A STRUCTURE-ACTIVITY STUDY OF FATTY-ACID INTERACTION WITH MITOCHONDRIAL UNCOUPLING PROTEIN

Fatty acid (FA) uniport via mitochondrial uncoupling protein (UcP) was detected fluorometrically with PBFI, potassium-binding benzofuran pht halate and SPQ, 6-methoxy-N-(3-sulfopropyl)-quinolinium, indicating K and H+, respectively, The FA structural patterns required for FA flip -flop, UcP-mediated FA uniport, activation of UcP-mediated H+ transpor t in proteoliposomes, and inhibition of UcP-mediated Cl- uniport by FA , were identical. Positive responses were found exclusively with FA wh ich were able to flip-flop in a protonated form across the membrane an d no responses were found with 'inactive' FA lacking the flip-flop abi lity. The findings support the existence of FA cycling mechanism. (C) 1997 Federation of European Biochemical Societies.