Conversion of leukotriene A4 to leukotriene B4: catalysis by human liver microsomes under anaerobic conditions

Details

• Personal Author:
  Goldman DW ; Gut J ; Jamieson GC ; Trudell JR
• Description:
  The presence of a microsomal enzyme that catalyzes leukotriene-A4 (LTA4) hydrolysis was demonstrated in human liver. The first application of the new technique of direct chemical ionization mass spectroscopy to the identification and characterization of underivatized leukotriene-B4 (LTB4) was also described. A 2 minute incubation of LTA4 with human liver microsomes allowed for the conversion of 1.7 mole percent to LTB4. Protein concentration, time, and substrate concentration were determining factors in this conversion. The conversion was not supported by heat inactivated microsomes nor did it require NADPH. Apparent Michaelis-Menten type behavior was determined through the kinetic analysis of the reaction. Among three patients examined, the production rates varied widely. LTB4 formation by microsomal LTA4 hydrolase was inhibited 52, 40, and 60 percent by piperonyl-butoxide, propanethiol, and cyclohexene-oxide, respectively. In the presence of 100 percent oxygen the activity of microsomal and cytosolic LTA4- hydrolase was decreased by 45 and 64 percent, respectively. The mass spectrum of 50 nanograms of underivatized synthetic LTB4 free acid was identical with that of 10 nanograms of the product isolated from LTA4 hydrolysis by human liver microsomes. [Description provided by NIOSH]
• Subjects:
  Enzymes Occupational Health Safety
• Keywords:
  Enzyme-activity Fatty-acids Grants-other In-vitro-studies Liver-microsomes Microsomal-enzymes NIOSH-Grant NIOSH-Publication
• ISSN:
  0003-9861
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  497-509
• Volume:
  259
• Issue:
  2
• NIOSHTIC Number:
  nn:00187002
• Citation:
  Arch Biochem Biophys 1987 Dec; 259(2):497-509
• Contact Point Address:
  Anesthesia Stanford University Department of Anesthesia Stanford, Calif 94305
• Federal Fiscal Year:
  1988
• NORA Priority Area:
  Other Occupational Concerns ; Grants Other
• Performing Organization:
  Stanford University, Stanford, California
• Peer Reviewed:
  True
• Start Date:
  19800901
• Source Full Name:
  Archives of Biochemistry and Biophysics
• End Date:
  19901130
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:62758928039ad0039b6c87be026c97c4c5f1cae57fad565db30106dfaf2ba3b98397f960da088ec7f8ed6cf2097bdff3e7c24df118fe4dc5fe2d06b3b99027e3
• Download URL:
  https://stacks.cdc.gov/view/cdc/204408/cdc_204408_DS1.pdf
• File Type:
  [PDF - 716.28 KB ]