P HYDROXYPHENYLACETALDEHYDE, MAJOR PRODUCT OF L TYROSINE OXIDATION

活化的人吞噬细胞使用髓过氧化物酶-H_2O_2-氯 将L酪氨酸转化为两亲性醛的系统， 对羟基苯乙醛(PHA)。我们已经探索了这种可能性 PHA与蛋白质发生共价反应，这可能在 在炎症部位修饰靶点。快速提纯PHA 与A2-乙酰赖氨酸反应，A2-乙酰赖氨酸是蛋白质赖氨酸残基的类似物。 用NaCNBH3还原后的反应产物经鉴定为 Na-乙酰基-N3-对羟基苯乙基赖氨酸的~1H核磁共振波谱和 质谱学。对羟基苯乙基赖氨酸(PHA-赖氨酸) 同样在暴露于L酪氨酸的牛血清白蛋白上形成 髓过氧化物酶-H_2O_2-氯体系。牛血清白蛋白与L酪氨酸的孵育 多种体外氧化系统证明PHA-赖氨酸 是髓过氧化物酶修饰蛋白质的特异性标记物。 在活化的中性粒细胞作用下，BSA中形成了PHA-赖氨酸 L-酪氨酸。因为PHA-赖氨酸是蛋白质的特定标记物 髓过氧化物酶的修饰，其鉴定可准确定位 吞噬细胞在体内造成氧化损伤的靶点。

Activated human phagocytes employ the myeloperoxidase-H2O2-Cl system to convert L-tyrosine into the amphipathic aldehyde, p-hydroxyphenylacetaldehyde (pHA). We have explored the possibility that pHA covalently reacts with proteins, which may play a role in modifying targets at sites of inflammation. Purified pHA rapidly reacted with A2-acetyllysine, an analog of protein lysine residues. After reductin with NaCNBH3 the reaction product was identified as Na-acetyl-N3-p-hydroxyphenylethyllysine by 1H NMR spectroscopy and mass spectrometry. p-Hydroxyphenylethyllysine (pHA-lysine) was likewise formed on BSA exposed to l-tyrosine and the myeloperoxidase_H2O2-Cl system. Incubation of BSA and L-tyrosine with a variety of in vitro oxidation systems demonstrated that pHA-lysine is a specific marker for protein modification by myeloperoxidase. pHA-Lysine was formed in BSA exposed to activated neutrophils and L-tyrosine. Because pHA-lysine is a specific marker of protein modificat ion by myeloperoxidase, its identification may pinpoint targets where phagocytes inflict oxidative damage in vivo.