Interaction of Phthalates and Phenoxy Acid Herbicide Environmental Pollutants with Intestinal Intracellular Lipid Binding Proteins

Abstract

Transcellular diffusion across the columnar absorptive epithelial cells (enterocytes) of the small intestine is a major route of absorption for phthalate and phenoxy acid herbicide environmental pollutants that have been associated with adverse human health effects. The biochemical mechanisms responsible for the transport of these pollutants across the enterocyte, however, remain poorly characterized. In the present study, we have shown that the innate intestinal intracellular lipid binding proteins (iLBPs), namely, intestinal (I) and liver (L)-fatty acid binding proteins (FABP) bind to phthalate and phenoxy acid herbicides. The relative affinities of the compounds were determined by fluorescence competition assays, and a 3D-QSAR model was established for L-FABP. Structural information obtained from NMR chemical shift perturbation and molecular docking experiments defined the binding sites. Differential scanning calorimetry and proteolysis experiments revealed that the binding of these compounds produces stabilizing conformational changes in the structure of I-FABP. In summary, the presented biophysical data suggests that the binding of phthalate and phenoxy acid herbicides to intestinal iLBPs may increase the cytosolic solubility of these compounds and thereby may facilitate their transport from the intestinal lumen across the enterocyte to sites of distribution and metabolism.