Vascular peroxidase 1 catalyzes the formation of hypohalous acids: characterization of its substrate specificity and enzymatic properties.
Vascular peroxidase 1 catalyzes the formation of hypohalous acids: characterization of its substrate specificity and enzymatic properties.
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DOI：
10.1016/j.freeradbiomed.2012.08.597
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发表时间：
2012-11-15
影响因子：
7.4
通讯作者：
Cheng, Guangjie
中科院分区：
文献类型：
--
作者：
Li, Hong;Cao, Zehong;Zhang, Guogang;Thannickal, Victor J.;Cheng, Guangjie
含血红素的过氧化物酶家族在人类中包括八个成员。含血红素的过氧化物酶的生理和病理生理作用还不清楚。吞噬细胞衍生的髓过氧化物酶（MPO）在过氧化氢（H2 O2）的存在下利用氯化物和溴化物来产生次氯酸和次溴酸，已知其是杀死入侵病原体的有效氧化物质。血管过氧化物酶1（VPO 1）是含血红素的过氧化物酶家族的新成员; VPO 1在心血管系统、肺、肝、胰腺和脾中高度表达。然而，VPO 1的职能作用尚未确定。在这份报告中，我们证明了VPO 1催化形成次卤酸的能力，并表征其酶学性质。VPO 1与MPO相似，但与乳过氧化物酶不同，在H2 O2存在下能够产生次氯酸、次溴酸和次硫氰酸。在生理pH和卤化物浓度（100 µM KBr、100 µM KSCN和100 mM NaCl）下，VPO 1利用约45%的H2 O2生成次溴酸，35%生成次硫氰酸，18%生成次氯酸。VPO 1的比活性比MPO低约10至70倍，具体取决于特定的底物。这些研究表明，VPO 1的酶性质和底物特异性与MPO相似;然而，VPO 1相对于MPO的催化速率常数显着降低，表明这种新型含血红素过氧化物酶可能具有其他生理作用。
The heme-containing peroxidase family comprises eight members in humans. The physiological and pathophysiological roles of heme-containing peroxidases are not well understood. Phagocyte-derived myeloperoxidase (MPO) utilizes chloride and bromide, in the presence of hydrogen peroxide (H2O2), to generate hypochlorous acid and hypobromous acid, potent oxidizing species that are known to kill invading pathogens. Vascular peroxidase 1 (VPO1) is a new member of the heme-containing peroxidase family; VPO1 is highly expressed in the cardiovascular system, lung, liver, pancreas, and spleen. However, functional roles of VPO1 have not been defined. In this report, we demonstrate the capacity for VPO1 to catalyze the formation of hypohalous acids, and characterize its enzymatic properties. VPO1, like MPO but unlike lactoperoxidase, is able to generate hypochlorous acid, hypobromous acid, and hypothiocyanous acid in the presence of H2O2. Under physiological pH and concentrations of halides (100 µM KBr, 100 µM KSCN, and 100 mM NaCl), VPO1 utilizes approximately 45% of H2O2 for the generation of hypobromous acid, 35% for hypothiocyanous acid, and 18% for hypochlorous acid. The specific activity of VPO1 is ~10- to 70-fold lower than that of MPO, depending on the specific substrate. These studies demonstrate that the enzymatic properties and substrate specificity of VPO1 are similar to MPO; however, significantly lower catalytic rate constants of VPO1 relative to MPO suggest the possibility of other physiologic roles for this novel heme-containing peroxidase.
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