Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, AL 35294, USA.
Free Radic Biol Med. 2012 Nov 15;53(10):1954-9. doi: 10.1016/j.freeradbiomed.2012.08.597. Epub 2012 Sep 12.
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 (H(2)O(2)), 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 H(2)O(2). Under physiological pH and concentrations of halides (100μM KBr, 100μM KSCN, and 100mM NaCl), VPO1 utilizes approximately 45% of H(2)O(2) 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.
血红素过氧化物酶家族包括人类中的 8 个成员。血红素过氧化物酶的生理和病理生理作用尚未得到很好的理解。吞噬细胞衍生的髓过氧化物酶 (MPO) 在过氧化氢 (H₂O₂) 的存在下利用氯和溴，生成次氯酸和次溴酸，这两种强氧化剂已知可杀死入侵的病原体。血管过氧化物酶 1 (VPO1) 是血红素过氧化物酶家族的新成员；VPO1 在心血管系统、肺、肝、胰腺和脾中高度表达。然而，VPO1 的功能作用尚未确定。在本报告中，我们证明了 VPO1 能够催化次卤酸的形成，并对其酶学特性进行了表征。VPO1 与 MPO 相似，但与乳过氧化物酶不同，能够在 H₂O₂存在下生成次氯酸、次溴酸和次硫氰酸。在生理 pH 和卤化物浓度下（100μM KBr、100μM KSCN 和 100mM NaCl），VPO1 利用约 45%的 H₂O₂生成次溴酸，35%生成次硫氰酸，18%生成次氯酸。VPO1 的比活性约为 MPO 的 10-70 倍，具体取决于特定的底物。这些研究表明，VPO1 的酶学性质和底物特异性与 MPO 相似；然而，VPO1 相对于 MPO 的催化速率常数明显较低，这表明这种新型血红素过氧化物酶可能具有其他生理作用。
