| 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  , 17316163 , 8110911 , 17288494 ). |
| Structure |
Download:
MOL |
SDF |
SMILES |
InChI
Display:
2D Structure |
3D Structure
|
| Synonyms |
- Li
- Li(+) cation
- Li(+) ion
- Lithium atom
- 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 |
|
| Direct Parent |
Homogeneous Alkali Metal Compounds |
| Ontology |
|---|
| Status |
Detected and Quantified |
| Origin |
|
| Biofunction |
- Osmolyte, enzyme cofactor, signalling
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| 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 |
|
| Spectra |
|---|
|
Not Available
|
| Biological Properties |
|---|
| Cellular Locations |
Not Available
|
| Biofluid Locations |
- Blood
- Cerebrospinal Fluid (CSF)
- Urine
|
| Tissue Location |
Not Available
|
| Pathways |
Not Available
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| Normal Concentrations |
|---|
|
| 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 |
Normal
|
|
| Urine |
Detected and Quantified |
|
0.504 (0.058-3.414) umol/mmol creatinine |
Adult (>18 years old) |
Not Specified |
Normal
|
|
|
| Abnormal Concentrations |
|---|
|
| 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
|
| 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
|
| 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
|
|
| Associated OMIM IDs |
|
| External Links |
|---|
| DrugBank ID |
DB01356 |
| 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 |
| KEGG Compound ID |
C15473 |
| BioCyc ID |
LI%2b |
| BiGG ID |
Not Available |
| Wikipedia Link |
Not Available |
| NuGOwiki Link |
HMDB05949 |
| Metagene Link |
HMDB05949 |
| METLIN ID |
Not Available |
| PubChem Compound |
28486 |
| PDB ID |
LI |
| ChEBI ID |
49713 |
| References |
|---|
| Synthesis Reference |
Not Available |
| Material Safety Data Sheet (MSDS) |
Download (PDF)
|
| General References |
- Zhong J, Lee WH: Lithium: a novel treatment for Alzheimer's disease? Expert Opin Drug Saf. 2007 Jul;6(4):375-83.
Pubmed: 17688381
- 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
- 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
- Waring WS: Management of lithium toxicity. Toxicol Rev. 2006;25(4):221-30.
Pubmed: 17288494
|
Normal
