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Properties of Enzymes in Hepatocytes That Convert 5-HPETE or LTA4 into LTB4



Details

  • Personal Author:
  • Description:
    Rat hepatocyte homogenates convert 5-hydroperoxyeicosatetraenoic acid (5-HPETE) into biologically active leukotriene B4 (LTB4) as well as less active all-trans-LTB4 (i.e., 6-trans-LTB4 and 6-trans-12-epi-LTB4). Here, we present a hypothesis of the reaction mechanism and the minimal structural requirements of the active enzyme based on the following experimental evidence: The ED50 of the inhibitors 5,8,11,14-eicosatetraynoic acid (ETYA) and 5,6-dehydro-eicosatetraenoic acid was approximately 100-fold higher than for 5-lipoxygenase. Propanethiol and O2 were strong inhibitors of LTB4 formation, whereas butylated hydroxytoluene, nordihydroguaiaretic acid, metyrapone, Desferal and CO had no effect. Cytochrome c, catalase, hematin, and a Fe3+/Fe2+ couple, but not iron-free protoporphyrin IX, catalyzed the formation of only all-trans-LTB4. LTB4 formation in hepatocyte homogenates was heat- and trypsin-sensitive whereas all-trans-LTB4 formation was not. We propose that a ferric heme iron forms a ferryl-hydroxo complex upon homolytic scission of the oxygen-oxygen bond in 5-HPETE and the resulting 5,6-trans-epoxide radical is oxidized by the ferryl-hydroxo complex to yield LTA4. A mechanism for hydrolysis of LTA4 is described that results in formation of LTB4 (<1% yield) rather than all-trans-LTB4. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    0891-5849
  • Document Type:
    Text
  • Funding:
    Grant
  • Genre:
    Journal Article
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Pages in Document:
    275-284
  • Volume:
    7
  • Issue:
    3
  • NIOSHTIC Number:
    nn:20060069
  • Citation:
    Free Radic Biol Med 1989 Sep; 7(3):275-284
  • Contact Point Address:
    J.R. Trudell, Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305-5117, U.S.A.
  • Federal Fiscal Year:
    1989
  • Performing Organization:
    Stanford University, Stanford, California
  • Peer Reviewed:
    True
  • Start Date:
    19800901
  • Source Full Name:
    Free Radical Biology and Medicine
  • End Date:
    19901130
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:ad70674b311dd6001867bb0e4295b66a3ab73e7eb855e254acde738cc863c005d63c21884e0399d8c68306d3984291f6e8b2f31ca8cb0e1b8e363572698f8b8a
  • Download URL:
  • File Type:
    Filetype[PDF - 895.18 KB ]
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