Nonenzymatic glycosylation of human hemoglobin at multiple sites

Abstract

The most abundant minor hemoglobin component of human hemolysate is Hb A 1c, which has glucose bound to the N-terminus of the β chain by a ketoamine linkage. Hb A 1c is formed slowly and continuously throughout the 120 day lifespan of the red cell. It can be synthesized in vitro by incubating purified hemoglobin with 14C-glucose. Other minor components, Hb A 1a1 and Hb A 1a2 are adducts of sugar phosphates at the N-terminus of the β chain. Hb A 1b contains an unidentified nonphosphorylated sugar at the β N-terminus. In addition, a significant portion of the major hemoglobin component (Hb A 0) is also glycosylated by a glucose ketoamine linkage at other sites on the molecule, including the N-terminus of the α chain and the ϵ-amino group of several lysine residues on both the α and the β chains. The results indicate that the interaction of glucose and hemoglobin is rather nonspecific and suggests that other proteins are modified in a similar fashion.