Brodowsky I D, Hamberg M, Oliw E H
Department of Pharmaceutical Biosciences, Uppsala University Biomedical Center, Sweden.
Eur J Pharmacol. 1994 Mar 11;254(1-2):43-7. doi: 10.1016/0014-2999(94)90368-9.
Linoleic acid is converted to 8R-hydroperoxylinoleic acid by the soluble 8R-dioxygenase of the fungus Gaeumannomyces graminis. Effects of different lipoxygenase inhibitors on the 8R-dioxygenase were evaluated. Three hydroxamic acid derivatives were investigated. BW A4C (N-(3-phenoxycinnamyl)acetohydroxamic acid) was the most potent with an IC50 of 0.2 microM, followed by zileuton (3-10 microM) and linoleate-hydroxamic acid (0.02 mM). Two other lipoxygenase inhibitors, nordihydroguaiaretic acid and eicosatetraynoic acid, were less potent (IC50 0.09 and 0.15 mM, respectively). The 8R-dioxygenase was also strongly inhibited by commonly used buffer additives, dithiothreitol, beta-mercaptoethanol and phenylmethanesulfonyl fluoride. G. graminis also contains a hydroperoxide isomerase, which converts 8R-hydroperoxylinoleic acid to 7S,8S-dihydroxylinoleic acid. Ammonium sulphate precipitation and gel filtration indicated that the dioxygenase and the hydroperoxide isomerase activities could be separated.
真菌禾顶囊壳菌的可溶性8R-双加氧酶可将亚油酸转化为8R-氢过氧化亚油酸。评估了不同脂氧合酶抑制剂对8R-双加氧酶的影响。研究了三种异羟肟酸衍生物。BW A4C（N-(3-苯氧基肉桂基)乙酰异羟肟酸）活性最强，IC50为0.2微摩尔，其次是齐留通（3 - 10微摩尔）和亚油酸异羟肟酸（0.02毫摩尔）。另外两种脂氧合酶抑制剂，去甲二氢愈创木酸和二十碳四炔酸，活性较弱（IC50分别为0.09和0.15毫摩尔）。常用的缓冲添加剂二硫苏糖醇、β-巯基乙醇和苯甲基磺酰氟也能强烈抑制8R-双加氧酶。禾顶囊壳菌还含有一种氢过氧化物异构酶，可将8R-氢过氧化亚油酸转化为7S,8S-二羟基亚油酸。硫酸铵沉淀和凝胶过滤表明双加氧酶活性和氢过氧化物异构酶活性可以分离。
