Chapter 25 Non-enzymatic Glycosylation

Abstract

This chapter summarizes the glycosylation of proteins by nonenzymatic processes in humans and related species. The prototype molecule for this process must be considered to be hemoglobin A Ic (Hb A Ic ), as this was the first protein recognized to be nonenzymatically glycosylated. Glucose reacts to form a schiff base with NH 2 -terminus of the β chain of Hb A, and subsequently undergoes an amadori rearrangement to yield 1-amino- 1-deoxyfructose. This modified hemoglobin, named Hb A Ic, is a normal red cell constituant present in increased concentration in patients with diabetes mellitus. Hb A Ic is synthesized throughout the life of the erythrocyte in a slow, nearly irreversible raction. The rate of synthesis is a function of blood glucose concentration. These properties of Hb A Ic combine to make it an indicator molecule whose concentration at one point in time reflects the patient's mean blood glucose level for the preceding month. This gives Hb A Ic a unique and invaluable role in clinical medicine, for it is the only known parameter that accurately assesses long term carbohydrate control. While Hb A Ic itself is not likely to have deleterious effects, the nonenzymatic glycosylation of other proteins may result in altered enzymatic activity, solubility, antigenicity etc., and thereby result in many of the clinical sequelae of long-standing diabetes. In this regard, lens proteins undergo increased glycosylation in high carbohydrate environments, and such glycosylation increases the ease with which the proteins oxidize to form high molecular weight aggregates and opacities. In fact, nonenzymatic glycosylation may play a major role in the normal aging process as the complications of diabetes are frequently considered to resemble accelerated aging.