CHARACTER OF SCHIFF BASE FORMED IN REACTION OF P HYDROXYLPHENYLACETALDEHYDE

当醛修饰蛋白质时形成的加合物 与血管疾病和衰老的发病机制有关。我们的 以往的研究表明，对羟基苯乙醛(PHA)、 L的主要产物--髓过氧化物酶-氢对酪氨酸的氧化 吞噬细胞的过氧化氢-氯化物系统，共价改变 (-炎症部位赖氨酸残基的氨基。在这里，我们 报道称，PHA还与合成的氨基发生反应 磷脂和红细胞模型系统。快原子轰击 乙醇胺甘油磷脂的质谱分析 丝氨酸甘油磷脂与PHA和NaCNBH3孵育的检测 与还原磷脂Schiff一致的共价加合物 碱加合物。我们确认了醛与 用~1H核磁共振和质谱学分析极性的氨基 头部组从修饰和降低的亲本脂质中恢复。 当我们暴露磷脂模型系统时 和细胞膜到生理水平的L-酪氨酸和 髓过氧化物酶-过氧化氢-氯化物体系 用NaCNBH3处理，得到了PHA的还原席夫碱加合物 乙醇胺甘油磷脂和丝氨酸甘油磷脂 (分别为PHA-PE和PHA-PS)。所需的反应 髓过氧化物酶、过氧化氢、L酪氨酸和氯离子；它 被过氧化氢酶或血红素毒素抑制，表明体内存在一种过氧化物酶 这条小路。总而言之，这些结果表明，乙醛 由吞噬细胞的髓过氧化物酶系统产生 乙醇胺、甘油磷脂和丝氨酸的氨基修饰 甘油磷脂。因为氨基甘油磷脂是至关重要的 细胞膜的成分和循环中的脂蛋白，如低密度脂蛋白， 类似的反应可能在引发或 炎症部位的疾病进展。

The adducts that form when aldehydes modify proteins have been implicated in the pathogenesis of vascular disease and aging. Our previous studies indicated that p-hydroxyphenylacetaldehyde (pHA), the major product of L-tyrosine oxidation by the myeloperoxidase-hydrogen peroxide-chloride system of phagocytes, covalently modifies the (-amino group of lysine residues at sites of inflammation. Here, we report that pHA also reacts with the amino group of synthetic phospholipids and red blood cell model systems. Fast atom bombardment mass spectrometric analysis of ethanolamine glycerophospholipid or serine glycerophospholipid incubated with pHA and NaCNBH3 detected covalent adducts that were consistent with reduced phospholipid Schiff base adducts. We confirmed the reaction of the aldehyde with the amino group through 1H NMR and mass spectrometric analysis of polar head groups recovered from the modified and reduced parent lipid. When we exposed phospholipid model systems and cell membranes to physiological levels of L-tyrosine and the myeloperoxidase-hydrogen peroxide-chloride system followed by treatment with NaCNBH3, we obtained reduced Schiff base adducts of pHA with ethanolamine glycerophospholipid and serine glycerophospholipid (pHA-PE and pHA-PS, respectively). The reaction required myeloperoxidase, hydrogen peroxide, L-tyrosine and chloride ion; it was inhibited by catalase or heme poisons, implicating a peroxidase in the pathway. Collectively, these results demonstrate that an aldehyde generated by the myeloperoxidase system of phagocytes can covalently modify the amino groups of ethanolamine glycerophospholipid and serine glycerophospholipid. Because amino glycerophospholipids are critical components of cell membranes and circulating lipoproteins such as LDL, similar reactions may play important roles in the initiation or progression of disease at sites of inflammation.