Naturally occurring chelators of Ca2+ and Mg2+ have largely been unrec
ognized due to their low binding affinities. They include carbohydrate
and cyclitol phosphates, nucleotides and nucleic acids. The calciotro
phic inositol phosphates Ins(1,4,5)P-3 and Ins(1,3,4,5)P-4 form chelat
es within the range of Ca2+ concentrations found in biological systems
. As well as being a likely source of experimental artifact where thes
e compounds have been investigated at unphysiological cation concentra
tions, chelation may have important physiological roles. The autoregul
ation of Ca2+ entry into the cell cytosol is one, whereas the coupling
of chelation with enzyme or receptor interactions offers a general me
chanism for divalent cation control of diverse biological processes. I
nositol monophosphate 1-phosphatase and inositol polyphosphate 1-phosp
hatase 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 i
on.