Convergent oxygenation of arachidonic acid by 5-lipoxygenase and cyclooxygenase-2.
5-Lipoxygenase and cyclooxygenase-2 (COX-2) initiate the biosynthesis of distinct families of mediators from arachidonic acid (leukotrienes and prostaglandins, respectively) and are each the target of anti-inflammatory medications. Here we show that the product of 5-lipoxygenase, 5S-hydroxyeicosatetraenoic acid, is selectively and efficiently triply oxygenated by COX-2, implicating a cross-pathway interaction. The product is a unique diendoperoxide, potentially representing the parent compound of a novel group of lipid mediators.
Schneider
Claus
C
Department of Pharmacology, Division of Clinical Pharmacology, 23rd Avenue South at Pierce, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA. claus.schneider@vanderbilt.edu
Boeglin
William E
WE
Yin
Huiyong
H
Stec
Donald F
DF
Voehler
Markus
M
D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry / Q000378:metabolism*; D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction
D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2