Monocarboxylic acid permeation through lipid bilayer membranes

Abstract

The membrane permeability coefficients for the homologous monocarboxylic acids, formic through hexanoic, as well as benzoic and salicylic, were determined for egg phosphatidylcholine-decane planar bilayer membranes. The permeabilities of formic, acetic and propionic acid were also determined for "solvent-free" phosphatidylethanolamine bilayers. Permeability coefficients were calculated from tracer fluxes measured under otherwise symmetrical conditions, and precautions were taken to ensure that the values were not underestimated due to unstirred layer effects. The relation between the nonionic (HA) permeability (Pm) and the hexadecane/water partition coefficient (Kp) was: log Pm = 0.90 log Kp + 0.87 (correlation coefficient = 0.996). Formic acid was excluded from the analysis because its permeability was sixfold higher than predicted by the other acids. The permeabilities for "solvent-free" membranes were similar to those for decane-containing membranes. The exceptionally high permeability of formic acid and the high correlation of the other permeabilities to the hexadecane/water partition coefficient is a pattern that conforms with other nonelectrolyte permeabilities through bilayers. Similarly, the mean incremental free energy change per methylene group (delta delta G/-CH2-) was -764 cal mol-1, similar to other homologous solutes in other membrane systems. However, much less negative delta delta G values (-120 to -400 cal mol-1) were previously reported for fatty acids permeating bilayers and biological membranes. These values are due primarily to unstirred layer effects, metabolism and binding to membranes and other cell components.

110 Years of the Meyer–Overton Rule: Predicting Membrane Permeability of Gases and Other Small Compounds

“…[30] This finding violates the Meyer-Overton rule in two respects: i) P M,SA is unreasonably low. From the octanol water partition coefficient K p ≈300, [31] Equation (1) (3) that is, the difference between P M,SA− and P M,SA should be three orders of magnitude larger than has been reported. [30] The reason for the discrepancy between theory and experiment becomes evident, if the limitations of the experimental approach are considered.…”

“…In perfect agreement with the Meyer-Overton rule, the same authors found 1.1 cm s −1 for hexanoic acid. [31] It is thus safe to conclude that the study by Grime et al [39,42] was hampered by UL effects. UL limitations led to severe underestimations of P M for all carboxylic acids in their system.…”

An Na(+)-independent short-chain fatty acid transporter contributes to intracellular pH regulation in murine colonocytes.

“…This implies that at the prevailing pH values of the colonic lumen (pH 6-7.5; Cummings et al, 1987), at least 90% of all SCFAs exist in the ionized (anionic) form. Despite a relative abundance of the anionic form, it is difficult to predict whether the transmembrane fluxes of any one molecular form will predominate because nonionic diffusion is extremely rapid across many artificial and cellular membranes (Roos and Boron, 1981;Walter and Gutknecht, 1984;Montrose and Kimmich, 1986).…”

Quantitative visualization of passive transport across bilayer lipid membranes

“…On the other hand, some weak acid protonophores may also exert detrimental effects on cellular processes such as oxidative phosphorylation, apoptosis (7), and photosynthesis (8). The transport of weak acids across model cell membranes and the determination of permeation rates have consequently been the subject of a considerable number of studies (9)(10)(11)(12)(13)(14)(15)(16)(17)). …”