Modification of hemoglobin and other proteins by nonenzymatic glycosylation.

The most abundant minor hemoglobin component in human red cells is Hb AIc which is formed by the non-enzymatic condensation of glucose with the N-terminus of the beta-chain to form a stable ketoamine linkage. This adduct is increased in patients with diabetes mellitus and provides a useful index of diabetic control. In addition, glucose forms covalent attachments with lysine residues on both the alpha and beta chain, although these adducts are not readily separable by ordinary electrophoretic and chromatographic techniques. Additional minor hemoglobin components are formed by adducts with sugar phosphates. Nonenzymatic glycosylation also occurs on other proteins, particularly those with long turnover times and exposure to high concentrations of glucose. Examples include the proteins of the red cell membrane, albumin and lens crystallins. This phenomenon may be important in the pathogenesis of the long term control of diabetes.