Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions

Fatty acid binding proteins (FABP) form a family of proteins displaying tis sue-specific expression. These proteins are involved in fatty acid (FA) tra nsport and metabolism by mechanisms that also appear to be tissue-specific, Cellular retinoid binding proteins are related proteins with unknown roles in FA transport and metabolism. To better understand the origin of these t issue-specific differences we report new measurements, using the acrylodate d intestinal fatty acid binding protein (ADIFAB) method, of the binding of fatty acids (FA) to human fatty acid binding proteins (FABP) from brain, he art, intestine, liver, and myelin. We also measured binding of FA to a reti noic acid (CRABP-I) and a retinol (CRBP-II) binding protein and we have ext ended to 19 different FA our characterization of the FA-ADIFAB and FA-rat i ntestinal FABP interactions. These studies extend our previous analyses of human FABP from adipocyte and rat FABPs from heart, intestine, and liver. B inding affinities varied according to the order brain approximate to myelin approximate to heart > liver > intestine > CRABP > CRBP. In contrast to pr evious studies, no protein revealed a high degree of selectivity for partic ular FA. The results indicate that FA solubility (hydrophobicity) plays a m ajor role in governing binding affinities; affinities tend to increase with increasing hydrophobicity (decreasing solubility) of the FA. However, our results also reveal that, with the exception of the intestinal protein, FAB Ps exhibit an additional attractive interaction for unsaturated FA that par tially compensates for their trend toward lower affinities due to their hig her aqueous solubilities. Thermodynamic potentials were determined for olea te and arachidonate binding to a subset of the FABP and retinoid binding pr oteins. FA binding to all FABPs was enthalpically driven. The Delta H degre es values for paralogous FABPs, proteins from the same species but differen t tissues, reveal an exceptionally wide range of values, from -22 kcal/mol (myelin) to -7 kcal/mol (adipocyte). For orthologous FABPs from the same ti ssue but different species, Delta H degrees values were similar. In contras t to the enthalpic dominance of FA binding to FABP, binding of FA to CRABP- I was entropically driven, This is consistent with the notion that FA speci ficity for FABP is determined by the enthalpy of binding. Proteins from dif ferent tissues also revealed considerable heterogeneity in heat capacity ch anges upon FA binding, Delta C-p values ranged between 0 and -1.3 kcal mol( -1) K-1. The results demonstrate that thermodynamic parameters are quite di fferent for paralogous but are quite similar for orthologous FABP, suggesti ng tissue-specific differences in FABP function that may be conserved acros s species.