Egan R W, Hagmann W K, Gale P H
Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065.
Agents Actions. 1990 Mar;29(3-4):266-76. doi: 10.1007/BF01966457.
Control of myeloperoxidase (MPO) may be an important consideration in disorders where excessive PMN elastase activity is a significant factor. There are, however, two mechanisms for the apparent regulation of MPO: 1) inhibit the enzyme directly, and ii) prevent the ensuing HOC1 induced oxidation by using a surrogate reducing agent. Appropriate methodology has been devised to distinguish true MPO inhibitors. With the exception of NaN3, many MPO inhibitors fall into the latter category and do not actually regulate the enzyme. Several potent organic inhibitors have been discovered, which, because of their structural selectivity, appear to associate specifically with a binding site on the enzyme, rather than attaching indiscriminately to a hydrophobic domain. By controlling the enzyme, these compounds protect alpha-1-PI from MPO induced damage, and could serve better than antioxidants to define the role of MPO in elastase induced injury.
在中性粒细胞弹性蛋白酶活性过高是一个重要因素的疾病中，髓过氧化物酶（MPO）的调控可能是一个重要的考虑因素。然而，MPO的表观调控有两种机制：1）直接抑制该酶，以及2）通过使用替代还原剂防止随后由次氯酸（HOC1）诱导的氧化。已经设计出适当的方法来区分真正的MPO抑制剂。除了叠氮化钠（NaN3）之外，许多MPO抑制剂属于后一类，实际上并不能调控该酶。已经发现了几种有效的有机抑制剂，由于它们的结构选择性，似乎与该酶上的一个结合位点特异性结合，而不是随意附着在疏水结构域上。通过控制该酶，这些化合物可保护α-1-抗胰蛋白酶（alpha-1-PI）免受MPO诱导的损伤，并且在确定MPO在弹性蛋白酶诱导的损伤中的作用方面可能比抗氧化剂发挥更好的作用。
