Human Metabolome Database Version 3.5

Showing metabocard for Lithium (HMDB05949)

Record Information
Version 3.5
Creation Date 2007-04-12 12:30:36 -0600
Update Date 2013-05-29 13:42:26 -0600
HMDB ID HMDB05949
Secondary Accession Numbers None
Metabolite Identification
Common Name Lithium
Description Lithium (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 Link_out, 17316163 Link_out, 8110911 Link_out, 17288494 Link_out).
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  1. Li
  2. Li(+) cation
  3. Li(+) ion
  4. Lithium atom
  5. Lithium element
Chemical Formula Li
Average Molecular Weight 6.941
Monoisotopic Molecular Weight 7.016004049
IUPAC Name lithium(1+) ion
Traditional IUPAC Name lithium
CAS Registry Number 7439-93-2
SMILES [Li+]
InChI Identifier InChI=1S/Li/q+1
InChI Key HBBGRARXTFLTSG-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Inorganic Compounds
Super Class Homogeneous Metal Compounds
Class Homogeneous Alkali Metal Compounds
Sub Class N/A
Other Descriptors
  • a cation(Cyc)
  • alkali metal cation(ChEBI)
  • monoatomic monocation(ChEBI)
  • monovalent inorganic cation(ChEBI)
Substituents
  • N/A
Direct Parent Homogeneous Alkali Metal Compounds
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction
  • Osmolyte, enzyme cofactor, signalling
Application Not Available
Cellular locations Not Available
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 190 °C Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
LogP 0 ChemAxon
Hydrogen Acceptor Count 0 ChemAxon
Hydrogen Donor Count 0 ChemAxon
Polar Surface Area 0 A2 ChemAxon
Rotatable Bond Count 0 ChemAxon
Refractivity 0 ChemAxon
Polarizability 1.78 ChemAxon
Formal Charge 1 ChemAxon
Physiological Charge 1 ChemAxon
Spectra
Not Available
Biological Properties
Cellular Locations Not Available
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location Not Available
Pathways Not Available
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
0.14 +/- 0.10 uM Adult (>18 years old) Both Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
10.383 +/- 4.679 uM Adult (>18 years old) Not Specified Normal
Urine Detected and Quantified
0.5 (0.2-0.9) umol/mmol creatinine Adult (>18 years old) Both Comment Normal
Urine Detected and Quantified
0.504 (0.058-3.414) umol/mmol creatinine Adult (>18 years old) Not Specified Normal
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified 0.12 +/- 0.05 uM Adult (>18 years old) Both Multiple sclerosis
Blood Detected and Quantified 0.11 +/- 0.085 uM Adult (>18 years old) Both Parkinson's disease
Blood Detected and Quantified 0.16 +/- 0.074 uM Elderly (>65 years old) Both Alzheimer's disease
Associated Disorders and Diseases
Disease References
Alzheimer's disease
  • 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 Link_out
      Multiple sclerosis
      • 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 Link_out
          Parkinson's disease
          • 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 Link_out
              Associated OMIM IDs
              DrugBank ID DB01356 Link_out
              DrugBank Metabolite ID Not Available
              Phenol Explorer Compound ID Not Available
              Phenol Explorer Metabolite ID Not Available
              FoodDB ID FDB004181
              KNApSAcK ID Not Available
              Chemspider ID 26502 Link_out
              KEGG Compound ID C15473 Link_out
              BioCyc ID LI%2b Link_out
              BiGG ID Not Available
              Wikipedia Link Not Available
              NuGOwiki Link HMDB05949 Link_out
              Metagene Link HMDB05949 Link_out
              METLIN ID Not Available
              PubChem Compound 28486 Link_out
              PDB ID LI Link_out
              ChEBI ID 49713 Link_out
              References
              Synthesis Reference Not 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 Link_out
              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 Link_out
              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 Link_out
              4. Waring WS: Management of lithium toxicity. Toxicol Rev. 2006;25(4):221-30. Pubmed: 17288494 Link_out
              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 Link_out

              Enzymes
              Name: 3'(2'),5'-bisphosphate nucleotidase 1
              Reactions: Not Available
              Gene Name: BPNT1
              Uniprot ID: O95861 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Inositol polyphosphate 1-phosphatase
              Reactions: Not Available
              Gene Name: INPP1
              Uniprot ID: P49441 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Inositol monophosphatase 1
              Reactions: Not Available
              Gene Name: IMPA1
              Uniprot ID: P29218 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Inositol monophosphatase 2
              Reactions: Not Available
              Gene Name: IMPA2
              Uniprot ID: O14732 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Glycogen synthase kinase-3 beta
              Reactions: Not Available
              Gene Name: GSK3B
              Uniprot ID: P49841 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Catenin beta-1
              Reactions: Not Available
              Gene Name: CTNNB1
              Uniprot ID: P35222 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Sodium-coupled neutral amino acid transporter 1
              Reactions: Not Available
              Gene Name: SLC38A1
              Uniprot ID: Q9H2H9 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Sodium/potassium/calcium exchanger 6
              Reactions: Not Available
              Gene Name: SLC24A6
              Uniprot ID: Q6J4K2 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA