Psychiatry related information on Impa1

• Lithium inhibits inositol monophosphatase at therapeutically effective concentrations, and it has been hypothesized that depletion of brain inositol levels is an important chemical alteration for lithium's therapeutic efficacy in bipolar disorder [1].

High impact information on Impa1

• The long-term effects of lithium are not caused by down-regulation of NMDA receptor subunit proteins and are unlikely related to its known ability to block inositol monophosphatase activity [2].
• The core fold of the enzyme is equivalent to that found in other Li(+)-sensitive phosphatases, such as inositol monophosphatase, but molecular modelling of I(1),(4)P(2) in the RnPIP active site reveals important structural determinants that accommodate this additional substrate [3].
• 8. When Li+ was present during stimulation, it redirected the dephosphorylation pathways downstream of Ins(1,4,5)P3 in the manner expected from its inhibition of inositol monophosphatase and Ins(1,4)P2/Ins(1,3,4)P3 1-phosphatase: there were marked increases in the accumulation of Ins(1,4)P2 and Ins(1,3,4)P3 and of monophosphates [4].
• Nucleoside diphosphatases [inosine diphosphatase (IDPase) and uridine diphosphatase (UDPase)] and nucleoside monophosphatases [uridine monophosphatase (UMPase) and inosine monophosphatase (IMPase)] were also determined [5].
• We conclude that rat liver cytosol contains an Ins(1,4)P2 1-phosphatase that is distinct from, but in many ways similar to, inositol monophosphatase [6].

Biological context of Impa1

• The substrate specificity of the purified enzyme agreed with that of inositol monophosphatase (EC 3.1.3.25) [7].
• IN nuclear import appears to be dependent on the Imp alpha/beta heterodimer and Ran GTP (Ran in its GTP-bound state), but does not require ATP [8].

Anatomical context of Impa1

• Both the qualitative and quantitative increases of IMPase 1 activity by chronic lithium treatment were substantiated by Western blot analysis of hippocampal and cerebral cortex regions [9].
• These results demonstrate that stimulatory effects of lithium on glucose transport are not mediated by the inhibition of IMPase and subsequent accumulation of IP1 in rat adipocytes [10].
• Under ether anesthesia a zirconium laminar implant was placed in the tibia following the method previously described by our laboratory (Cabrini et al Imp Dent 2:264-7, 1993) [11].

Associations of Impa1 with chemical compounds

• Although such effects may well be secondary to inhibition of inositol-monophosphatase, they are not reversed by inositol and therefore do not appear to result from depleted phosphoinositides [12].
• The applicability of the method is demonstrated by the in vivo monitoring of I(1)P levels in rat brain after administration of the inositol monophosphatase inhibitor lithium and the cholinergic agonist pilocarpine [13].
• Inositol monophosphatase (IMPase) inhibition is a hypothesized mechanism of action of lithium (Li) [14].
• The increased enzyme activity may alter critical neurochemical processes involving either free myo-inositol, the precursor of inositol based signaling system or other metabolic pathways, since IMPase 1 also utilizes selective sugar phosphates, such as galactose-1-phosphate, as substrates [9].
• Lithium inhibits the enzyme inositol monophosphatase and thus obstructs the enzymatic degradation of inositol triphosphate (IP3) to inositol in the phosphate-phosphoinositide (PIP) cycle [15].

Analytical, diagnostic and therapeutic context of Impa1

• Using a range of quantitative binding assays including enzyme-linked immunosorbent assay, fluorescence polarization, and native gel mobility electrophoresis, we assess the binding of importins to SRY, demonstrating a high affinity recognition (in the low nm range) by Imp beta independent of Imp alpha [16].
• The Ins(1,4)P2 1-phosphatase and inositol monophosphatase activities all share an apparent Mr of 47 x 10(3), as determined by gel-filtration chromatography [6].

References