Jezek P, Garlid K D
Department of Pharmacology, Medical College of Ohio, Toledo 43699.
J Biol Chem. 1990 Nov 5;265(31):19303-11.
A large number of new substrates for anion uniport by the uncoupling protein of brown adipose tissue mitochondria have been found. These include alkylsulfonates, alkylsulfates and their derivatives, benzenesulfonate, oxohalogenides, hypophosphate, hexafluorophosphate, and pyruvate. Although the spectrum of anion selectivity is far wider than had previously been suspected, there are strong structural requirements for transport. The anion must be monovalent, and polar groups must not be attached to alkyl or aryl chains. The most striking finding is that transport increases dramatically with anion hydrophobicity. Anions that are transported are shown to compete with Cl- for transport by the reconstituted uncoupling protein. For each anion, the Ki for GDP inhibition of transport increases with its rate of transport and correlates inversely with its Ki for competitive inhibition of Cl- transport. For alkylsulfonates, transport rate, Ki for GDP inhibition, and Ki for inhibition of Cl- transport each depend monotonically on alkyl chain length. These findings suggest several new hypotheses relating to the molecular mechanism of transport through uncoupling protein and suggest explanations for observed functional differences among porters belonging to the same gene family.
已发现大量可被棕色脂肪组织线粒体解偶联蛋白用于阴离子单向转运的新底物。这些底物包括烷基磺酸盐、烷基硫酸盐及其衍生物、苯磺酸盐、卤氧化物、次磷酸盐、六氟磷酸盐和丙酮酸。尽管阴离子选择性的范围比之前怀疑的要宽得多，但转运存在严格的结构要求。阴离子必须是单价的，极性基团不能连接到烷基或芳基链上。最显著的发现是，转运随着阴离子疏水性的增加而急剧增加。被转运的阴离子被证明可与氯离子竞争通过重组解偶联蛋白的转运。对于每种阴离子，GDP对转运抑制的Ki值随其转运速率增加，且与其对氯离子转运竞争性抑制的Ki值呈负相关。对于烷基磺酸盐，转运速率、GDP抑制的Ki值以及氯离子转运抑制的Ki值均单调依赖于烷基链长度。这些发现提出了几个与通过解偶联蛋白进行转运的分子机制相关的新假说，并为属于同一基因家族的转运体中观察到的功能差异提供了解释。
