P HYDROXYPHENYLACETALDEHYDE, MAJOR PRODUCT OF L TYROSINE OXIDATION

P 羟基苯乙醛，L 酪氨酸氧化的主要产物

• 批准号: 6486704
• 负责人: STANELY L HAZEN
• 金额: $ 15.75万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6486704
• 关键词: biomedical resource; cardiovascular system; enzymes; human tissue; lipids; minerals; proteins; spectrometry

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.

活化的人吞噬细胞利用髓过氧化物酶-H2 O2-Cl 将L-酪氨酸转化为两亲性醛的系统， 对羟基苯乙醛（pHA）。 我们已经研究过 pHA与蛋白质共价反应，这可能在 修饰炎症部位的靶点。 快速纯化pHA 与蛋白质赖氨酸残基的类似物Δ 2-乙酰赖氨酸反应。 在用NaCNBH 3还原后，反应产物被鉴定为 通过1H NMR光谱法测定Na-乙酰基-N3-对羟基苯乙基赖氨酸， 质谱分析法来 对羟基苯乙基赖氨酸（pHA-赖氨酸） 同样在暴露于l-酪氨酸的BSA上形成， 髓过氧化物酶_H_2O_2-Cl系统。 BSA和L-酪氨酸与 各种体外氧化系统表明，pHA-赖氨酸 是髓过氧化物酶修饰蛋白质的特异性标志物。 在暴露于活化的中性粒细胞的BSA中形成pHA-赖氨酸， L-酪氨酸 因为pHA-赖氨酸是蛋白质的特异性标记物， 通过髓过氧化物酶修饰，其鉴定可精确定位 吞噬细胞在体内造成氧化损伤的靶点。