Proton conductance caused by long-chain fatty acids in phospholipid bilayer membranes

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Abstract
Mechanisms of proton conductance (G H) were investigated in phospholipid bilayer membranes containing long-chain fatty acids (lauric, myristic, palmitic, oleic or phytanic). Membranes were formed from diphytanoyl phosphatidylcholine in decane plus chlorodecane (usually 30% vol/vol). Fatty acids were added either to the aqueous phase or to the membrane-forming solution. Proton conductance was calculated from the steadystate total conductance and the H+ diffusion potential produced by a transmembrane pH gradient. Fatty acids causedG H to increase in proportion to the first power of the fatty acid concentration. TheG H induced by fatty acids was inhibited by phloretin, low pH and serum albumin.G H was increased by chlorodecane, and the voltage dependence ofG H was superlinear. The results suggest that fatty acids act as simple (A− type) proton carriers. The membrane: water partition coefficient (K p ) and adsorption coefficient (β) were estimated by finding the membrane and aqueous fatty acid concentrations which gave identical values ofG H. For palmitic and oleic acidsK p was about 105 and β was about 10−2 cm. The A− translocation or “flip-flop” rate (k a ) was estimated from the value ofG H and the fatty acid concentration in the membrane, assuming that A− translocation was the rate limiting step in H+ transport. Thek A 's were about 10−4 sec−1, slower than classical weak-acid uncouplers by a factor of 105. Although long-chain fatty acids are relatively inefficient H+ carriers, they may cause significant biological H+ conductance when present in the membrane at high concentrations, e.g., in ischemia, hypoxia, hormonally induced lipolysis, or certain hereditary disorders, e.g., Refsum's (phytanic acid storage) disease.