Chemical Modification Induced by Glycation Increased Lysine Binding Site Activity of Human Serum Lipoprotein (a)

Lipoprotein (a) is a major and independent risk factor for cardiovascular disease. The pathogenicity of Lp(a) as a risk factor may depend upon its Lysine binding site(LBS) activity. It is suggested that non enzymatic glycation of Lp(a) resulting from high plasma glucose level found in diabetic patients may be one of the factors contributing to the severity of this disease. The purpose of this research was to study the effect of glycation on Lysine binding site activity of lipoprotein(a).

Materials & Methods: Lp(a) was glycated by incubation of 100 ml serum in vitro with 0.25 to 350 mmol of glucose for 10 days at 37oC. Glycated Lp(a) was separated by using m–aminobronate affinity column chromatography and Lysine binding site properties of the glycated Lp(a) were compared with native Lp(a) by using lysine sepharose affinity chromatography.

Results: Glucose uptake by Lp(a) was linear as a function of concentration and time up to 7 days for all given concentrations. Glycation increased the negative charge of Lp(a) as monitored by electrophoresis and increased the affinity of Lp(a) for Lysine sepharose affinity column chromatography.

Conclusion: Chemical modification induced by glycation of lp(a) affected its lysine binding site activity and increased LP(a) lysine positive subspecies.Therefore it is suggested that nonenzymatic glycation of Lp(a) may contribute to premature atherogenesis of patients with diabetes mellitus by increasing its LBS activity. and diverting lipoprotein catabolism from non-athero genic to atherogenic pathways.