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Journal of Lipid Research, Vol. 45, 2138-2144, November 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Fatty acid binding proteins stabilize leukotriene A₄

Jennifer S. Dickinson Zimmer^*,, Douglas F. Dyckes, David A. Bernlohr^** and Robert C. Murphy^1,*,

^* Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206
Department of Chemistry, University of Colorado at Denver, Denver, CO 80217
^** Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455

¹ To whom correspondence should be addressed. e-mail: robert.murphy{at}uchsc.edu

Leukotriene A₄ (LTA₄) is a chemically reactive conjugated triene epoxide product derived from 5-lipoxygenase oxygenation of arachidonic acid. At physiological pH, this reactive compound has a half-life of less than 3 s at 37°C and 40 s at 4°C. Regardless of this aqueous instability, LTA₄ is an intermediate in the formation of biologically active leukotrienes, which can be formed through either intracellular or transcellular biosynthesis. Previously, epithelial fatty acid binding protein (E-FABP) present in RBL-1 cells was shown to increase the half-life of LTA₄ to 20 min at 4°C. Five FABPs (adipocyte FABP, intestinal FABP, E-FABP, heart/muscle FABP, and liver FABP) have now been examined and also found to increase the half-life of LTA₄ at 4°C to 20 min with protein present. Stabilization of LTA₄ was examined when arachidonic acid was present to compete with LTA₄ for the binding site on E-FABP. Arachidonate has an apparent higher affinity for E-FABP than LTA₄ and was able to completely block stabilization of the latter. When E-FABP is not saturated with arachidonate, FABP can still stabilize LTA₄.

Several lipoxygenase products, including 5-hydroxyeicosatetraenoic acid, 5,6-dihydroxyeicosatetraenoic acid, and leukotriene B₄, were found to have no effect on the stability of LTA₄ induced by E-FABP even when present at concentrations 3-fold higher than LTA₄.

Abbreviations: cPLA₂, cytosolic phospholipase A₂; diHETE, dihydroxyeicosatetraenoic acid; EET, epoxyeicosatrienoic acid; FABP, fatty acid binding protein; FLAP, 5-lipoxygenase-activating protein; HETE, hydroxyeicosatetraenoic acid; HpETE, hydroperoxyeicosatetraenoic acid; LTA₄, leukotriene A₄; LTB₄, leukotriene B₄; TEA, triethylamine; 5-LO, 5-lipoxygenase

Supplementary key words half-life • transcellular biosynthesis • leukotriene biosynthesis

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