Low density lipoprotein derivatization by acetaldehyde affects lysine residues and the B/E receptor binding affinity.
Acetaldehyde (AcA), the first metabolite in ethanol oxidation, forms covalent adducts with the free amino groups of various proteins. In this study, we examined how acetaldehyde modification affects the chemical and biological properties of the atherogenic low density lipoprotein (LDL). AcA modification did not alter the protein and lipid composition of LDL, but the AcA concentration used in the incubation correlated strongly with the electrophoretic mobility of acetaldehyde-treated LDL (AcA-LDL) (r = 0.97, p less than 0.001) and the percentage of the free amino groups in AcA-LDL (r = -0.90, p less than 0.01). Amino acid analysis of AcA-LDL showed that lysine was the predominant residue in LDL modified by AcA. Assays with monoclonal antibodies (MB47, 2b, 4G3, and C1.1) directed against different epitopes of the LDL apoprotein B suggested that AcA modification reduced the immunological recognition of the LDL receptor binding region and its vicinity. Also, the binding affinity of AcA-LDL to B/E receptors correlated negatively with the percentage of modified lysine residues in AcA-LDL (r = -0.96, p less than 0.001). The results suggest that AcA derivatizes the lysine residues of LDL, and thus decreases the B/E receptor binding affinity of LDL. However, major changes in LDL receptor binding were produced only with non-physiologically high concentrations of AcA, and, therefore, the role of the present findings in vivo remains uncertain.
Kervinen
K
K
Department of Internal Medicine, University of Oulu, Finland.
Savolainen
M J
MJ
Tikkanen
M J
MJ
Kesäniemi
Y A
YA
D000079:Acetaldehyde / Q000097:blood* / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000097:blood*; D000596:Amino Acids / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008239:Lysine / Q000032:analysis*; D011971:Receptors, Immunologic / Q000032:analysis / Q000187:drug effects*; D011973:Receptors, LDL / Q000032:analysis* / Q000187:drug effects*
D000596:Amino Acids; D008077:Lipoproteins, LDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D000079:Acetaldehyde; D008239:Lysine