Jabůrek M, Varecha M, Gimeno R E, Dembski M, Jezek P, Zhang M, Burn P, Tartaglia L A, Garlid K D
Department of Biochemistry and Molecular Biology, Oregon Graduate Institute of Science and Technology, Beaverton, Oregon 97006-8921, USA.
J Biol Chem. 1999 Sep 10;274(37):26003-7. doi: 10.1074/jbc.274.37.26003.
Uncoupling protein 1 (UCP1) dissipates energy and generates heat by catalyzing back-flux of protons into the mitochondrial matrix, probably by a fatty acid cycling mechanism. If the newly discovered UCP2 and UCP3 function similarly, they will enhance peripheral energy expenditure and are potential molecular targets for the treatment of obesity. We expressed UCP2 and UCP3 in Escherichia coli and reconstituted the detergent-extracted proteins into liposomes. Ion flux studies show that purified UCP2 and UCP3 behave identically to UCP1. They catalyze electrophoretic flux of protons and alkylsulfonates, and proton flux exhibits an obligatory requirement for fatty acids. Proton flux is inhibited by purine nucleotides but with much lower affinity than observed with UCP1. These findings are consistent with the hypothesis that UCP2 and UCP3 behave as uncoupling proteins in the cell.
解偶联蛋白1（UCP1）通过催化质子回流到线粒体基质中消耗能量并产生热量，可能是通过脂肪酸循环机制。如果新发现的UCP2和UCP3功能相似，它们将增加外周能量消耗，并且是治疗肥胖症的潜在分子靶点。我们在大肠杆菌中表达了UCP2和UCP3，并将去污剂提取的蛋白质重新组装到脂质体中。离子通量研究表明，纯化的UCP2和UCP3的行为与UCP1相同。它们催化质子和烷基磺酸盐的电泳通量，并且质子通量对脂肪酸有强制性需求。嘌呤核苷酸可抑制质子通量，但亲和力比UCP1低得多。这些发现与UCP2和UCP3在细胞中作为解偶联蛋白发挥作用的假设一致。
