Glycosylated hemoglobins are minor components of human red cell hemoglobin, Structurally, they are closely related to adult hemoglobin and are formed nonenzymatically by condensation of glucose or other reducing sugars with hemoglobin A. Biosynthesis, structure and function of these modified hemoglobin molecules as well as their clinical implications have been the subject of extensive investigations recently. Glycosylated hemoglobins, which are increased two-to three fold in the red cells of diabetic patients, are becoming an accepted quantitative indicator for assessing the control of diabetes mellitus. Possible correlations of glycosylated hemoglobins with secondary complications and sequelae of the disease are also being investigated. Although the major site of the linkage of the hexose molecule to hemoglobin is at N-terminus of the beta-chains, it has recently been proposed that glycosylation of both alpha and beta-chains can take place at multiple sites including at the N-terminus of alpha chain can take place at multiple sites including at the N-terminus of a alpha chain and epsilon-amino group of several lysine residues on both alpha and beta chains. Glycosylation of hemoglobin is a nonspecific, nonenzymatic, posttranslational protein modification and has been used as a model for similar modifications in other macromolecules such as plasma and lens crystalline proteins, and even insulin. This review considers current investigations on the biochemistry, biosynthesis and clinical implications of glycosylated hemoglobins and other proteins.
