How do uncoupling proteins uncouple?

According to the proton buffering model, introduced by Klingenberg, UCP1 co nducts protons through a hydrophilic pathway lined with fatty acid head gro ups that buffer the protons as they move across the membrane. According to the fatty acid protonophore model, introduced by Garlid, UCPs do not conduc t protons at all. Rather, like all members of this gene family, they are an ion carriers. A variety of anions are transported, but the physiological su bstrates 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 prot onophores. Favoring the latter mechanism is the fact that the head group of long-chain alkylsulfonates, strong acid analogues of FA, is also transloca ted by UCP. (C) 2000 Elsevier Science B.V. All rights reserved.