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Low Density Lipoprotein Derivatization by Acetaldehyde Affects Lysine Residues and the B/E Receptor Binding Affinity
Author(s) -
Kervinen Kari,
Savolainen Markku J.,
Tikkanen Matti J.,
Kesälniemi Y. Antero
Publication year - 1991
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1991.tb05210.x
Subject(s) - chemistry , acetaldehyde , ldl receptor , low density lipoprotein , lysine , biochemistry , receptor , lipoprotein , pcsk9 , amino acid , ethanol , cholesterol
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 end lipid composition of LDL, but the AcA concentration used in the incubation correlated strongly with the electrophoretic mobility of acetaidehyde‐treated LDL (AcA‐LDL) (r = 0.97, p<0.001) and the percentage of the free amino groups in AcA‐LDL (r = ‐0.90, p < 0.01). Amino acid analysis of AcA‐LDL showed that iysine 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 lmmu‐nological recognition of the LDL receptor binding region and its vicinity. Also, the binding affinity of AcA‐LDL to B/E receptors cor related negatively with the percentage of modified iysine residues in AcA‐LDL (r = ‐0.96, p < 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 nonphysiologicaiiy high concentrations of AcA, and, therefore, the role of the present findings in vivo remains uncertain. Alcohol, Acetaldehyde, Lipoproteins, Proteins, Arteriosclerosis.