Wojtczak L, Wieckowski M R
Nencki Institute of Experimental Biology, Warsaw, Poland.
J Bioenerg Biomembr. 1999 Oct;31(5):447-55. doi: 10.1023/a:1005444322823.
Nonesterified long-chain fatty acids have long been known as uncouplers of oxidative phosphorylation. They are efficient protonophores in the inner mitochondrial membrane but not so in artificial phospholipid membranes. In the un-ionized form, they undergo a rapid spontaneous transbilayer movement (flip-flop). However, the transbilayer passage of the dissociated (anionic) form is hindered by the negatively charged hydrophilic carboxylic group. In the inner mitochondrial membrane, the transfer of fatty acid anions is mediated by the adenine nucleotide translocase, the dicarboxylate carrier, and the glutamate/aspartate carrier. As a result, the passage of protons and electric charges is a concerted effect of the spontaneous flip-flop of the undissociated (protonated) form in one direction and carrier-facilitated transfer of the ionized (deprotonated) form in the other direction. In addition, fatty acids also promote opening of the mitochondrial permeability transition pore, presumably due to their interaction with one of its constituents, the adenine nucleotide translocase, thus forming an additional route for dissipation of the proton gradient. Structural prerequisites for these proton-conducting mechanisms are (1) a weakly ionized carboxylic group and (2) a hydrocarbon chain of appropriate length without substituents limiting its mobility and hydrophobicity.
非酯化长链脂肪酸长期以来一直被认为是氧化磷酸化的解偶联剂。它们是线粒体内膜中高效的质子载体，但在人工磷脂膜中则不然。以非离子形式存在时，它们会快速自发地进行跨膜运动（翻转）。然而，解离（阴离子）形式的跨膜通道会受到带负电荷的亲水性羧基的阻碍。在线粒体内膜中，脂肪酸阴离子的转运由腺嘌呤核苷酸转位酶、二羧酸载体和谷氨酸/天冬氨酸载体介导。因此，质子和电荷的通过是未解离（质子化）形式在一个方向上的自发翻转与离子化（去质子化）形式在另一个方向上的载体促进转运的协同效应。此外，脂肪酸还可能由于其与线粒体通透性转换孔的一种成分腺嘌呤核苷酸转位酶相互作用，从而促进该孔的开放，进而形成质子梯度消散的另一条途径。这些质子传导机制的结构前提是：（1）一个弱电离的羧基；（2）一条长度合适且没有取代基限制其流动性和疏水性的烃链。
