Fatty acid binding proteins stabilize leukotriene A4

Abstract

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.

Keywords

• half-life
• transcellular biosynthesis
• leukotriene biosynthesis