The inositol trisphosphate phosphomonoesterase of the human erythrocyte membrane

On the basis of its substrate specificity and the inhibition by 2,3-bisphosphoglycerate, we suggest that this enzyme is selective for the 5-phosphate in those water-soluble phosphate esters of inositol that possess the vicinal pair of 4,5-phosphates but that it may interact less strongly with other water-soluble compounds that have pairs of vicinal phosphates

C P Downes; M C Mussat; R H Michell

2015

Scholarcy highlights

  • Three inositol phospholipids, namely phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate appear likely to be constituents of all eukaryote cells
  • In the presence of Mg2+, the released Ins(1,4,L-myoinositol 1 was further degraded to a compound that eluted with Ins(1,4)P2, and this appeared to be relatively stable in the presence of erythrocyte membranes and Mg2+
  • We previously showed that human erythrocyte membranes display phosphomonoesterase activity towards Ins(1,4,5)P3, and the results presented here demonstrate that such membranes possess an Mg2+-dependent phosphomonoesterase that selectively attacks only the 5-phosphate of Ins(1,4,5)P3 and of glycerophosphoinositol 4,5-bisphosphate
  • Inhibition by 2,3-bisphosphoglycerate suggested that the enzyme has a particular affinity for pairs of vicinal monoester phosphates, and raised the possibility that we might have been observing degradation of Ins(1,4,5)P3 by the previously described 2,3-bisphosphoglycerate phosphomonoesterase activity of the erythrocyte; this activity represents a composite of the reversal of 2,3-bisphosphoglycerate synthase and a sidereaction catalysed by 2,3-bisphosphoglycerate mutase
  • Bisphosphoglycerate of this composite activity is close to the K, for inhibition of Ins( 1,4,5)P3 breakdown by 2,3-bisphosphoglycerate
  • Ins(1,4,5)P3 phosphomonoesterase that we studied was tightly bound to the membrane, persisting in an isoionic ghost preparation and in low-ionic-strength ghosts that were washed with iso-osmotic saline; 2,3-bisphosphoglycerate phosphomonoesterase activity is mainly cytosolic
  • The water-soluble phosphate ester produced by treatment of Ptdlns(4,5)P2 with mild alkali, opens up the possibility of using sequential attack on glycerophosphoinositol 4,5-bisphosphate, first by Ins(1,4,L-myoinositol 1 phosphatase to remove the 5-phosphate and by an unspecific phosphatase to remove the 4-phosphate, to analyse the detailed metabolism of each of these three phosphates in PtdIns(4,5)P2

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