sulfate (1.3 mg/1) + Ascorbic acid (210 mg/1) + Biotin (300 ug/1) + Cupric sulfate pentahydrate (800 ug/1) + Cyanocobalamin (10 ug/1) + Ferrous fumarate (42.5 mg/1) + Folic acid (1 mg/1) + Iron (42.5 mg/1) + Magnesium sulfate (6.9 mg/1) + Niacin (20 mg/1) + Calcium pantothenate (7 mg/1) + Pyridoxine hydrochloride (25 mg/1) + Riboflavin (5 mg/1) + Thiamine mononitrate (5 mg/1) + Zinc sulfate, unspecified form (18.2 mg/1)	Capsule	Oral	U.S. Pharmaceutical Corporation	2009-01-01	Not applicable

Chemical Identifiers

UNII: H6EP7W5457
CAS number: 16397-91-4
InChI Key: WAEMQWOKJMHJLA-UHFFFAOYSA-N
InChI: InChI=1S/Mn/q+2
IUPAC Name: manganese(2+) ion
SMILES: [Mn++]

References

General References

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. [Article]
Evans GR, Masullo LN: Manganese Toxicity. . [Article]
Li L, Yang X: The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions. Oxid Med Cell Longev. 2018 Apr 5;2018:7580707. doi: 10.1155/2018/7580707. eCollection 2018. [Article]
Horning KJ, Caito SW, Tipps KG, Bowman AB, Aschner M: Manganese Is Essential for Neuronal Health. Annu Rev Nutr. 2015;35:71-108. doi: 10.1146/annurev-nutr-071714-034419. Epub 2015 May 13. [Article]
Scheuhammer AM, Cherian MG: Binding of manganese in human and rat plasma. Biochim Biophys Acta. 1985 Jun 18;840(2):163-9. doi: 10.1016/0304-4165(85)90115-1. [Article]
Aschner M, Dorman DC: Manganese: pharmacokinetics and molecular mechanisms of brain uptake. Toxicol Rev. 2006;25(3):147-54. doi: 10.2165/00139709-200625030-00002. [Article]
Kulshreshtha D, Ganguly J, Jog M: Manganese and Movement Disorders: A Review. J Mov Disord. 2021 May;14(2):93-102. doi: 10.14802/jmd.20123. Epub 2021 Apr 6. [Article]
Chen P, Bornhorst J, Aschner M: Manganese metabolism in humans. Front Biosci (Landmark Ed). 2018 Mar 1;23:1655-1679. doi: 10.2741/4665. [Article]
Avila DS, Puntel RL, Aschner M: Manganese in health and disease. Met Ions Life Sci. 2013;13:199-227. doi: 10.1007/978-94-007-7500-8_7. [Article]
FDA Approved Drug Products: Manganese Chloride Intravenous Injection (December 2023) [Link]
FDA Approved Drug Products: MULTRYS (trace elements injection 4*), for intravenous use (June 2021) [Link]
Agency for Toxic Substances and Disease Registry: Toxicological Profile for Manganese [Link]

External Links

Human Metabolome Database: HMDB0001333
KEGG Drug: D04854
KEGG Compound: C19610
PubChem Compound: 27854
PubChem Substance: 310264880
ChemSpider: 25916
RxNav: 1546272
ChEBI: 29035
ChEMBL: CHEMBL2103742
PDBe Ligand: MN
Drugs.com: Drugs.com Drug Page
Wikipedia: Manganese

PDB Entries

117e / 1a0d / 1a0o / 1a16 / 1a3w / 1a3x / 1a5v / 1a6q / 1a76 / 1a9x …

show 4452 more

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Not Yet Recruiting	Treatment	Manganese Safety in Adults	1
4	Not Yet Recruiting	Treatment	Manganese Safety in Pediatric Patients	1
2	Completed	Treatment	Central Serous Chorioretinopathy (CSC)	1
2	Completed	Treatment	Ovarian Cancer	1
2, 3	Completed	Treatment	Substance Abuse / Substance Dependence	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection	Intravenous	5.33 mcg/ml
Injection, solution	Intravenous drip
Solution	Intravenous	5.33 mcg/ml
Tablet	Oral	.95 mg / tab
Tablet	Oral	5 mg
Capsule	Oral	15 mg
Tablet, extended release	Oral
Tablet, film coated
Tablet, coated	Oral
Tablet
Capsule
Capsule	Cutaneous; Oral
Liquid	Oral
Tablet, delayed release	Oral
Capsule	Oral
Powder	Oral
Tablet, effervescent	Oral
Capsule, coated	Oral
Capsule	Oral	30 mg
Tablet	Oral	30 mg / tab
Tablet	Oral	15 mg / tab
Tablet	Oral	50 mg / tab
Injection, solution	Intravenous	0.1 mg/1mL
Kit	Oral
Tablet, film coated	Oral
Solution	Intravenous	0.1 mg / mL
Solution	Intravenous	0.5 mg / mL
Liquid	Intravenous
Injection, solution, concentrate	Intravenous
Injection, solution	Intravenous
Capsule, liquid filled	Oral
Solution	Intravenous	0.053 mg/10ml
Solution	Oral
Tablet	Oral	6 mg / tab
Tablet	Oral	4 mg / tab
Injection, solution, concentrate	Intravenous; Parenteral
Injection, solution, concentrate	Parenteral
Solution, concentrate	Intravenous
Injection	Intravenous
Tablet, chewable	Oral
Tablet	Oral
Capsule, gelatin coated	Oral
Solution	Intravenous
Injection, solution	Parenteral
Powder, for solution	Oral
Tablet	Oral	300.000 mg
Tablet, sugar coated	Oral

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US11786548	No	2021-07-01	2041-07-01

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	1246	Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL 2005, p. 4-72
boiling point (°C)	2061	Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL 2005, p. 4-72

Predicted Properties

Property	Value	Source
logP	-0.16	Chemaxon
pKa (Strongest Acidic)	3.09	Chemaxon
Physiological Charge	2	Chemaxon
Hydrogen Acceptor Count	0	Chemaxon
Hydrogen Donor Count	0	Chemaxon
Polar Surface Area	0 Å²	Chemaxon
Rotatable Bond Count	0	Chemaxon
Refractivity	0 m³·mol^-1	Chemaxon
Polarizability	1.78 Å³	Chemaxon
Number of Rings	0	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	Yes	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST): Not Available
Spectra: Not Available
Chromatographic Properties: Collision Cross Sections (CCS)
Not Available

Targets

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Details1. Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Cofactor

General Function: Nad binding
Specific Function: Not Available
Gene Name: IDH3A
Uniprot ID: P50213
Uniprot Name: Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial
Molecular Weight: 39591.365 Da

References

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. [Article]
Bailey JM, Colman RF: Distances among coenzyme and metal sites of NADP+-dependent isocitrate dehydrogenase using resonance energy transfer. Biochemistry. 1987 Jul 28;26(15):4893-900. doi: 10.1021/bi00389a042. [Article]

Details2. Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Cofactor

General Function: Nad binding
Specific Function: Not Available
Gene Name: IDH3G
Uniprot ID: P51553
Uniprot Name: Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial
Molecular Weight: 42793.97 Da

References

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. [Article]
Bailey JM, Colman RF: Distances among coenzyme and metal sites of NADP+-dependent isocitrate dehydrogenase using resonance energy transfer. Biochemistry. 1987 Jul 28;26(15):4893-900. doi: 10.1021/bi00389a042. [Article]

Details3. TGF-beta-activated kinase 1 and MAP3K7-binding protein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

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
Uniprot Name: TGF-beta-activated kinase 1 and MAP3K7-binding protein 1
Molecular Weight: 54643.655 Da

References

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. [Article]

Details4. Arginase-1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Cofactor

General Function: Manganese ion binding
Specific Function: Not Available
Gene Name: ARG1
Uniprot ID: P05089
Uniprot Name: Arginase-1
Molecular Weight: 34734.655 Da

References

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. [Article]
Li L, Yang X: The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions. Oxid Med Cell Longev. 2018 Apr 5;2018:7580707. doi: 10.1155/2018/7580707. eCollection 2018. [Article]

Details5. Superoxide dismutase [Mn], mitochondrial

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Cofactor

General Function: Superoxide dismutase activity
Specific Function: Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.
Gene Name: SOD2
Uniprot ID: P04179
Uniprot Name: Superoxide dismutase [Mn], mitochondrial
Molecular Weight: 24721.955 Da

References

Li L, Yang X: The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions. Oxid Med Cell Longev. 2018 Apr 5;2018:7580707. doi: 10.1155/2018/7580707. eCollection 2018. [Article]

Details6. Glutamine synthetase

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Manganese ion binding
Specific Function: This enzyme has 2 functions: it catalyzes the production of glutamine and 4-aminobutanoate (gamma-aminobutyric acid, GABA), the latter in a pyridoxal phosphate-independent manner (By similarity). E...
Gene Name: GLUL
Uniprot ID: P15104
Uniprot Name: Glutamine synthetase
Molecular Weight: 42064.15 Da

References

Li L, Yang X: The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions. Oxid Med Cell Longev. 2018 Apr 5;2018:7580707. doi: 10.1155/2018/7580707. eCollection 2018. [Article]
Avila DS, Puntel RL, Aschner M: Manganese in health and disease. Met Ions Life Sci. 2013;13:199-227. doi: 10.1007/978-94-007-7500-8_7. [Article]

Details7. Phosphoenolpyruvate Carboxykinases (Protein Group)

Kind: Protein group
Organism: Humans
Pharmacological action: Unknown
Actions: Cofactor

General Function: Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle.
Specific Function: Gtp binding

Components:

Name	UniProt ID
Phosphoenolpyruvate carboxykinase [GTP], mitochondrial	Q16822
Phosphoenolpyruvate carboxykinase, cytosolic [GTP]	P35558

References

Li L, Yang X: The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions. Oxid Med Cell Longev. 2018 Apr 5;2018:7580707. doi: 10.1155/2018/7580707. eCollection 2018. [Article]

Details8. Serine/threonine-protein phosphatase PP1-gamma catalytic subunit

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Cofactor

General Function: Protein serine/threonine phosphatase activity
Specific Function: Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essent...
Gene Name: PPP1CC
Uniprot ID: P36873
Uniprot Name: Serine/threonine-protein phosphatase PP1-gamma catalytic subunit
Molecular Weight: 36983.4 Da

References

Avila DS, Puntel RL, Aschner M: Manganese in health and disease. Met Ions Life Sci. 2013;13:199-227. doi: 10.1007/978-94-007-7500-8_7. [Article]

Enzymes

Details1. Cytoplasmic aconitate hydratase

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

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 whe...
Gene Name: ACO1
Uniprot ID: P21399
Uniprot Name: Cytoplasmic aconitate hydratase
Molecular Weight: 98398.14 Da

References

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. [Article]

Carriers

Details1. Serotransferrin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Binder

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 si...
Gene Name: TF
Uniprot ID: P02787
Uniprot Name: Serotransferrin
Molecular Weight: 77063.195 Da

References

Scheuhammer AM, Cherian MG: Binding of manganese in human and rat plasma. Biochim Biophys Acta. 1985 Jun 18;840(2):163-9. doi: 10.1016/0304-4165(85)90115-1. [Article]
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. [Article]
Avila DS, Puntel RL, Aschner M: Manganese in health and disease. Met Ions Life Sci. 2013;13:199-227. doi: 10.1007/978-94-007-7500-8_7. [Article]
FDA Approved Drug Products: Manganese Chloride Intravenous Injection (December 2023) [Link]

Details2. Serum albumin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Binder

General Function: Toxic substance binding
Specific Function: Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name: ALB
Uniprot ID: P02768
Uniprot Name: Serum albumin
Molecular Weight: 69365.94 Da

References

Scheuhammer AM, Cherian MG: Binding of manganese in human and rat plasma. Biochim Biophys Acta. 1985 Jun 18;840(2):163-9. doi: 10.1016/0304-4165(85)90115-1. [Article]
Avila DS, Puntel RL, Aschner M: Manganese in health and disease. Met Ions Life Sci. 2013;13:199-227. doi: 10.1007/978-94-007-7500-8_7. [Article]

Details3. Ceruloplasmin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Binder

General Function: Ferroxidase activity
Specific Function: Ceruloplasmin is a blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iro...
Gene Name: CP
Uniprot ID: P00450
Uniprot Name: Ceruloplasmin
Molecular Weight: 122204.45 Da

References

Horning KJ, Caito SW, Tipps KG, Bowman AB, Aschner M: Manganese Is Essential for Neuronal Health. Annu Rev Nutr. 2015;35:71-108. doi: 10.1146/annurev-nutr-071714-034419. Epub 2015 May 13. [Article]

Transporters

Details1. Zinc transporter ZIP14

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Broad-scope metal ion transporter with a preference for zinc uptake (PubMed:29621230). Also mediates cellular uptake of nontransferrin-bound iron.
Specific Function: Ferrous iron transmembrane transporter activity
Gene Name: SLC39A14
Uniprot ID: Q15043
Uniprot Name: Zinc transporter ZIP14
Molecular Weight: 54211.785 Da

References

Xin Y, Gao H, Wang J, Qiang Y, Imam MU, Li Y, Wang J, Zhang R, Zhang H, Yu Y, Wang H, Luo H, Shi C, Xu Y, Hojyo S, Fukada T, Min J, Wang F: Manganese transporter Slc39a14 deficiency revealed its key role in maintaining manganese homeostasis in mice. Cell Discov. 2017 Jul 18;3:17025. doi: 10.1038/celldisc.2017.25. eCollection 2017. [Article]
Mercadante CJ, Prajapati M, Conboy HL, Dash ME, Herrera C, Pettiglio MA, Cintron-Rivera L, Salesky MA, Rao DB, Bartnikas TB: Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity. J Clin Invest. 2019 Dec 2;129(12):5442-5461. doi: 10.1172/JCI129710. [Article]

Details2. Natural resistance-associated macrophage protein 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Zinc ion transmembrane transporter activity
Specific Function: Important in metal transport, in particular iron. Can also transport manganese, cobalt, cadmium, nickel, vanadium and lead. Involved in apical iron uptake into duodenal enterocytes. Involved in iro...
Gene Name: SLC11A2
Uniprot ID: P49281
Uniprot Name: Natural resistance-associated macrophage protein 2
Molecular Weight: 62265.195 Da

References

Horning KJ, Caito SW, Tipps KG, Bowman AB, Aschner M: Manganese Is Essential for Neuronal Health. Annu Rev Nutr. 2015;35:71-108. doi: 10.1146/annurev-nutr-071714-034419. Epub 2015 May 13. [Article]

Details3. Zinc transporter 10

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Plays a pivotal role in manganese transport. Manganese is an essential cation for the function of several enzymes, including some crucially important for the metabolism of neurotransmitters and other neuronal metabolic pathways. However, elevated levels of manganese are cytotoxic and induce oxidative stress, mitochondrial dysfunction and apoptosis. Acts as manganese efflux transporter and confers protection against manganese-induced cell death (PubMed:22341972, PubMed:22341971, PubMed:25319704, PubMed:27226609, PubMed:27307044). Also acts as zinc transporter involved in zinc homeostasis. Seems to mediate zinc transport into early endosomes and recycling endosomes to prevent zinc toxicity; the function may be regulated by heterodimerization with other zinc transporters of the SLC30A subfamily. The SLC30A3:SLC30A10 heterodimer is involved in zinc transport-dependent regulation of the EGFR/ERK transduction pathway in endosomes. May be involved in regulation of zinc-dependent senescence of vascular smooth muscle cells (PubMed:22706290, PubMed:22427991, PubMed:26728129).
Specific Function: Manganese ion transmembrane transporter activity
Gene Name: SLC30A10
Uniprot ID: Q6XR72
Uniprot Name: Zinc transporter 10
Molecular Weight: 52683.46 Da

References

Horning KJ, Caito SW, Tipps KG, Bowman AB, Aschner M: Manganese Is Essential for Neuronal Health. Annu Rev Nutr. 2015;35:71-108. doi: 10.1146/annurev-nutr-071714-034419. Epub 2015 May 13. [Article]

Details4. Transient receptor potential cation channel subfamily M member 7

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Protein serine/threonine kinase activity
Specific Function: Essential ion channel and serine/threonine-protein kinase. Divalent cation channel permeable to calcium and magnesium. Has a central role in magnesium ion homeostasis and in the regulation of anoxi...
Gene Name: TRPM7
Uniprot ID: Q96QT4
Uniprot Name: Transient receptor potential cation channel subfamily M member 7
Molecular Weight: 212695.37 Da

References

Avila DS, Puntel RL, Aschner M: Manganese in health and disease. Met Ions Life Sci. 2013;13:199-227. doi: 10.1007/978-94-007-7500-8_7. [Article]

Drug created at September 14, 2010 16:21 / Updated at May 17, 2024 18:09

Manganese cation

Identification

Structure for Manganese cation (DB06757)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

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Clinical Trials

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

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Components:

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Enzymes

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Carriers

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Transporters

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