Nonenzymatic glycosylation of protein: Relevance to diabetes

Glucose can react nonenzymatically with proteins to form stable covalent linkages. The most abundant minor hemoglobin component in human red cells is hemoglobin A_Ic: glucose is attached to the N-terminal amino group of the β chain by a ketoamine linkage. Hemoglobin A_Ic is increased two to threefold in the red cells of diabetic patients. It is formed slowly and continuously throughout the 120-day lifespan of the red cell. Measurement of hemoglobin A_Ic provides an index of average blood glucose levels over the preceding two or three months. Thus, hemoglobin A_Ic has proved to be useful in assessing diabetic control and, perhaps, in screening people for diabetes. Many other proteins, such as lens crystallins, collagen and proteins in serum and in red cell membrane, are modified by nonenzymatic glycosylation. This structural alteration may lead to impaired protein function and, perhaps, contribute to the long-term complications of diabetes.