Role of lysines in mediating interaction of modified low density lipoproteins with the scavenger receptor of human monocyte macrophages.
The ability of the scavenger receptor of human monocyte macrophages to recognize human low density lipoproteins (LDL) progressively modified by three lysine-specific reagents, malondialdehyde, acetic anhydride, or succinic anhydride, has been investigated. Regardless of the reagent utilized, receptor-mediated uptake was dependent upon modification of greater than 16% of the peptidyl lysines rather than upon the net negative charge of derivatized LDL. Rates of lysosomal hydrolysis of acetyl-LDL and succinyl-LDL increased as a function of progressive modification and reflected the amount of derivatized LDL binding to the receptor. Succinylation or acetylation of greater than 60% of the lysines was necessary to attain maximal ligand binding, internalization, and degradation. In contrast, modification of only 16% of the peptidyl lysines by malondialdehyde resulted in maximal levels of binding, uptake, and hydrolysis. The expression of receptor recognition site(s) appears to depend upon the charge modification of critical lysine residues of the LDL protein rather than the net negative charge of the lipoprotein complex. Malondialdehyde, a bifunctional reactant, may modify surface and sequestered lysines concomitantly and thus promote efficient formation of the recognition site(s).
D000089:Acetic Anhydrides / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D008077:Lipoproteins, LDL / Q000097:blood*; D008239:Lysine / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008315:Malondialdehyde / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011973:Receptors, LDL; D013387:Succinic Anhydrides / Q000494:pharmacology
D000089:Acetic Anhydrides; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D013387:Succinic Anhydrides; C031800:acetic anhydride; D008315:Malondialdehyde; C031801:succinic anhydride; D008239:Lysine