title: How do uncoupling proteins uncouple?
abstract: According to the proton buffering model, introduced by Klingenberg, UCP1 conducts protons through a hydrophilic pathway lined with fatty acid head groups that buffer the protons as they move across the membrane. According to the fatty acid protonophore model, introduced by Garlid, UCPs do not conduct protons at all. Rather, like all members of this gene family, they are anion carriers. A variety of anions are transported, but the physiological substrates are fatty acid (FA) anions. Because the carboxylate head group is translocated by UCP, and because the protonated FA rapidly diffuses across the membrane, this mechanism permits FA to behave as regulated cycling protonophores. Favoring the latter mechanism is the fact that the head group of long-chain alkylsulfonates, strong acid analogues of FA, is also translocated by UCP.
authors.affiliation: Department of Biochemistry and Molecular Biology, Oregon Graduate Institute of Science and Technology, Beaverton 97006, USA. garlid@bmb.ogi.edu
authors.forename: K D
authors.initials: KD
authors.lastname: Garlid
authors.forename: M
authors.initials: M
authors.lastname: Jabůrek
authors.forename: P
authors.initials: P
authors.lastname: Jezek
authors.forename: M
authors.initials: M
authors.lastname: Varecha
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins; D000838:Anions; D001692:Biological Transport; D002021:Buffers; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D007473:Ion Channels; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D008956:Models, Chemical; D011506:Proteins / Q000378:metabolism; D011522:Protons; D014475:Uncoupling Agents / Q000378:metabolism*; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
chemical_list: D027321:Anion Transport Proteins; D000838:Anions; D002021:Buffers; D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D011522:Protons; C000604371:UCP1 protein, human; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3