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 phthalate 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+ transport in proteoliposomes, and inhibition of UcP-mediated Cl- uniport by FA, were identical. Positive responses were found exclusively with FA which were able to flip-flop in a protonated form across the membrane and no responses were found with 'inactive' FA lacking the flip-flop ability. The findings support the existence of FA cycling mechanism.
Jezek
P
P
Institute of Physiology, Department of Membrane Transport Biophysics, Academy of Sciences of the Czech Republic, Prague. jezek@sun1.biomed.cas.cz
Modrianský
M
M
Garlid
K D
KD
D001565:Benzoates / Q000378:metabolism; D001572:Benzofurans / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D004988:Ethers, Cyclic / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D005470:Fluorometry; D006153:Guanosine Diphosphate / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels; D007476:Ionophores / Q000494:pharmacology; D007850:Lauric Acids / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D024101:Mitochondrial Proteins; D011188:Potassium / Q000378:metabolism; D011485:Protein Binding; D011522:Protons; D011806:Quinolinium Compounds / Q000378:metabolism; D013329:Structure-Activity Relationship; D000071256:Uncoupling Protein 1; D014634:Valinomycin / Q000494:pharmacology
D001565:Benzoates; D001572:Benzofurans; D002352:Carrier Proteins; D002712:Chlorides; D004988:Ethers, Cyclic; D005227:Fatty Acids; D005456:Fluorescent Dyes; D007473:Ion Channels; D007476:Ionophores; D007850:Lauric Acids; D008081:Liposomes; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011522:Protons; D011806:Quinolinium Compounds; D000071256:Uncoupling Protein 1; C073886:potassium-binding benzofuran isophthalate; D006153:Guanosine Diphosphate; D014634:Valinomycin; C031263:12-hydroxydodecanoic acid; C052335:6-methoxy-N-(3-sulfopropyl)quinolinium; D011188:Potassium