PMID- 15342681 OWN - NLM STAT- MEDLINE DCOM- 20050421 LR - 20210217 IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 45 IP - 11 DP - 2004 Nov TI - Fatty acid binding proteins stabilize leukotriene A4: competition with arachidonic acid but not other lipoxygenase products. PG - 2138-44 AB - Leukotriene A(4) (LTA(4)) 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 degrees C and approximately 40 s at 4 degrees C. Regardless of this aqueous instability, LTA(4) 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 LTA(4) to approximately 20 min at 4 degrees 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 LTA(4) at 4 degrees C to approximately 20 min with protein present. Stabilization of LTA(4) was examined when arachidonic acid was present to compete with LTA(4) for the binding site on E-FABP. Arachidonate has an apparent higher affinity for E-FABP than LTA(4) and was able to completely block stabilization of the latter. When E-FABP is not saturated with arachidonate, FABP can still stabilize LTA(4). Several lipoxygenase products, including 5-hydroxyeicosatetraenoic acid, 5,6-dihydroxyeicosatetraenoic acid, and leukotriene B(4), were found to have no effect on the stability of LTA(4) induced by E-FABP even when present at concentrations 3-fold higher than LTA(4). FAU - Zimmer, Jennifer S Dickinson AU - Zimmer JS AD - Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA. FAU - Dyckes, Douglas F AU - Dyckes DF FAU - Bernlohr, David A AU - Bernlohr DA FAU - Murphy, Robert C AU - Murphy RC LA - eng GR - GM-07635/GM/NIGMS NIH HHS/United States GR - HL-25785/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. DEP - 20040901 PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Carrier Proteins) RN - 0 (Fatty Acid-Binding Proteins) RN - 0 (Hydroxyeicosatetraenoic Acids) RN - 0 (Leukotriene A4) RN - 27YG812J1I (Arachidonic Acid) RN - 467RNW8T91 (5-hydroxy-6,8,11,14-eicosatetraenoic acid) RN - 71651-85-9 (5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid) RN - EC 1.13.11.12 (Lipoxygenase) SB - IM MH - Animals MH - Arachidonic Acid/*metabolism MH - Binding Sites MH - Binding, Competitive MH - Biochemical Phenomena MH - Biochemistry MH - Carrier Proteins/*physiology MH - Cell Line MH - Dose-Response Relationship, Drug MH - Fatty Acid-Binding Proteins MH - Hydrogen-Ion Concentration MH - Hydroxyeicosatetraenoic Acids/pharmacology MH - Leukotriene A4/chemistry/*metabolism MH - Lipoxygenase/*metabolism MH - Mass Spectrometry MH - Models, Biological MH - Protein Binding MH - Rats MH - Temperature MH - Time Factors EDAT- 2004/09/03 05:00 MHDA- 2005/04/22 09:00 CRDT- 2004/09/03 05:00 PHST- 2004/09/03 05:00 [pubmed] PHST- 2005/04/22 09:00 [medline] PHST- 2004/09/03 05:00 [entrez] AID - S0022-2275(20)34145-6 [pii] AID - 10.1194/jlr.M400240-JLR200 [doi] PST - ppublish SO - J Lipid Res. 2004 Nov;45(11):2138-44. doi: 10.1194/jlr.M400240-JLR200. Epub 2004 Sep 1.