The nonenzymatic glycosylation of hemoglobin has served as a model for the postsynthetic modification of protein by glucose. From these studies it has been proposed that nonenzymatic glycosylation of proteins could play a role in the development of the complications associated with diabetes mellitus. The first tissue in which an attempt has been made to link nonenzymatic glycosylation and a pathologic sequela is the ocular lens and the formation of cataracts. Incubation of lens proteins with glucose in vitro leads to nonenzymatic glycosylation, intermolecular disulfide bond formation, and protein aggregates that defract light. These findings mimic the state of proteins found in the diabetic lens. With longer incubation times, these nonenzymatically glycosylated proteins can undergo further rearrangements to form yellow-brown pigments (nonenzymatic browning) that act as molecular cross-links. From a number of physical and chemical studies it appears that these pigments formed in vitro are similar to those found in senile lenses.
Thus the nonenzymatic browning of glycosylated proteins that has been described in stored foodstuffs might well be occurring in vivo. Such protein modifications, which are essentially irreversible, could have significant effects on the aging of long-lived proteins and the general aging process of biologic systems.