title: Very long chain n-3 and n-6 polyunsaturated fatty acids bind strongly to liver fatty acid-binding protein.
abstract: Synthesis of n-3 and n-6 very long chain-PUFAs (VLC-PUFAs) from 18-carbon essential fatty acids is differentially regulated. The predominant product arising from n-3 fatty acids is docosahexaenoic acid (22:6n-3), with the liver serving as the main site of production. The synthetic pathway requires movement of a 24-carbon intermediate from the endoplasmic reticulum to peroxisomes for retroconversion to 22:6n-3. The mechanism of this intra-organelle flux is unknown, but could be binding-protein facilitated. We thus investigated binding of a series of previously untested VLC-PUFAs to liver fatty acid-binding protein (L-FABP). Three fluorometric assays were employed, all of which showed strong binding (K(d)' approximately 10(-8) to 10(-7) M) of 20-, 22-, and 24-carbon n-3 PUFAs to L-FABP. In contrast, synthesis of the predominant n-6 PUFA product, arachidonic acid, does not require intra-organelle transport. However, we found that n-6 VLC-PUFAs bound to L-FABP with affinities (K(d)' approximately 10(-8) to 10(-7) M) comparable to their n-3 counterparts. Although these results raise the possibility that L-FABP may participate in the cytoplasmic processing of n-3 and n-6 VLC-PUFAs, there is no evidence on the basis of binding affinities that L-FABP accounts for differences in the predominant products formed by the n-3 and n-6 PUFA metabolic pathways.
authors.affiliation: Department of Pediatrics, University of Iowa College of Medicine, Iowa City, IA 52242, USA. andrew.norris@joslin.harvard.edu
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Norris
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Spector
mesh_terms: D000817:Anilino Naphthalenesulfonates / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D003619:Dansyl Compounds / Q000032:analysis / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D051381:Rats
chemical_list: D000817:Anilino Naphthalenesulfonates; D002352:Carrier Proteins; D003619:Dansyl Compounds; C493320:Fabp1 protein, mouse; C493321:Fabp1 protein, rat; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D005456:Fluorescent Dyes; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C027132:1-anilino-8-naphthalenesulfonate; C054400:11-(dansylamino)undecanoic acid