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MOLECULAR EFFECTS of lithium
Table 1.
Direct Targets of Lithium
| Enzyme | Function |
|---|---|
| Reproduced with permission from Gould et al., Mol. Psychiatry (2004) | |
| Inositol monophosphatase (IMPase) | Rate limiting enzyme in inositol recycling; lithium’s inhibition of IMPase led to the inositol depletion hypothesis of lithium’s actions |
| Inositol polyphosphate 1-phosphatase (IPPase) | Enzyme involved in inositol recylcing in phosphoinositol signaling; acts prior to IMPase |
| Bisphosphate nucleotidase (BPNase) | Removes phosphate from 3′-phosphoadenosine 5′-phosphate (PAP) to form adenosine 5′phosphate (AMP); an increase in PAP inhibits sulphotransferases, which transfer sulfur to biological molecules |
| Fructose 1,6-bisphosphastase (FBPase) | Key enzyme in glyconeogenesis; catalyzes the removal of the 1-phosphate from fructose 1, 6-bisphosphatase to form fructose 6-phosphate |
| Phosphoglucomutase (PGM) | Key enzyme in glycogenolysis and glycogenesis; catalyzes the formation of glucose 1-phosphate from glucose 6-phosphate during glycogenolysis (and the reverse during glycogenesis) |
| Glycogen synthase kinase-3 (GSK-3) | Normally active kinase that is inhibited by the activity of many signaling pathways; inhibiting GSK-3 has been linked to neurotrophic support, neuroprotection, and possible modulation of circadian rhythms |
