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 cardiovasculardi sease. the pathogenicity of lp(a) as arisk factor may depend upon its lysin ebinding site(lbs) activity. it is suggested thatnon enzymatic glycation of lp(a) resulting fromhigh plasma glucose level found in diabetic patientsmay be one of the factors contributing tothe severity of this disease. the purpose of thisresearch was to study the effect of glycation onlysine binding site activity of lipoprotein(a).materials & methods: lp(a) was glycated b y in cubationof 100 ml serum in vitro with 0.25 to 350mmol of glucose for 10 days at 370c. glycatedlp(a) was separated by using m-aminobronateaffinity column chromatography an d lysinebinding site properties of the glycated lp (a)were compared with native lp(a) by using ly sinesepharose affinity chromatography.results: glucose uptake by lp(a) was linear as afunction of concentration and time up to 7 da ysfor all given concentrations. glycation increasedthe negative charge of lp(a) as moni tored byelectrophoresis and increased the affin ity oflp(a) for lysine sepharose affini ty columnchromatography.conclusion: chemical modification induced by glycation of lp(a) affected its lysine bindi ng siteactivity and increased lp(a) lysine positive subspecies.th erefore it is suggested th at nonenzymaticgly catio n of lp(a) may contr ibut e to prematureatherogenesis of patients with diabetesmell itu s by increasi ng it s lbs activity. and divertinglipoprotein catabolism from non -ath erogeni c to atherogenic pathways.