A novel target of lithium therapy

  title={A novel target of lithium therapy},
  author={Lynne Yenush and J M Bell{\'e}s and Jos{\'e} Miguel L{\'o}pez-Coronado and R Gil-Mascarell and Raquel Serrano and Pedro L. Rodriguez},
  journal={FEBS Letters},
Is phosphoadenosine phosphate phosphatase a target of lithium’s therapeutic effect?
The results question the relevance of PAP phosphatase to the therapeutic mechanism of lithium, and a statistically significant 25% reduced brain ADP/ATP ratio was found following lithium treatment in line with lithium’s suggested neuroprotective effects.
Possible role of 3′(2′)-phosphoadenosine-5′-phosphate phosphatase in the etiology and therapy of bipolar disorder
  • G. Agam, G. Shaltiel
  • Biology, Psychology
    Progress in Neuro-Psychopharmacology and Biological Psychiatry
  • 2003
3′-5′ Phosphoadenosine phosphate is an inhibitor of PARP-1 and a potential mediator of the lithium-dependent inhibition of PARP-1 in vivo
It is shown that pAp can interact with PARP-1 and inhibit its poly(ADP-ribosyl)ation activity and that upon treatment with lithium, a very potent inhibitor of the enzyme responsible for pAp recycling, HeLa cells exhibited a reduced level of poly(ADEp-ribose)ation in response to oxidative stress.
Oligoribonuclease is a common downstream target of lithium-induced pAp accumulation in Escherichia coli and human cells
It is demonstrated that Orn can degrade short DNA oligos in addition to its activity on RNA oligos, similar to what was documented for Sfn, and point to remarkable conservation of the connection between sulfur- and RNA metabolism between E.coli and humans.
Crystal structure of an enzyme displaying both inositol-polyphosphate-1-phosphatase and 3'-phosphoadenosine-5'-phosphate phosphatase activities: a novel target of lithium therapy.
RnPIP is potently inhibited by lithium and, as the accumulation of PAP inhibits a variety of proteins, including sulphotransferases and RNA processing enzymes, this dual specificity enzyme represents a potential target of lithium action, in addition to inositol monophosphatases.
Structural elucidation of a dual-activity PAP phosphatase-1 from Entamoeba histolytica capable of hydrolysing both 3'-phosphoadenosine 5'-phosphate and inositol 1,4-bisphosphate.
This enzyme appears to function using a mechanism involving three-metal-ion assisted catalysis, which indicates that the sensitivity to alkali-metal ions may depend on the orientation of a specific catalytic loop.
Molecular cloning and biochemical characterization of a 3′(2′),5′‐bisphosphate nucleotidase from Debaryomyces hansenii
Evidence is presented that Dhal2p displays significantly higher resistance towards lithium and sodium ions than other homologues from yeast, and the nucleotide sequence of DHAL2 gene has been submitted to Genbank.
A Plant 3′-Phosphoesterase Involved in the Repair of DNA Strand Breaks Generated by Oxidative Damage*
Two novel, structurally and functionally distinct phosphatases have been identified through the functional complementation, by maize cDNAs, of an Escherichia colidiphosphonucleoside phosphatase mutant strain, and ZmDP2 is the first DNA 3-phosphoesterase thus far identified in plants capable of converting 3′-blocked termini into priming sites for reparative DNA polymerization.
Structural and functional studies of enzymes in nucleotide metabolism
Two enzymes; uridine monophosphate kinase (UMPK) from Ureaplasma parvum (Up) and human phosphoribosyltransferase domain containing protein 1 (PRTFDC1), have been investigated and a nucleoside analog library (NAL) consisting of 45 FDA-approved nucleosid analogs has been developed.
Molecular targets of lithium action.
In this review, lithium sensitive enzymes are discussed, and a number of criteria are proposed to evaluate which of these enzymes are involved in the response to lithium in a given setting.


A Novel Mammalian Lithium-sensitive Enzyme with a Dual Enzymatic Activity, 3′-Phosphoadenosine 5′-Phosphate Phosphatase and Inositol-polyphosphate 1-Phosphatase*
It is proposed that the PAP phosphatase activity of RnPIP is crucial for the function of enzymes sensitive to inhibition by PAP, such as sulfotransferase and RNA processing enzymes.
Cloning and Characterization of a Mammalian Lithium-sensitive Bisphosphate 3′-Nucleotidase Inhibited by Inositol 1,4-Bisphosphate*
It is proposed that inhibition of human BPntase may account for lithium-induced nephrotoxicity, which may be overcome by supplementation of current therapeutic regimes with inhibitors of nucleotide biosynthesis, such as methionine.
Lithium toxicity in yeast is due to the inhibition of RNA processing enzymes
It is reported that pAp accumulation in HAL2 mutants inhibits the 5′→3′ exoribonucleases Xrn1p and Rat1p, and it is proposed that Li+ toxicity in yeast is due to synthetic lethality evoked between Xrn 1p and RNase MRP.
Definition of a metal-dependent/Li(+)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure.
These proteins define an ancient structurally conserved family involved in diverse metabolic pathways including inositol signaling, gluconeogenesis, sulfate assimilation, and possibly quinone metabolism and evolutionary comparison of the core sequences indicate that five distinct branches exist within this family.
The Yeast HAL2 Nucleotidase Is an in Vivo Target of Salt Toxicity*
The results suggest that the cation sensitivity of the HAL2 nucleotidase is an important determinant of the inhibition of yeast growth by sodium and lithium salts.
Partial Purification and Characterization of a 3'- Phosphoadenosine 5' -Phosphosulfate: Desulfoglucosinolate Sulfotransferase from Cress (Lepidium sativum).
The kinetics of desulfobenzylglucosinolate sulfation were consistent with a rapid equilibrium ordered mechanism with desulfolysis first and PAPS second, and all other potential substrates tested, including flavonoids, flavonoid glycosides, cinnamic acids, and phenylacetaldoxime, were not sulfated.
The Arabidopsis HAL2-like gene family includes a novel sodium-sensitive phosphatase.
AtAHL constitutes a novel type of sodium-sensitive PAP phosphatase which could act co-ordinately with plant sulphotransferases and serve as target of salt toxicity in plants.
A salt-sensitive 3'(2'),5'-bisphosphate nucleotidase involved in sulfate activation
Overexpression of a yeast gene, HAL2, allows the cells to tolerate higher than normal extracellular salt concentrations and offers routes by which genetic engineering can be used to improve the tolerance of various organisms to salt.