Antioxidant functions of Inositol 1,2,3-trisphosphate and Inositol 1,2,3,6-tetrakisphosphate

Abstract Iron chelates of inositol 1,2,3-trisphosphate and inositol 1,2,3,6-tetrakisphosphate lacked free coordination sites and prevented the iron-catalyzed oxidation of ascorbic acid and peroxidation of arachidonic acid. In contrast, iron chelates of inositol 1,2,6-trisphosphate and inositol 1,2,5,6-tetrakisphosphate contained available coordination sites, permitted iron-catalyzed ascorbic acid oxidation, and enhanced arachidonic acid peroxidation. It was concluded that the 1,2,3-trisphosphate grouping of inositol hexakisphosphate was responsible for the inhibition of iron-catalyzed hydroxyl radical formation. The structure of the chelate with the phosphates in an axial-equatorial-axial configuration appeared to be the only possible inositol trisphosphate that could form bonds between six oxygen atoms and the six coordination sites on iron. K m values for cleavage by Escherichia coli alkaline phosphatase were as follows: inositol 1,2,3-trisphosphate, 56 μ M; inositol 1,2,6-trisphosphate, 35 μ M; inositol 1,2,3,6-tetrakisphosphate, 139 μ M; and inositol 1,2,5,6-tetrakisphosphate, 100 μ M. The initial hydrolysis rates of 200 μ M solutions of the latter three isomers by E. coli alkaline phosphatase were not affected by an equimolar concentration of iron, whereas the rate for inositol 1,2,3-trisphosphate decreased in the presence of iron to 50% of the control. Therefore, the antioxidant potential of inositol 1,2,3-trisphosphate and inositol 1,2,3,6-tetrakisphosphate in cells and other biological systems may be fortified by the resistance of their iron chelates to enzymatic hydrolysis of the functional 1,2,3-trisphosphate array. Copyright © 1997 Elsevier Science Inc.