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髓过氧化物酶:中性粒细胞氧化产物生成的关键调节因子。

Myeloperoxidase: a key regulator of neutrophil oxidant production.

机构信息

a Free Radical Research Group, Department of Pathology , Christchurch School of Medicine , Christchurch , New Zealand.

出版信息

Redox Rep. 1997 Feb;3(1):3-15. doi: 10.1080/13510002.1997.11747085.

DOI:10.1080/13510002.1997.11747085
PMID:27414766
Abstract

Myeloperoxidase plays a fundamental role in oxidant production by neutrophils. This heme enzyme uses hydrogen peroxide and chloride to catalyze the production of hypochlorous acid, which is the major strong oxidant generated by neutrophils in appreciable amounts. In addition to chlorination, myeloperoxidase displays several other activities. It readily oxidizes thiocyanate to hypothiocyanite, converts a myriad of organic substrates to reactive free radicals, and hydroxylates aromatic compounds. Depending on the concentration of its competing substrates and the conditions of the local environment, myeloperoxidase could substantially affect oxidant production by neutrophils. Superoxide is undoubtedly a physiological substrate for myeloperoxidase. Its interactions with the enzyme are key factors in determining how neutrophils use superoxide to kill pathogens and promote inflammatory tissue damage. Superoxide modulates the chlorination and peroxidation activities of myeloperoxidase. It also reacts with the enzyme to form oxymyeloperoxidase which is catalytically active and hydroxylates phenolic substrates. Myeloperoxidase reacts rapidly with nitric oxide and peroxynitrite so that at sites of inflammation there is a strong possibility that these reactions will impact on oxidative damage caused by neutrophils. Under certain conditions, many substrates of myeloperoxidase act as inhibitors and regulate oxidant production by the enzyme. Given the numerous reactions of myeloperoxidase, all its activities should be considered when assessing the injurious oxidants produced by neutrophils.

摘要

髓过氧化物酶在中性粒细胞产生氧化剂中起着基本作用。这种血红素酶利用过氧化氢和氯离子催化次氯酸的产生,次氯酸是中性粒细胞大量产生的主要强氧化剂。除氯化作用外,髓过氧化物酶还具有几种其他活性。它很容易将硫氰酸盐氧化为次硫氰酸盐,将无数有机底物转化为活性自由基,并使芳香族化合物羟基化。根据其竞争底物的浓度和局部环境的条件,髓过氧化物酶可能会极大地影响中性粒细胞产生氧化剂。超氧化物无疑是髓过氧化物酶的生理底物。其与酶的相互作用是决定中性粒细胞如何利用超氧化物杀死病原体并促进炎症性组织损伤的关键因素。超氧化物调节髓过氧化物酶的氯化和过氧化物酶活性。它还与酶反应形成具有催化活性的氧合髓过氧化物酶,并使酚类底物羟基化。髓过氧化物酶与一氧化氮和过氧亚硝酸盐迅速反应,因此在炎症部位,这些反应很可能会影响中性粒细胞引起的氧化损伤。在某些条件下,髓过氧化物酶的许多底物作为抑制剂起作用,并调节酶产生氧化剂。鉴于髓过氧化物酶的众多反应,在评估中性粒细胞产生的有害氧化剂时,应考虑其所有活性。

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