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

Lipoprotein (a) is a major and in de- L pendent risk factor fo r cardiovascular di sease. The pathogenicity of Lp(a) as a risk factor may depend upon its Lysin e 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 b y in cubation of 100 ml serum in vitro with 0.25 to 350 mmol of glucose for 10 days at 370C. Glycated Lp(a) was separated by using m-aminobronate affinity column chromatography an d Lysine binding site properties of the glycated Lp (a) were compared with native Lp(a) by using ly sine sepharose affinity chromatography. Results: Glucose uptake by Lp(a) was linear as a function of concentration and time up to 7 da ys for all given concentrations. Glycation increased the negative charge of Lp(a) as moni tored by electrophoresis and increased the affin ity of Lp(a) for Lysine sepharose affini ty column chromatography. Conclusion: Chemical modification induced by glycation of lp(a) affected its lysine bindi ng site activity and increased LP(a) lysine positive subspecies. Th erefore it is suggested th at nonenzymatic gly catio n of Lp(a) may contr ibut e to premature atherogenesis of patients with diabetes mell itu s by increasi ng it s LBS activity. and diverting lipoprotein catabolism from non -ath ero geni c to atherogenic pathways.