Fibrinogen glycosylation

No alteration of protein half-life has been detected with glycosylated albumin (39) and ferritin (51). However, Jones and Peterson (45) found that fibrinogen survival, which was reduced in diabetic patients with elevated glycemia, could be increased to normal value shortly after insulin therapy. This suggests that a labile Schiff base could play a role in the regulation of fibrinogen turnover. 

There are a few examples where mixtures of complex oligosaccharide have been isolated from natural sources such as bovine fetuin, porcine fibrinogen or conalbumin, and the mixture converted to the glycosyl amine and then coupled to an amino acid before separation of the individual components by HPLC. In one example described, 15 N-linked... 

Specific lysine residues of antithrombin III bind heparin to act as a major inhibitor of serine-protease plasma coagulation factors. Nonenzymatic glycosylation of antithrombin III, by preferentially binding to lysines and decreasing the affinity of antithrombin III for heparin, will decrease its thrombin inhibitory activity (B3I, C7). In vivo inhibition of antithrombin III occurs in type I diabetics (D27, S35). Decreased antithrombin III and fibrinogen activity in severe diabetics can be reversed by heparin infusion. 

The excess vessel wall fibrin accumulation and atherosclerosis seen as a long-term complication of diabetes may well result from the glycosylation-induced inhibition in fibrinogen (fibrin)-plasmin degradative function and heparin-catalyzed antithrombin III activity. 

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