Aldehydes from n-6 fatty acid peroxidation. Effects on aminophospholipids.
4-Hydroxy-nonenal (4-HNE) is a major by-product of n-6 fatty acid peroxidation. It has been described to covalently bind biomolecules expressing primary amine, especially the Lys residues in proteins. Low-density lipoproteins (LDL) are well-described macromolecules to be modified by 4-HNE, making them available to scavenger receptors on macrophages. Those macrophages then become foam cells and play an active role in atherogenesis. This paper reports on the covalent binding of 4-HNE to phosphatidylethanolamine (PE), a major aminophospholipid in biological membranes. In contrast, phosphatidylserine (PS) is virtually not modified by 4-HNE. One stable adduct, the Michael adduct PE/4-HNE is a poor substrate of secreted phospholipase A(2) and is not cleaved by phospholipase D. Plasmalogen PE, an important subclass of PE, is covalently modified by 4-HNE as well, but appears to be further degraded on its sn-1 position, the alkenyl chain, which might alter the antioxidant potential of the molecule. An aldehyde homologous to 4-HNE has been characterized as a breakdown product of 12-hydroperoxyeicosatetraenoic acid (12-HpETE) and named 4-hydroxy-2E,6Z-dodecadienal (4-HDDE). This compound as well as 4-HNE was detected in human plasma. Finally, 4-HDDE appears almost 3-fold more active than 4-HNE to make covalent adducts with PE. We conclude that 4-HNE and 4-HDDE are two biologically relevant markers of n-6 fatty acid peroxidation that may alter the phospholipid-dependent cell signaling.
D000447:Aldehydes / Q000378:metabolism*; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D015227:Lipid Peroxidation; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*
D000447:Aldehydes; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D010743:Phospholipids; D001092:Arachidonate 12-Lipoxygenase; D010739:Phospholipase D; C027576:4-hydroxy-2-nonenal