Ionophoric Properties of 1,3-Bis[4-(trifluoromethyl)phenyl]urea on Bilayer Lipid Membranes in the Absence of Fatty Acids.

内容摘要

Diaryl ureas and thioureas have long been known to uncouple oxidative phosphorylation in isolated mitochondria and cells. However, the mechanism of this action remains poorly understood. The prevailing current view is that substituted diaryl ureas can increase the proton conductance of lipid membranes by forming complexes with fatty acids. For 1,3-bis[4-(trifluoromethyl)phenyl]urea (TFMP-urea), we showed that this substituted diphenylurea, in the absence of fatty acids at neutral pH, accelerated proton transport and H+/Cl- symport on planar bilayer lipid membranes (BLMs) and liposomes loaded with the fluorescent pH-sensitive probe 8-hydroxypyrene-1,3,6-trisulfonic acid. The protonophoric action of TFMP-urea proceeded via translocation of neutral protonated form and anionic deprotonated form through the membrane. The presence of palmitic acid in the lipid mixture led to a several-fold increase in the BLM current mediated by TFMP-urea and an improvement in its proton selectivity. We also showed that bovine serum albumin reduced the BLM current mediated by TFMP-urea due to its ability to bind this compound.