COVALENT GLYCOINOSITOLPHOSPHOLIPID BINDING TO HEMOGLOBIN - A NEW POSTTRANSLATIONAL MODIFICATION OF HB OCCURRING IN HYPERINSULINISM WITH CONCOMITANT HYPOGLYCEMIA

In this work a novel hitherto unrecognised minor hemoglobin (Hb) fract ion, which we detected previously in hemolysates of erythrocytes expos ed to a high concentration of insulin under hypoglycemic conditions, b oth in vivo and in vitro, is analysed. The modification of Hb in HbA1x was shown to be due the addition of glycoinositolphospholipid (GPI) t o the C termini of both beta polypeptide chains. A structurally relate d minor Hb fraction was identified in erythrocytes exposed in vitro to insulin-mimetic agent, trypsin. To our knowledge this is the first de monstration of such a modification of Hb, as well as the first demonst ration of post-translational GPI binding to proteins in response to in sulin. The mechanism proposed for GPI-Hb formation is briefly describe d. (C) 1997 Academic Press.