Hayashi Takaaki, Uchida Koji, Takebe Gen, Takahashi Kazuhiko
Hokkaido Institute of Public Health, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0819, Japan.
Free Radic Biol Med. 2004 Apr 15;36(8):1025-33. doi: 10.1016/j.freeradbiomed.2004.01.006.
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.
4-羟基-2-壬烯醛（HNE）和丙二醛（MDA）是脂质过氧化作用中广为人知的有毒产物。磷脂酰胆碱醛也被认为是磷脂酰胆碱的氧化产物。这些化合物在体内的形成机制一直是个长期存在的问题。我们观察到，血红蛋白（高铁血红蛋白、高铁肌红蛋白和细胞色素c）与含有氢过氧亚油酰基残基的1-棕榈酰-2-（13-氢过氧-顺-9，反-11-十八碳二烯酰）磷脂酰胆碱（PLPC-OOH）快速反应，生成了HNE、MDA以及磷脂酰胆碱醛1-棕榈酰-2-（9-氧代壬酰）磷脂酰胆碱。高铁血红蛋白、高铁肌红蛋白和细胞色素c在与PLPC-OOH孵育10分钟后，由分解的PLPC-OOH生成HNE和MDA的效率（摩尔产率）分别为：HNE为1.6%、1.0%和1.0%，MDA为1.2%、0.6%和0.9%。当1-棕榈酰-2-亚油酰基磷脂酰胆碱与脂氧化酶和高铁血红蛋白一起孵育时，观察到了HNE和磷脂酰胆碱醛1-棕榈酰-2-（9-氧代壬酰）磷脂酰胆碱的形成。当用1-棕榈酰-2-花生四烯酰基磷脂酰胆碱代替1-棕榈酰-2-亚油酰基磷脂酰胆碱时，得到了磷脂酰胆碱醛1-棕榈酰-2-氧代戊酰基磷脂酰胆碱。这些数据表明，HNE和磷脂酰胆碱醛可能通过脂氧合酶和血红蛋白由磷脂酰胆碱快速形成。此外，由脱氧胆酸和熊去氧胆酸将高铁血红蛋白转化而来的高铁血红素，对HNE有显著的分解作用。这些结果表明，血红蛋白与HNE的形成和分解都有关。
