Arachidonate 12-lipoxygenases with reference to their selective inhibitors.
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 microM. The compound was much less active with 12-lipoxygenase of leukocyte-type, 15-, 8-, and 5-lipoxygenases, and cyclooxygenases-1 and -2.
Yamamoto
Shozo
S
Department of Food and Nutrition, Faculty of Home Economics, Kyoto Women's University, Imakumano, Higashiyama-ku, Kyoto 605-8501, Japan. yamamosh@kyoto-wu.ac.jp
Katsukawa
Michiko
M
Nakano
Ayumi
A
Hiraki
Emi
E
Nishimura
Kohji
K
Jisaka
Mitsuo
M
Yokota
Kazushige
K
Ueda
Natsuo
N
D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000737:chemistry / Q000235:genetics; D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D016859:Lipoxygenase Inhibitors; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D013329:Structure-Activity Relationship; D013552:Swine
D016859:Lipoxygenase Inhibitors; D011994:Recombinant Proteins; C417940:gallocatechin gallate; D016718:Arachidonic Acid; D002392:Catechin; D001092:Arachidonate 12-Lipoxygenase