Open AccessThe ω‐hydroxylation of arachidonic acid by human polymorphonuclear leukocytes
Author(s) -
HATZELMANN Armin,
ULLRICH Volker
Publication year - 1988
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1988.tb14019.x
Subject(s) - arachidonic acid , monooxygenase , hydroxylation , metabolite , chemistry , cytochrome p450 , microsome , biochemistry , granulocyte , hydroxyeicosatetraenoic acid , stereochemistry , metabolism , enzyme , biology , immunology
Incubations of [1‐ 14 C]arachidonic acid with unstimulated human polymorphonuclear leukocytes resulted in the formation of four new metabolites in a previously described reverse‐phase HPLC system. Three of these metabolites were largely suppressed in a CO/O 2 (80/20, by vol.) atmosphere indicating a cytochrome‐ P 450‐dependent monooxygenase reaction. In agreement with this assumption is their NADPH/O 2 ‐dependent formation in the microsomal fraction. One metabolite was identified by gas chromatography/mass spectrometry analysis as ω‐hydroxy‐arachidonic acid and the two others were secondary products identified as ω‐carboxy‐arachidonic acid and 5,20‐dihydroxy‐ E,Z,Z,Z ‐6,8,11,14‐eicosatetraenoic acid. Since the affinity for arachidonate of the ω‐monooxygenase was quite low and the presence of LTB 4 suppressed the ω‐hydroxylation of arachidonate, we conclude that the known LTB 4 ω‐monooxygenase is responsible for the formation of ω‐hydroxy‐arachidonate. It is unlikely, however, that significant concentrations of these metabolites are formed by activated polymorphonuclear leukocytes in vivo. The fourth metabolite remains tightly associated with the leukocytes but has not been further characterized.