Rapid formation of 4-hydroxy-2-nonenal, malondialdehyde, and phosphatidylcholine aldehyde from phospholipid hydroperoxide by hemoproteins.

4-Hydroxy-2-nonenal (HNE) and malondialdehyde (MDA) are well-known toxic products of lipid peroxidation. Phosphatidylcholine aldehydes are also known as oxidation products of phosphatidylcholine. The mechanism of the formation of these compounds in vivo has been a long-standing question. We observed that the rapid reaction of hemoproteins (methemoglobin, metmyoglobin, and cytochrome c) with 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl) phosphatidylcholine (PLPC-OOH), having a hydroperoxylinoleoyl residue, generated HNE, MDA, and the phosphatidylcholine aldehyde 1-palmitoyl-2-(9-oxononanoyl) phosphatidylcholine. The efficiencies (mol% yield) of the formation of HNE and MDA from decomposed PLPC-OOH by methemoglobin, metmyoglobin, and cytochrome c after incubation for 10 min were 1.6, 1.0, and 1.0% for HNE and 1.2, 0.6, and 0.9% for MDA, respectively. When 1-palmitoyl-2-linoleoyl phosphatidylcholine was incubated with lipoxidase and methemoglobin, the formation of HNE and the phosphatidylcholine aldehyde 1-palmitoyl-2-(9-oxononanoyl) phosphatidylcholine was observed. When 1-palmitoyl-2-arachidonyl phosphatidylcholine was used instead of 1-palmitoyl-2-linoleoyl phosphatidylcholine, the phosphatidylcholine aldehyde 1-palmitoyl-2-oxovaleroyl phosphatidylcholine was obtained. These data suggest that HNE and phosphatidylcholine aldehydes might be rapidly formed from phosphatidylcholine by lipoxygenase and hemoproteins. Furthermore, hemichrome, converted from methemoglobin by deoxycholic acid and ursodeoxycholic acid, showed marked decomposition of HNE. These results suggest that hemoproteins are related to both the formation and the decomposition of HNE.