Schnellmann R G, Manning R O
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602.
Biochim Biophys Acta. 1990 Apr 26;1016(3):344-8. doi: 10.1016/0005-2728(90)90167-3.
The effects of sulfluramide (N-ethylperfluorooctane sulfonamide) and perfluorooctane sulfonamide (DESFA) on isolated rabbit renal cortical mitochondria (RCM) were examined. Sulfluramid (1-100 microM) and DESFA (0.5-50 microM) increased state 4 respiration of RCM respiring on pyruvate/malate or succinate in a concentration dependent manner in the absence of a phosphate acceptor. In addition, both sulfluramid and DESFA increased state 4 respiration in the presence of oligomycin, an inhibitor of F0F1-ATPase. The effects of sulfluramid (200 microM), DESFA (100 microM), and the known protonophore and uncoupler of oxidative phosphorylation, carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) (1 microM), on RCM proton movement were examined directly by monitoring extramitochondrial pH and indirectly by monitoring passive mitochondrial swelling. Immediately upon addition, DESFA and FCCP, but not sulfluramid, dissipated the RCM proton gradient and caused RCM to swell in solutions of NaCl or NH4Cl. These results show that DESFA uncouples oxidative phosphorylation by acting as a protonophore. RCM were shown to metabolize sulfluramid to DESFA which suggests that the increase in state 4 respiration observed with sulfluramid is due to DESFA. DESFA is unique in that it is one of two uncouplers that does not contain a ring structure and thus may be a useful model in the study of oxidative phosphorylation.
研究了氟虫胺（N - 乙基全氟辛烷磺酰胺）和全氟辛烷磺酰胺（DESFA）对分离的兔肾皮质线粒体（RCM）的影响。在没有磷酸受体的情况下，氟虫胺（1 - 100微摩尔）和DESFA（0.5 - 50微摩尔）以浓度依赖的方式增加了RCM在丙酮酸/苹果酸或琥珀酸上呼吸的状态4呼吸。此外，氟虫胺和DESFA在存在F0F1 - ATP酶抑制剂寡霉素的情况下均增加了状态4呼吸。通过监测线粒体外pH直接以及通过监测被动线粒体肿胀间接研究了氟虫胺（200微摩尔）、DESFA（100微摩尔）和已知的氧化磷酸化质子载体和解偶联剂羰基氰化物对 - 三氟甲氧基苯基腙（FCCP）（1微摩尔）对RCM质子移动的影响。加入后，DESFA和FCCP立即消散了RCM质子梯度，并导致RCM在NaCl或NH4Cl溶液中肿胀，但氟虫胺没有此作用。这些结果表明DESFA通过作为质子载体使氧化磷酸化解偶联。研究表明RCM将氟虫胺代谢为DESFA，这表明用氟虫胺观察到的状态4呼吸增加是由于DESFA。DESFA的独特之处在于它是两种不含环结构的解偶联剂之一，因此可能是氧化磷酸化研究中的有用模型。
