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Bovine Rumen Metabolome Database



Showing metabocard for Lithium (RMDB05949)

Legend: metabolite field enzyme field

Version 1.0
Creation Date 2007-04-12 19:30:36
Update Date 2009-03-27 15:55:13
Accession Number RMDB05949
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)
Synonyms
  1. Li
  2. Lithium atom
  3. Lithium element
  4. Li(+) ion
  5. Li(+) cation
Chemical IUPAC Name lithium
Chemical Formula [Li]+
Chemical Structure Structure
Chemical Taxonomy
Kingdom
  • Inorganic
Super Class
  • Inorganic compounds
Class
  • Inorganic Ions and Gases
Sub Class
  • Metals
Family
  • Mammalian_Metabolite
Species
Biofunction
  • Osmolyte, enzyme cofactor, signalling
Application
Source
  • Endogenous
Average Molecular Weight 6.941
Monoisotopic Molecular Weight 7.016000
Isomeric SMILES [Li+]
Canonical SMILES [Li+]
KEGG Compound ID C15473 Link Image
BioCyc ID LI%2b Link Image
BiGG ID Not Available
Wikipedia Link Not Available
METLIN ID Not Available
PubChem Compound 28486 Link Image
PubChem Substance 47204991 Link Image
ChEBI ID 30145 Link Image
CAS Registry Number 7439-93-2
InChI Identifier InChI=1/Li/q+1
Synthesis Reference Not Available
Melting Point (Experimental) 190 oC
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility Not Available Calculated using ALOGPS
Physiological Charge 1
State Solid
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP/Hydrophobicity Not Available Calculated using ALOGPS
Material Safety Data Sheet (MSDS)
MOL File Show Link Image
SDF File Show Link Image
PDB File Show Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Experimental 1H NMR Spectrum Not Available
Experimental 13C NMR Spectrum Not Available
Experimental 13C HSQC Spectrum Not Available
Predicted 1H NMR Spectrum Not Available
Not Available
Predicted 13C NMR Spectrum Not Available
Not Available
Mass Spectrum Not Available
Simplified TOCSY Spectrum Not Available
BMRB Spectrum Not Available
Cellular Location Not Available
Biofluid Location
  • Rumen
Tissue Location Not Available
Concentrations (Normal)
Biofluid Rumen
Value 3.898+/- 0.5 uM
Age N/A
Sex Female
Condition Normal
Breed Not Available
Experimental Condition Not Available
Comments Not Available
References
  • The rumen metabolome (in preparation)
Concentrations (Abnormal) Not Available
Pathway Names Not Available
HMDB Pathways Not Available
KEGG Pathways Not Available
SimCell Pathways Not Available
General References Not Available
Metabolic Enzymes
  1. 3'(2'),5'-bisphosphate nucleotidase 1
  2. Inositol monophosphatase
  3. Inositol polyphosphate 1-phosphatase
Enzyme 1 [top]
Enzyme 1 ID 195
Enzyme 1 Name 3'(2'),5'-bisphosphate nucleotidase 1
Enzyme 1 Synonyms
  1. Bisphosphate 3'-nucleotidase 1
Enzyme 1 Gene Name BPNT1
Enzyme 1 Protein Sequence >3'(2'),5'-bisphosphate nucleotidase 1
MASSPTVLMRLVASAYSIAQKAGTIVRRVIAEGDLGIIEKTCATDLQTKADRLVQVSICS
SLARKFPKLTIIGEEDLPPEDVDQELIEDGQWEEILKQPCPSQYSAIKEEDLVVWVDPLD
GTKEYTEGLLDNVTVLIGIAYEGKAIAGVINQPYYNYQAGPDAVLGRTIWGVLGLGAFGF
QLKEAPAGKHIITTTRSHNSQLVTDCITAMNPDDVLRVGGAGNKIIQLIEGKASAYVFAS
PGCKKWDTCAPEVILHAVGGKLTDIHGNALQYNKEVKHMNSAGVLATLRNYDYYASRVPQ
SVKNALVP
Enzyme 1 Number of Residues 308
Enzyme 1 Molecular Weight 33327.9
Enzyme 1 Theoretical pI 5.19
Enzyme 1 GO Classification
Function
Process
Component
Enzyme 1 General Function Carbohydrate transport and metabolism
Enzyme 1 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
Enzyme 1 Pathways Not Available
Enzyme 1 Reactions Not Available
Enzyme 1 Pfam Domain Function
Enzyme 1 Signals
  • None
Enzyme 1 Transmembrane Regions
  • None
Enzyme 1 Essentiality Not Available
Enzyme 1 GenBank ID Protein 152941250 Link Image
Enzyme 1 UniProtKB/Swiss-Prot ID Q3ZCK3 Link Image
Enzyme 1 UniProtKB/Swiss-Prot Entry Name BPNT1_BOVIN Link Image
Enzyme 1 PDB ID 1JP4 Link Image
Enzyme 1 PDB File Show
Enzyme 1 3D Structure
Enzyme 1 Cellular Location Not Available
Enzyme 1 Gene Sequence >927 bp
ATGGCATCCAGTCCCACTGTGTTGATGCGGTTGGTGGCTTCAGCATATTCTATTGCTCAA
AAGGCAGGAACGATAGTCAGGCGTGTTATCGCCGAAGGAGACCTGGGTATCATTGAGAAG
ACCTGTGCAACAGACCTGCAGACCAAGGCTGACCGATTAGTTCAAGTGAGCATATGTTCT
TCATTGGCACGGAAGTTCCCCAAACTAACAATTATAGGGGAAGAGGATCTGCCTCCTGAA
GACGTGGATCAAGAGCTGATTGAAGATGGTCAGTGGGAGGAGATACTGAAGCAGCCGTGC
CCATCACAGTACAGTGCTATCAAGGAGGAAGATCTTGTGGTCTGGGTTGATCCTCTGGAT
GGGACCAAGGAATATACTGAAGGTCTTCTTGACAATGTAACAGTACTTATTGGAATTGCT
TATGAAGGAAAAGCCATAGCAGGAGTTATTAACCAGCCATATTACAACTACCAGGCAGGA
CCAGATGCTGTGCTGGGGAGAACTATCTGGGGAGTTTTGGGTTTAGGTGCCTTCGGGTTT
CAGCTGAAAGAAGCGCCCGCCGGCAAACACATCATCACAACAACCCGGTCCCATAACAGC
CAGTTGGTTACGGACTGCATCACTGCTATGAACCCTGATGATGTGCTGAGAGTGGGAGGA
GCAGGAAATAAGATAATTCAGCTGATTGAAGGCAAAGCCTCTGCTTATGTATTTGCAAGT
CCAGGATGCAAGAAGTGGGACACCTGTGCTCCAGAAGTCATTTTACATGCTGTCGGAGGC
AAGTTAACCGATATCCATGGAAATGCTCTTCAGTATAACAAGGAAGTGAAGCACATGAAC
TCGGCCGGAGTCCTGGCCACACTGAGGAATTATGACTATTATGCAAGTCGAGTCCCCCAG
TCTGTTAAAAATGCCCTTGTTCCTTGA
Enzyme 1 GenBank Gene ID BT030746 Link Image
Enzyme 1 GeneCard ID BPNT1 Link Image
Enzyme 1 GenAtlas ID Not Available
Enzyme 1 HGNC ID Not Available
Enzyme 1 Chromosome Location Chromosome:1
Enzyme 1 Locus 1q41
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 General References
  1. [PubMed Link Image]
Enzyme 1 Metabolite References Not Available
Enzyme 2 [top]
Enzyme 2 ID 456
Enzyme 2 Name Inositol monophosphatase
Enzyme 2 Synonyms
  1. Inositol-1(or 4)-monophosphatase
  2. IMPase
  3. IMP
  4. Lithium-sensitive myo-inositol monophosphatase A1
Enzyme 2 Gene Name IMPA1
Enzyme 2 Protein Sequence >Inositol monophosphatase
MADPWQECMDYAVTLAGQAGEVVREALKNEMNIMVKSSPADLVTATDQKVEKMLITSIKE
KYPSHSFIGEESVAAGEKSILTDNPTWIIDPIDGTTNFVHGFPFVAVSIGFVVNKKMEFG
IVYSCLEDKMYTGRKGKGAFCNGQKLQVSHQEDITKSLLVTELGSSRTPETVRIILSNIE
RLLCLPIHGIRGVGTAALNMCLVAAGAADAYYEMGIHCWDVAGAGIIVTEAGGVLLDVTG
GPFDLMSRRVIASSNKTLAERIAKEIQIIPLQRDDED
Enzyme 2 Number of Residues 277
Enzyme 2 Molecular Weight 30055.3
Enzyme 2 Theoretical pI 4.81
Enzyme 2 GO Classification
Function
Process
Component
Enzyme 2 General Function Carbohydrate transport and metabolism
Enzyme 2 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
Enzyme 2 Pathways
  • Polyol metabolism
  • myo-inositol biosynthesis
  • myo- inositol from D-glucose 6-phosphate:step 2/2
Enzyme 2 Reactions Not Available
Enzyme 2 Pfam Domain Function
Enzyme 2 Signals
  • None
Enzyme 2 Transmembrane Regions
  • None
Enzyme 2 Essentiality Not Available
Enzyme 2 GenBank ID Protein 163225 Link Image
Enzyme 2 UniProtKB/Swiss-Prot ID P20456 Link Image
Enzyme 2 UniProtKB/Swiss-Prot Entry Name IMPA1_BOVIN Link Image
Enzyme 2 PDB ID 2BJI Link Image
Enzyme 2 PDB File Show
Enzyme 2 3D Structure
Enzyme 2 Cellular Location Not Available
Enzyme 2 Gene Sequence >834 bp
ATGGCTGATCCTTGGCAGGAATGCATGGATTATGCAGTAACCCTGGCAGGACAAGCTGGA
GAGGTGGTTCGTGAAGCGCTCAAGAATGAAATGAATATTATGGTTAAAAGTTCTCCGGCT
GATTTGGTAACTGCTACTGACCAAAAAGTTGAAAAAATGCTTATCACATCCATAAAGGAA
AAGTATCCATCTCACAGTTTCATTGGTGAGGAATCTGTGGCAGCTGGGGAAAAAAGTATC
TTAACCGACAACCCTACATGGATCATTGACCCTATTGATGGAACAACTAACTTTGTACAT
GGATTTCCTTTTGTAGCTGTTTCAATTGGCTTTGTGGTAAATAAAAAGATGGAGTTTGGA
ATTGTGTACAGTTGCCTGGAGGATAAGATGTACACTGGCCGGAAAGGAAAAGGTGCCTTT
TGTAATGGTCAAAAACTACAGGTTTCACACCAAGAAGATATTACCAAATCTCTCTTGGTG
ACAGAGTTGGGCTCTTCCAGAACACCAGAGACTGTGAGAATTATTCTTTCTAATATAGAA
AGGCTTCTTTGCCTTCCCATCCATGGGATCCGGGGTGTTGGAACAGCAGCTCTGAACATG
TGCCTGGTGGCCGCTGGGGCTGCGGACGCGTATTATGAAATGGGGATCCACTGCTGGGAT
GTTGCAGGCGCCGGCATCATTGTGACTGAAGCTGGCGGAGTGCTCCTGGATGTCACAGGT
GGACCATTTGATTTGATGTCACGAAGAGTAATTGCTTCAAGCAATAAAACATTAGCAGAA
AGGATAGCCAAAGAAATTCAGATAATACCTCTTCAAAGAGATGATGAAGATTAA
Enzyme 2 GenBank Gene ID J05394 Link Image
Enzyme 2 GeneCard ID IMPA1 Link Image
Enzyme 2 GenAtlas ID Not Available
Enzyme 2 HGNC ID Not Available
Enzyme 2 Chromosome Location Chromosome:8
Enzyme 2 Locus 8q21.13-q21.3
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 General References
  1. [PubMed Link Image]
Enzyme 2 Metabolite References Not Available
Enzyme 3 [top]
Enzyme 3 ID 461
Enzyme 3 Name Inositol polyphosphate 1-phosphatase
Enzyme 3 Synonyms
  1. IPPase
  2. IPP
Enzyme 3 Gene Name INPP1
Enzyme 3 Protein Sequence >Inositol polyphosphate 1-phosphatase
MSDILQELLRVSEKAANIARACRQQETLFQLLIEEKKEGEKNKKFAVDFKTLADVLVQEV
IKENMENKFPGLGKKIFGEESNEFTNDLGEKIIMRLGPTEEETVALLSKVLNGNKLASEA
LAKVVHQDVFFSDPALDSVEINIPQDILGIWVDPIDSTYQYIKGSADITPNQGIFPSGLQ
CVTVLIGVYDIQTGVPLMGVINQPFVSQDLHTRRWKGQCYWGLSYLGTNIHSLLPPVSTR
SNSEAQSQGTQNPSSEGSCRFSVVISTSEKETIKGALSHVCGERIFRAAGAGYKSLCVIL
GLADIYIFSEDTTFKWDSCAAHAILRAMGGGMVDLKECLERNPDTGLDLPQLVYHVGNEG
AAGVDQWANKGGLIAYRSEKQLETFLSRLLQHLAPVATHT
Enzyme 3 Number of Residues 400
Enzyme 3 Molecular Weight 43964.8
Enzyme 3 Theoretical pI 5.06
Enzyme 3 GO Classification
Function
Process
Component
Enzyme 3 General Function Inorganic ion transport and metabolism
Enzyme 3 Specific Function 1D-myo-inositol 1,4-bisphosphate + H(2)O = 1D- myo-inositol 4-phosphate + phosphate
Enzyme 3 Pathways
  • Signal transduction
  • phosphatidylinositol signaling pathway
Enzyme 3 Reactions Not Available
Enzyme 3 Pfam Domain Function
Enzyme 3 Signals
  • None
Enzyme 3 Transmembrane Regions
  • None
Enzyme 3 Essentiality Not Available
Enzyme 3 GenBank ID Protein 163223 Link Image
Enzyme 3 UniProtKB/Swiss-Prot ID P21327 Link Image
Enzyme 3 UniProtKB/Swiss-Prot Entry Name INPP_BOVIN Link Image
Enzyme 3 PDB ID 1INP Link Image
Enzyme 3 PDB File Show
Enzyme 3 3D Structure
Enzyme 3 Cellular Location Not Available
Enzyme 3 Gene Sequence >1203 bp
ATGTCAGATATCCTCCAAGAGCTGCTCCGAGTCTCTGAGAAAGCTGCCAACATTGCCCGG
GCGTGCAGGCAGCAGGAAACCCTCTTCCAGCTGCTGATAGAAGAAAAGAAAGAGGGAGAA
AAGAACAAGAAGTTTGCAGTTGATTTCAAGACCCTGGCTGATGTACTGGTACAGGAAGTT
ATCAAAGAGAATATGGAGAACAAGTTTCCAGGCTTGGGGAAAAAAATTTTTGGAGAAGAA
TCCAATGAACTTACTAATGATTTGGGGGAAAAGATTATCATGAGACTGGGTCCTACAGAG
GAAGAAACAGTAGCTCTTCTCAGCAAAGTCCTTAATGGTAACAAGCTGGCATCTGAGGCC
TTAGCCAAGGTTGTGCACCAGGACGTTTTCTTCAGTGACCCAGCTCTGGATTCAGTAGAG
ATCAACATTCCACAGGACATCTTGGGAATCTGGGTGGATCCTATAGATTCAACTTACCAG
TATATAAAAGGTTCTGCTGACATTACACCCAACCAAGGAATCTTCCCCAGTGGACTTCAG
TGCGTCACTGTTTTGATTGGTGTCTATGACATACAGACAGGGGTGCCTCTCATGGGAGTC
ATCAACCAACCTTTTGTATCACAAGACCTACACACCCGCAGGTGGAAAGGACAGTGCTAC
TGGGGCCTTTCTTACCTGGGGACCAATATCCATTCCCTTCTGCCTCCTGTCTCTACAAGA
AGCAACAGCGAAGCGCAGAGCCAAGGGACCCAAAACCCCAGCTCCGAAGGCTCCTGCCGG
TTCTCAGTGGTCATTAGTACCAGTGAAAAGGAGACCATCAAGGGCGCGTTGTCGCATGTG
TGTGGAGAGCGCATCTTCCGGGCAGCTGGGGCTGGTTACAAGAGCCTCTGTGTGATCCTC
GGCCTCGCTGACATTTACATCTTCTCAGAAGATACCACGTTCAAGTGGGACTCCTGTGCT
GCCCACGCCATCCTCAGGGCCATGGGTGGGGGCATGGTGGACTTAAAAGAATGCCTGGAA
AGAAATCCTGACACGGGCCTTGACTTGCCACAGCTGGTGTATCACGTGGGAAACGAAGGC
GCTGCTGGAGTAGATCAGTGGGCCAACAAGGGAGGACTCATCGCATACAGATCAGAGAAG
CAGCTGGAGACGTTCTTGAGCCGCCTCCTCCAGCACCTTGCCCCTGTGGCTACACACACG
TAG
Enzyme 3 GenBank Gene ID M55916 Link Image
Enzyme 3 GeneCard ID INPP1 Link Image
Enzyme 3 GenAtlas ID Not Available
Enzyme 3 HGNC ID Not Available
Enzyme 3 Chromosome Location Chromosome:2
Enzyme 3 Locus 2q32
Enzyme 3 SNPs SNPJam Report Link Image
Enzyme 3 General References
  1. [PubMed Link Image]
Enzyme 3 Metabolite References Not Available