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Record Information
Version5.0
StatusDetected and Quantified
Creation Date2007-04-12 18:30:36 UTC
Update Date2020-02-26 21:26:09 UTC
HMDB IDHMDB0005949
Secondary Accession Numbers
  • HMDB05949
Metabolite Identification
Common NameLithium
DescriptionLithium (Li) is an alkali metal. First described as a mood stabilizer in 1949, it remains an efficacious treatment for bipolar disorders. Recent emerging evidence of its neuroprotective and neurogenic effects alludes to lithium's potential therapeutic use in stroke and neurodegenerative diseases. One intriguing clinical application is in the treatment of Alzheimer's disease. Ongoing clinical trials are evaluating lithium's abilities to lower tau and beta-amyloid levels in cerebrospinal fluid in Alzheimer's patients. Lithium reduces brain inositol levels by inhibiting the enzyme inositol monophosphatase. This suggests that inositol monophosphatase inhibition is a key mechanism of Li's therapeutic action and that design of new inositol monophosphatase inhibitors may be a practical strategy to create new compounds with Li-like therapeutic effects. Lithium reduces the severity of some behavioral complications of Alzheimer's disease (AD). And there are growing indications that Li may be of benefit to the underlying pathology of AD, as well as an array of other common CNS disorders, including stroke, Parkinson's disease, and Huntington's disease. Physiologically, it exists as an ion in the body. Despite these demonstrated and prospective therapeutic benefits, Li's mechanism of action remains elusive, and opinions differ regarding the most relevant molecular targets. Lithium inhibits several enzymes; significant among these are inositol monophosphatase (IMPase), glycogen synthase kinase-3 (GSK-3), and the proteasome. Lithium has a narrow therapeutic range, and several well characterised adverse effects limit the potential usefulness of higher doses. Acute ingestion in Li-naive patients is generally associated with only short-lived exposure to high concentrations, due to extensive distribution of Li throughout the total body water compartment. Conversely, chronic toxicity and acute-on-therapeutic ingestion are associated with prolonged exposure to higher tissue concentrations and, therefore, greater toxicity. Lithium toxicity may be life threatening, or result in persistent cognitive and neurological impairment. Therefore, enhanced Li clearance has been explored as a means of minimizing exposure to high tissue concentrations. Although haemodialysis is highly effective in removing circulating Li, serum concentrations often rebound so repeated or prolonged treatment may be required. Continuous arteriovenous haemodiafiltration and continuous venovenous haemodiafiltration increase Li clearance, albeit to a lesser extent than haemodialysis, and are more widely accessible. Lithium reduces brain inositol levels by inhibiting IMPase, suggesting that IMPase's inhibition is a key mechanism of Li's therapeutic action and that design of new IMPase inhibitors may be a practical strategy to create new compounds with Li-like therapeutic effects. (PMID: 17688381 , 17316163 , 8110911 , 17288494 ).
Structure
Data?1582752369
Synonyms
ValueSource
Li(+)ChEBI
Lithium cationChEBI
LITHIUM ionChEBI
Lithium, ionChEBI
Lithium, ion (li1+)ChEBI
LiHMDB
Li(+) cationHMDB
Li(+) ionHMDB
Lithium atomHMDB
Lithium elementHMDB
Chemical FormulaLi
Average Molecular Weight6.941
Monoisotopic Molecular Weight7.016004049
IUPAC Namelithium(1+) ion
Traditional Namelithium(1+) ion
CAS Registry Number7439-93-2
SMILES
[Li+]
InChI Identifier
InChI=1S/Li/q+1
InChI KeyHBBGRARXTFLTSG-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of inorganic compounds known as homogeneous alkali metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a alkali metal atom.
KingdomInorganic compounds
Super ClassHomogeneous metal compounds
ClassHomogeneous alkali metal compounds
Sub ClassNot Available
Direct ParentHomogeneous alkali metal compounds
Alternative ParentsNot Available
Substituents
  • Homogeneous alkali metal
Molecular FrameworkNot Available
External Descriptors
Ontology
Physiological effectNot Available
Disposition
Biological locationSource
Process
Role
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point190 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
logP0ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity0 m³·mol⁻¹ChemAxon
Polarizability1.78 ųChemAxon
Number of Rings0ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M+H]+109.70530932474
DeepCCS[M-H]-107.98230932474
DeepCCS[M-2H]-143.21630932474
DeepCCS[M+Na]+116.53130932474

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
Lithium[Li+]710.2Standard polar33892256
Lithium[Li+]203.7Standard non polar33892256
Lithium[Li+]59.9Semi standard non polar33892256
Spectra

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lithium 10V, Positive-QTOFsplash10-0a4i-9000000000-d37172edddcf6ff278792015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lithium 20V, Positive-QTOFsplash10-0a4i-9000000000-d37172edddcf6ff278792015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lithium 40V, Positive-QTOFsplash10-0a4i-9000000000-d37172edddcf6ff278792015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lithium 10V, Negative-QTOFsplash10-0a4i-9000000000-00619c7d65eb4b7f8f3d2015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lithium 20V, Negative-QTOFsplash10-0a4i-9000000000-00619c7d65eb4b7f8f3d2015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lithium 40V, Negative-QTOFsplash10-0a4i-9000000000-00619c7d65eb4b7f8f3d2015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lithium 10V, Positive-QTOFsplash10-0a4i-9000000000-29e69b4fc922829a038d2021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lithium 20V, Positive-QTOFsplash10-0a4i-9000000000-29e69b4fc922829a038d2021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lithium 40V, Positive-QTOFsplash10-0a4i-9000000000-29e69b4fc922829a038d2021-09-24Wishart LabView Spectrum
Biological Properties
Cellular LocationsNot Available
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.040-0.240 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.14 +/- 0.10 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified10.383 +/- 4.679 uMAdult (>18 years old)Not SpecifiedNormal details
SalivaDetected and Quantified92.206-1844.115 uMAdult (>18 years old)Not Specified
Normal
details
SalivaDetected and Quantified2.537 +/- 0.793 uMAdult (>18 years old)BothNormal
    • Zerihun T. Dame, ...
details
UrineDetected and Quantified0.5 (0.2-0.9) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified0.504 (0.058-3.414) umol/mmol creatinineAdult (>18 years old)Not SpecifiedNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.12 +/- 0.05 uMAdult (>18 years old)BothMultiple sclerosis details
BloodDetected and Quantified0.11 +/- 0.085 uMAdult (>18 years old)BothParkinson's disease details
BloodDetected and Quantified0.16 +/- 0.074 uMElderly (>65 years old)BothAlzheimer's disease details
SalivaDetected and Quantified750 +/- 260 uMAdult (>18 years old)Male
Mental disorder
details
SalivaDetected and Quantified760 +/- 230 uMAdult (>18 years old)Female
Mental disorder
details
Associated Disorders and Diseases
Disease References
Alzheimer's disease
  1. Bocca B, Forte G, Petrucci F, Pino A, Marchione F, Bomboi G, Senofonte O, Giubilei F, Alimonti A: Monitoring of chemical elements and oxidative damage in patients affected by Alzheimer's disease. Ann Ist Super Sanita. 2005;41(2):197-203. [PubMed:16244393 ]
Multiple sclerosis
  1. Forte G, Visconti A, Santucci S, Ghazaryan A, Figa-Talamanca L, Cannoni S, Bocca B, Pino A, Violante N, Alimonti A, Salvetti M, Ristori G: Quantification of chemical elements in blood of patients affected by multiple sclerosis. Ann Ist Super Sanita. 2005;41(2):213-6. [PubMed:16244395 ]
Parkinson's disease
  1. Forte G, Alimonti A, Pino A, Stanzione P, Brescianini S, Brusa L, Sancesario G, Violante N, Bocca B: Metals and oxidative stress in patients with Parkinson's disease. Ann Ist Super Sanita. 2005;41(2):189-95. [PubMed:16244392 ]
Associated OMIM IDs
DrugBank IDDB01356
Phenol Explorer Compound IDNot Available
FooDB IDFDB004181
KNApSAcK IDNot Available
Chemspider ID26502
KEGG Compound IDC15473
BioCyc IDLI%2b
BiGG IDNot Available
Wikipedia LinkLithium
METLIN IDNot Available
PubChem Compound28486
PDB IDLI
ChEBI ID49713
Food Biomarker OntologyNot Available
VMH IDM02382
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Zhong J, Lee WH: Lithium: a novel treatment for Alzheimer's disease? Expert Opin Drug Saf. 2007 Jul;6(4):375-83. [PubMed:17688381 ]
  2. Aghdam SY, Barger SW: Glycogen synthase kinase-3 in neurodegeneration and neuroprotection: lessons from lithium. Curr Alzheimer Res. 2007 Feb;4(1):21-31. [PubMed:17316163 ]
  3. Kofman O, Belmaker RH: Ziskind-Somerfeld Research Award 1993. Biochemical, behavioral, and clinical studies of the role of inositol in lithium treatment and depression. Biol Psychiatry. 1993 Dec 15;34(12):839-52. [PubMed:8110911 ]
  4. Waring WS: Management of lithium toxicity. Toxicol Rev. 2006;25(4):221-30. [PubMed:17288494 ]
  5. Quiroz JA, Machado-Vieira R, Zarate CA Jr, Manji HK: Novel insights into lithium's mechanism of action: neurotrophic and neuroprotective effects. Neuropsychobiology. 2010;62(1):50-60. doi: 10.1159/000314310. Epub 2010 May 7. [PubMed:20453535 ]

Enzymes

General function:
Involved in inositol or phosphatidylinositol phosphatase activity
Specific function:
Converts adenosine 3'-phosphate 5'-phosphosulfate (PAPS) to adenosine 5'-phosphosulfate (APS) and 3'(2')-phosphoadenosine 5'- phosphate (PAP) to AMP. Has 1000-fold lower activity towards inositol 1,4-bisphosphate (Ins(1,4)P2) and inositol 1,3,4-trisphosphate (Ins(1,3,4)P3), but does not hydrolyze Ins(1)P, Ins(3,4)P2, Ins(1,3,4,5)P4 or InsP6.
Gene Name:
BPNT1
Uniprot ID:
O95861
Molecular weight:
33392.035
General function:
Involved in inositol or phosphatidylinositol phosphatase activity
Specific function:
Not Available
Gene Name:
INPP1
Uniprot ID:
P49441
Molecular weight:
43997.62
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Li Z, Stieglitz KA, Shrout AL, Wei Y, Weis RM, Stec B, Roberts MF: Mobile loop mutations in an archaeal inositol monophosphatase: modulating three-metal ion assisted catalysis and lithium inhibition. Protein Sci. 2010 Feb;19(2):309-18. doi: 10.1002/pro.315. [PubMed:20027624 ]
General function:
Involved in inositol or phosphatidylinositol phosphatase activity
Specific function:
Responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain. Can use myo-inositol monophosphates, myo-inositol 1,3-diphosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates.
Gene Name:
IMPA1
Uniprot ID:
P29218
Molecular weight:
36694.375
References
  1. Sarkar S, Rubinsztein DC: Inositol and IP3 levels regulate autophagy: biology and therapeutic speculations. Autophagy. 2006 Apr-Jun;2(2):132-4. Epub 2006 Apr 6. [PubMed:16874097 ]
  2. Trinquet E, Fink M, Bazin H, Grillet F, Maurin F, Bourrier E, Ansanay H, Leroy C, Michaud A, Durroux T, Maurel D, Malhaire F, Goudet C, Pin JP, Naval M, Hernout O, Chretien F, Chapleur Y, Mathis G: D-myo-inositol 1-phosphate as a surrogate of D-myo-inositol 1,4,5-tris phosphate to monitor G protein-coupled receptor activation. Anal Biochem. 2006 Nov 1;358(1):126-35. Epub 2006 Aug 30. [PubMed:16965760 ]
  3. Ohnishi T, Ohba H, Seo KC, Im J, Sato Y, Iwayama Y, Furuichi T, Chung SK, Yoshikawa T: Spatial expression patterns and biochemical properties distinguish a second myo-inositol monophosphatase IMPA2 from IMPA1. J Biol Chem. 2007 Jan 5;282(1):637-46. Epub 2006 Oct 26. [PubMed:17068342 ]
  4. Tanizawa Y, Kuhara A, Inada H, Kodama E, Mizuno T, Mori I: Inositol monophosphatase regulates localization of synaptic components and behavior in the mature nervous system of C. elegans. Genes Dev. 2006 Dec 1;20(23):3296-310. [PubMed:17158747 ]
  5. Ohnishi T, Yamada K, Ohba H, Iwayama Y, Toyota T, Hattori E, Inada T, Kunugi H, Tatsumi M, Ozaki N, Iwata N, Sakamoto K, Iijima Y, Iwata Y, Tsuchiya KJ, Sugihara G, Nanko S, Osumi N, Detera-Wadleigh SD, Kato T, Yoshikawa T: A promoter haplotype of the inositol monophosphatase 2 gene (IMPA2) at 18p11.2 confers a possible risk for bipolar disorder by enhancing transcription. Neuropsychopharmacology. 2007 Aug;32(8):1727-37. Epub 2007 Jan 24. [PubMed:17251911 ]
General function:
Involved in inositol or phosphatidylinositol phosphatase activity
Specific function:
Can use myo-inositol monophosphates, scylloinositol 1,4-diphosphate, glucose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. Has been implicated as the pharmacological target for lithium Li(+) action in brain.
Gene Name:
IMPA2
Uniprot ID:
O14732
Molecular weight:
31320.525
References
  1. Cryns K, Shamir A, Shapiro J, Daneels G, Goris I, Van Craenendonck H, Straetemans R, Belmaker RH, Agam G, Moechars D, Steckler T: Lack of lithium-like behavioral and molecular effects in IMPA2 knockout mice. Neuropsychopharmacology. 2007 Apr;32(4):881-91. Epub 2006 Jul 12. [PubMed:16841073 ]
  2. Ohnishi T, Ohba H, Seo KC, Im J, Sato Y, Iwayama Y, Furuichi T, Chung SK, Yoshikawa T: Spatial expression patterns and biochemical properties distinguish a second myo-inositol monophosphatase IMPA2 from IMPA1. J Biol Chem. 2007 Jan 5;282(1):637-46. Epub 2006 Oct 26. [PubMed:17068342 ]
  3. Ohnishi T, Yamada K, Ohba H, Iwayama Y, Toyota T, Hattori E, Inada T, Kunugi H, Tatsumi M, Ozaki N, Iwata N, Sakamoto K, Iijima Y, Iwata Y, Tsuchiya KJ, Sugihara G, Nanko S, Osumi N, Detera-Wadleigh SD, Kato T, Yoshikawa T: A promoter haplotype of the inositol monophosphatase 2 gene (IMPA2) at 18p11.2 confers a possible risk for bipolar disorder by enhancing transcription. Neuropsychopharmacology. 2007 Aug;32(8):1727-37. Epub 2007 Jan 24. [PubMed:17251911 ]
General function:
Involved in protein kinase activity
Specific function:
Participates in the Wnt signaling pathway. Implicated in the hormonal control of several regulatory proteins including glycogen synthase, MYB and the transcription factor JUN. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates MUC1 in breast cancer cells, and decreases the interaction of MUC1 with CTNNB1/beta-catenin. Phosphorylates CTNNB1/beta-catenin. Phosphorylates SNAI1
Gene Name:
GSK3B
Uniprot ID:
P49841
Molecular weight:
46743.9
References
  1. Borsotto M, Cavarec L, Bouillot M, Romey G, Macciardi F, Delaye A, Nasroune M, Bastucci M, Sambucy JL, Luan JJ, Charpagne A, Jouet V, Leger R, Lazdunski M, Cohen D, Chumakov I: PP2A-Bgamma subunit and KCNQ2 K+ channels in bipolar disorder. Pharmacogenomics J. 2007 Apr;7(2):123-32. Epub 2006 May 30. [PubMed:16733521 ]
  2. Adli M, Hollinde DL, Stamm T, Wiethoff K, Tsahuridu M, Kirchheiner J, Heinz A, Bauer M: Response to lithium augmentation in depression is associated with the glycogen synthase kinase 3-beta -50T/C single nucleotide polymorphism. Biol Psychiatry. 2007 Dec 1;62(11):1295-302. Epub 2007 Jul 12. [PubMed:17628506 ]
  3. O'Brien WT, Klein PS: Validating GSK3 as an in vivo target of lithium action. Biochem Soc Trans. 2009 Oct;37(Pt 5):1133-8. doi: 10.1042/BST0371133. [PubMed:19754466 ]
General function:
Involved in binding
Specific function:
Involved in signal transduction through the Wnt pathway. Nuclear beta-catenin it involved in transcriptional regulation by association with transcription factors of the TCF/LEF family
Gene Name:
CTNNB1
Uniprot ID:
P35222
Molecular weight:
85495.9
General function:
Amino acid transport and metabolism
Specific function:
Functions as a sodium-dependent amino acid transporter. Mediates the saturable, pH-sensitive and electrogenic cotransport of glutamine and sodium ions with a stoichiometry of 1:1. May also transport small zwitterionic and aliphatic amino acids with a lower affinity. May supply glutamatergic and GABAergic neurons with glutamine which is required for the synthesis of the neurotransmitters glutamate and GABA
Gene Name:
SLC38A1
Uniprot ID:
Q9H2H9
Molecular weight:
54047.0
General function:
Involved in transmembrane transport
Specific function:
Transports Ca(2+) in exchange for either Li(+) or Na(+), explaining how Li(+) catalyzes Ca(2+) exchange. In contrast to other members of the family its function is independent of K(+)
Gene Name:
SLC24A6
Uniprot ID:
Q6J4K2
Molecular weight:
64230.8