Inhibition of iron-catalysed hydroxyl radical formation by inositol polyphosphates: a possible physiological function for myo-inositol hexakisphosphate

• DOI: 10.1042/bj2940929
• Publication Date: 2015-08-10T21:34:24Z
• Authors: P T Hawkins; D R Poyner; T R Jackson; A J Letcher; D A Lander; R F Irvine
• Keywords: Inositol phosphate; Hydroxyl radical; Cyclitol

1. The ability of myo-inositol polyphosphates to inhibit iron-catalysed hydroxyl radical formation was studied in a hypoxanthine/xanthine oxidase system [Graf, Empson and Eaton (1987) J. Biol. Chem. 262, 11647-11650]. Fe3+ present the assay reagents supported some formation, standard assay, with 5 microM added, used investigate specificity compounds which could generation. 2. InsP6 (phytic acid) able this completely. In respect it similar effects high affinity chelator Desferral, dissimilar EDTA which, even at concentrations, still allowed detectable take place. 3. six isomers InsP5 were purified from an alkaline hydrolysate (four them as two enantiomeric mixtures), they compared assay. Ins(1,2,3,4,6)P5 D/L-Ins(1,2,3,4,5)P5 that caused complete inhibition > 30 microM. Ins(1,3,4,5,6)P5 D/L-Ins(1,2,4,5,6)P5, however, markedly less potent than InsP6, did not completely; when added up 600 microM, significant detected. Thus InsP5s lacking 2 or 1/3 phosphates are qualitatively different other InsP5s. 4. scyllo-Inositol hexakisphosphate also tested, although greater Ins(1,3,4,5,6)P5, too free 5. We conclude 1,2,3 (equatorial-axial-equatorial) phosphate grouping has conformation uniquely provides specific interaction iron totally its catalyse formation; we suggest physiological function might be act ‘safe’ binding site for during transport through cytosol cellular organelles.