Oxidation of 20-hydroxyleukotriene B4 to 20-carboxyleukotriene B4 by human neutrophil microsomes. Role of aldehyde dehydrogenase and leukotriene B4 ω-hydroxylase (cytochrome P-450(LTBω)) in leukotriene B4 ω-oxidation

H. Sumimoto, S. Minakami

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31 Citations (Scopus)


Leukotriene B4 (LTB4), a potent chemoattractant for leukocytes, is catabolized by human neutrophils via ω-oxidation. Neutrophil microsomes are known to oxidize 20-hydroxy-LTB4 (20-OH-LTB4) to its 20-oxo and 20-carboxy derivatives in the presence of NADPH. This activity has been ascribed to LTB4 ω-hydroxylase (cytochrome P-450(LTBω)), a conclusion supported by our finding of the reversal of carbon monoxide inhibition by 450 nm light and by competitive inhibition studies. The oxidation of 20-oxo-LTB4 to 20-carboxy-LTB4 is also catalyzed by microsomes fortified with 1 mM NAD+, and this activity is not affected by cytochrome P-450(LTBω) inhibitors. The evidence is compatible with involvement of a disulfiram-insensitive aldehyde dehydrogenase in this second oxidation pathway. Interaction of the two pathways is evidenced by facilitation of NADPH-dependent oxidation of 20-OH-LTB4 by the addition of NAD+. This synergism may be explained by removal of the aldehyde intermediate by the NAD+-dependent aldehyde dehydrogenase. Taken together with the finding that the NAD+-dependent activity is severalfold higher than the NADPH-dependent one, the dehydrogenase may be important in the oxidation of 20-OH-LTB4 to 20-carboxy-LTB4.

Original languageEnglish
Pages (from-to)4348-4353
Number of pages6
JournalJournal of Biological Chemistry
Issue number8
Publication statusPublished - 1990
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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