Relevance of different apolipoprtein content in homocysteine binding to plasma lipoproteins

Background and aims: In plasma, homocysteine (Hcy) circulates free or bound to proteins (Pb-Hcy). Our study sets out to assess the lipoprotein-Hcy (LP-Hcy) binding in vivo and the possible influence of different apolipoprotein content in this binding. Methods: In 34 healthy subjects fasting plasma lipoprotein (Sequential ultra-centrifugation) and correspondent apolipoprotein (apo A-I, apo A-II, apo C-II, apo C-III, apo B, apo(a) and apo E) content (Immunoturbidimetric assay), and Hcy (HPLC) bound to different plasma protein fractions were assessed; ten subjects underwent a methionine oral load in order to evaluate Pb-Hcy and LP-Hcy modifications after induction of hyperhomocysteinemia (HHcy). Results: Pb-Hcy (mean values 9.22±1.7 mol/L) resulted 78% of total plasma Hcy (mean values 11.8±1.8 mol/L). Pb-Hcy distribution between the different fractions was as follows (mol/L): VLDL= 0.25 ± 0.08 (2.7 %); LDL= 0.88 ± 0.22 (9.5 %); HDL =1.40 ± 0.36 (15.2 %), Lipoprotein-Free Protein Fraction (LPDS) = 6.7 ± 1.2 (72.6 %). Hcy/protein ratios (mol / g of protein) of each protein fraction were: VLDL= 0.32 ± 0.19, LDL= 0.43 ± 0.37, HDL= 0.26 ± 0.18, LPDS < 0.1, this suggesting a higher binding capacity for Hcy of VLDL and LDL. This data was confirmed by the higher increase in Hcy content in LDL and VLDL (+76 and +90%, respectively vs. +36% and +3.1 % for HDL and LPDS fractions) after HHcy. Lp-Hcy binding significantly correlated with the apo B content of VLDL and LDL and Apo A-I content of HDL. Conclusions: An important fraction of Hcy circulates bound to LP (about 27% of Pb-Hcy); VLDL and LDL show the highest binding capacity for Hcy; this may be due to content in Apo B, a possible high capacity binding site for Hcy (great availability of free cysteine and lysine residuals).