Arachidonate 12-lipoxygenases with reference to their selective inhibitors
Arachidonate 12-lipoxygenases with reference to their selective inhibitors
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DOI：
10.1016/j.bbrc.2005.08.214
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发表时间：
2005-12-09
影响因子：
3.1
通讯作者：
Ueda, N
中科院分区：
文献类型：
--
作者：
Yamamoto, S;Katsukawa, M;Ueda, N
脂氧合酶是识别多不饱和脂肪酸的1-顺式，4-顺式-戊二烯的双加氧酶。该酶氧化作为底物的花生四烯酸的各种碳原子，并产生具有共轭二烯发色团的5-、8-、12-或15-氢过氧二十碳四烯酸。该酶分别称为5-、8-、12-或15-脂氧合酶。早些时候，我们发现了两种异构体的12-脂氧合酶，白细胞和血小板型酶，这是由底物特异性，催化活性，一级结构，基因内含子的大小，和抗原性区分。最近，表皮型酶被发现作为第三种亚型。已经尝试寻找12-脂氧合酶的同工酶特异性抑制剂，并且更早地，我们发现扁柏酚，一种环庚三烯酚酮，作为血小板型12-脂氧合酶的选择性的有效抑制剂。最近，我们测试了茶叶中的各种儿茶素，发现（-）-没食子儿茶素没食子酸酯是人血小板12-脂氧合酶的有效和选择性抑制剂，IC 50为0.14 μ M。该化合物对白细胞型的12-脂氧合酶、15-、8-和5-脂氧合酶以及环氧合酶-1和-2的活性要低得多。(c)2005年爱思唯尔公司All rights reserved.
Lipoxygenase is a dioxygenase recognizing a 1-cis,4-cis-pentadiene of polyunsaturated fatty acids. The enzyme oxygenates various carbon atoms of arachidonic acid as a substrate and produces 5-, 8-, 12- or 15-hydroperoxyeicosatetraenoic acid with a conjugated diene chromophore. The enzyme is referred to as 5-, 8-, 12- or 15-lipoxygenase, respectively. Earlier we found two isoforms of 12-lipoxygenase, leukocyte- and platelet-type enzymes, which were distinguished by substrate specificity, catalytic activity, primary structure, gene intron size, and antigenicity. Recently, the epidermis-type enzyme was found as the third isoform. Attempts have been made to find isozyme-specific inhibitors of 12-lipoxygenase, and earlier we found hinokitiol, a tropolone, as a potent inhibitor selective for the platelet-type 12-lipoxygenase. More recently, we tested various catechins of tea leaves and found that (-)-gallocatechin gallate was a potent and selective inhibitor of human platelet 12-lipoxygenase with an IC50 of 0.14 mu M. The compound was much less active with 12-lipoxygenase of leukocyte-type, 15-, 8-, and 5-lipoxygenases, and cyclooxygenases-1 and -2. (c) 2005 Elsevier Inc. All rights reserved.