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

Summary 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 () 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 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.