Arachidonate 12-lipoxygenases with reference to their selective inhibitors

Biochem Biophys Res Commun. 2005 Dec 9;338(1):122-7. doi: 10.1016/j.bbrc.2005.08.214. Epub 2005 Sep 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 12-Lipoxygenase / chemistry
  • Arachidonate 12-Lipoxygenase / genetics
  • Arachidonic Acid / chemistry
  • Arachidonic Acid / metabolism*
  • Catechin / analogs & derivatives
  • Catechin / pharmacology
  • Humans
  • Lipoxygenase Inhibitors*
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / genetics
  • Structure-Activity Relationship
  • Swine

Substances

  • Lipoxygenase Inhibitors
  • Recombinant Proteins
  • gallocatechin gallate
  • Arachidonic Acid
  • Catechin
  • Arachidonate 12-Lipoxygenase