Cellular actions of inositol phosphates and other natural calcium and magnesium chelators

Naturally occurring chelators of Ca2+ and Mg2+ have largely been unrecognized due to their low binding affinities. They include carbohydrate and cyclitol phosphates, nucleotides and nucleic acids. The calciotrophic inositol phosphates Ins(1,4,5)P3 and Ins(1,3,4,5)P4 form chelates within the range of Ca2+ concentrations found in biological systems. As well as being a likely source of experimental artifact where these compounds have been investigated at unphysiological cation concentrations, chelation may have important physiological roles. The autoregulation of Ca2+ entry into the cell cytosol is one, whereas the coupling of chelation with enzyme or receptor interactions offers a general mechanism for divalent cation control of diverse biological processes. Inositol monophosphate 1-phosphatase and inositol polyphosphate 1-phosphatase are two related enzymes which may conform to this mechanism. If so, it would provide a possible explanation for their sensitivity to divalent cations and for their non-competitive inhibition by lithium ion.