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Biochem J. Feb 15, 1991; 274(Pt 1): 287–292.
PMCID: PMC1149951

Pseudoperoxidase activity of 5-lipoxygenase stimulated by potent benzofuranol and N-hydroxyurea inhibitors of the lipoxygenase reaction.


The purified 5-lipoxygenase from porcine leukocytes was found to catalyse the degradation of lipid hydroperoxides in the presence of potent inhibitors of the lipoxygenase reaction. Derivatives of diphenyl-N-hydroxyureas, 4-hydroxybenzofurans and 5-hydroxydihydrobenzofurans all stimulated the 5-lipoxygenase-mediated destruction of 13-hydroperoxyoctadecadienoic acid (13-HPOD). The reaction was dependent on inhibitor and hydroperoxide concentrations (1-10 microM) and could not be detected using heat-inactivated enzyme, when ATP and Ca2+ were omitted or when the hydroperoxide was replaced by the corresponding alcohol. The stability of the inhibitors during this pseudoperoxidase reaction was investigated by measuring the recoveries of 5-hydroxy-2-phenethyl-6-(3-phenoxypropyl)-2,3-dihydrobenzofuran and N-(4-chlorophenyl)-N-hydroxy-N'-(3-chlorophenyl)urea from the reaction mixtures using reverse-phase h.p.l.c. By using an equimolar concentration of 13-HPOD and inhibitor (10 microM) and under conditions where 50% of the 13-HPOD was consumed, the concentration of the benzofuranol decreased by 30%, whereas the N-hydroxyurea derivative could be completely recovered from the reaction mixture. A stimulation of the pseudoperoxidase reaction could be detected only with very effective inhibitors of leukotriene B4 biosynthesis by human leucocytes [IC50 (concn. causing 50% inhibition) less than 100 nM], but not with closely related structural analogues of lower potency or other inhibitors such as nordihydroguaiaretic acid, quercetin or the hydroxamate A-64077. These results demonstrate that 5-lipoxygenase possesses a pseudoperoxidase activity and indicate that potent inhibitors in both N-hydroxyurea and benzofuranol series can function as reducing agents for the enzyme.

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  • Borgeat P. Biochemistry of the lipoxygenase pathways in neutrophils. Can J Physiol Pharmacol. 1989 Aug;67(8):936–942. [PubMed]
  • Lau CK, Bélanger PC, Scheigetz J, Dufresne C, Williams HW, Maycock AL, Guindon Y, Bach T, Dallob AL, Denis D, et al. Synthesis and structure-activity relationships of a novel class of 5-lipoxygenase inhibitors. 2-(Phenylmethyl)-4-hydroxy-3,5-dialkylbenzofurans: the development of L-656,224. J Med Chem. 1989 Jun;32(6):1190–1197. [PubMed]
  • Yoshimoto T, Furukawa M, Yamamoto S, Horie T, Watanabe-Kohno S. Flavonoids: potent inhibitors of arachidonate 5-lipoxygenase. Biochem Biophys Res Commun. 1983 Oct 31;116(2):612–618. [PubMed]
  • Jackson WP, Islip PJ, Kneen G, Pugh A, Wates PJ. Acetohydroxamic acids as potent, selective, orally active 5-lipoxygenase inhibitors. J Med Chem. 1988 Mar;31(3):499–500. [PubMed]
  • Summers JB, Mazdiyasni H, Holms JH, Ratajczyk JD, Dyer RD, Carter GW. Hydroxamic acid inhibitors of 5-lipoxygenase. J Med Chem. 1987 Mar;30(3):574–580. [PubMed]
  • Veldink GA, Vliegenthart JF. Lipoxygenases, nonheme iron-containing enzymes. Adv Inorg Biochem. 1984;6:139–161. [PubMed]
  • Galpin JR, Tielens LG, Veldink GA, Vliegenthart JF, Boldingh J. On the interaction of some catechol derivatives with the iron atom of soybean lipoxygenase. FEBS Lett. 1976 Oct 15;69(1):179–182. [PubMed]
  • Clapp CH, Banerjee A, Rotenberg SA. Inhibition of soybean lipoxygenase 1 by N-alkylhydroxylamines. Biochemistry. 1985 Apr 9;24(8):1826–1830. [PubMed]
  • Kemal C, Louis-Flamberg P, Krupinski-Olsen R, Shorter AL. Reductive inactivation of soybean lipoxygenase 1 by catechols: a possible mechanism for regulation of lipoxygenase activity. Biochemistry. 1987 Nov 3;26(22):7064–7072. [PubMed]
  • Mansuy D, Cucurou C, Biatry B, Battioni JP. Soybean lipoxygenase-catalyzed oxidations by linoleic acid hydroperoxide: different reducing substrates and dehydrogenation of phenidone and BW 755C. Biochem Biophys Res Commun. 1988 Feb 29;151(1):339–346. [PubMed]
  • Kulkarni AP, Cook DC. Hydroperoxidase activity of lipoxygenase: a potential pathway for xenobiotic metabolism in the presence of linoleic acid. Res Commun Chem Pathol Pharmacol. 1988 Sep;61(3):305–314. [PubMed]
  • Rouzer CA, Samuelsson B. On the nature of the 5-lipoxygenase reaction in human leukocytes: enzyme purification and requirement for multiple stimulatory factors. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6040–6044. [PMC free article] [PubMed]
  • Ueda N, Kaneko S, Yoshimoto T, Yamamoto S. Purification of arachidonate 5-lipoxygenase from porcine leukocytes and its reactivity with hydroperoxyeicosatetraenoic acids. J Biol Chem. 1986 Jun 15;261(17):7982–7988. [PubMed]
  • Egan RW, Gale PH. Inhibition of mammalian 5-lipoxygenase by aromatic disulfides. J Biol Chem. 1985 Sep 25;260(21):11554–11559. [PubMed]
  • Rouzer CA, Samuelsson B. The importance of hydroperoxide activation for the detection and assay of mammalian 5-lipoxygenase. FEBS Lett. 1986 Aug 18;204(2):293–296. [PubMed]
  • Riendeau D, Denis D, Choo LY, Nathaniel DJ. Stimulation of 5-lipoxygenase activity under conditions which promote lipid peroxidation. Biochem J. 1989 Oct 15;263(2):565–572. [PMC free article] [PubMed]
  • Cashman JR, Lambert C, Sigal E. Inhibition of human leukocyte 5-lipoxygenase by 15-HPETE and related eicosanoids. Biochem Biophys Res Commun. 1988 Aug 30;155(1):38–44. [PubMed]
  • Reynolds CH. Inactivation of soybean lipoxygenase by lipoxygenase inhibitors in the presence of 15-hydroperoxyeicosatetraenoic acid. Biochem Pharmacol. 1988 Dec 1;37(23):4531–4537. [PubMed]
  • Riendeau D, Falgueyret JP, Nathaniel DJ, Rokach J, Ueda N, Yamamoto S. Sensitivity of immunoaffinity-purified porcine 5-lipoxygenase to inhibitors and activating lipid hydroperoxides. Biochem Pharmacol. 1989 Jul 15;38(14):2313–2321. [PubMed]
  • Belanger P, Maycock A, Guindon Y, Bach T, Dollob AL, Dufresne C, Ford-Hutchinson AW, Gale PH, Hopple S, Lau CK, et al. L-656,224 (7-chloro-2-[(4-methoxyphenyl)methyl]-3- methyl-5-propyl-4-benzofuranol): a novel, selective, orally active 5-lipoxygenase inhibitor. Can J Physiol Pharmacol. 1987 Dec;65(12):2441–2448. [PubMed]
  • Graff G, Anderson LA, Jaques LW. Preparation and purification of soybean lipoxygenase-derived unsaturated hydroperoxy and hydroxy fatty acids and determination of molar absorptivities of hydroxy fatty acids. Anal Biochem. 1990 Jul;188(1):38–47. [PubMed]
  • Verhagen J, Bouman AA, Vliegenthart JF, Boldingh J. Conversion of 9-D- and 13-L-hydroperoxylinoleic acids by soybean lipoxygenase-1 under anaerobic conditions. Biochim Biophys Acta. 1976 Jan 18;486(1):114–120. [PubMed]
  • Verhagen J, Veldink GA, Egmond MR, Vliegenthart JF, Boldingh J, van der Star J. Steady-state kinetics of the anaerobic reaction of soybean lipoxygenase-1 with linoleic acid and 13-L-hydroperoxylinoleic acid. Biochim Biophys Acta. 1978 Jun 23;529(3):369–379. [PubMed]
  • Van der Zee J, Eling TE, Mason RP. Formation of free radical metabolites in the reaction between soybean lipoxygenase and its inhibitors. An ESR study. Biochemistry. 1989 Oct 17;28(21):8363–8367. [PubMed]
  • Larsen IK, Sjöberg BM, Thelander L. Characterization of the active site of ribonucleotide reductase of Escherichia coli, bacteriophage T4 and mammalian cells by inhibition studies with hydroxyurea analogues. Eur J Biochem. 1982 Jun 15;125(1):75–81. [PubMed]
  • Lassmann G, Liermann B. ESR studies of structure and kinetics of radicals from hydroxyurea. An antitumor drug directed against ribonucleotide reductase. Free Radic Biol Med. 1989;6(3):241–244. [PubMed]
  • Gräslund A, Ehrenberg A, Thelander L. Characterization of the free radical of mammalian ribonucleotide reductase. J Biol Chem. 1982 May 25;257(10):5711–5715. [PubMed]

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