Diffusion of Weak Acids across Lipid Bilayer Membranes: Effects of Chemical Reactions in the Unstirred Layers

Chemical reactions in the aqueous unstirred layers of solution adjacent to a membrane can have dramatic effects on the diffusion of solutes across that membrane. This is demonstrated by the diffusion of labeled salicylate and salicylic acid across a phospholipid bilayer membrane. Two types of chemical reactions are considered. The first is an isotopic exchange reaction between the ionic and nonionic forms of a weak acid, HA + *A(-) [unknown] H*A + A(-). This reaction provides a way of estimating the true membrane permeability to a highly permeant weak acid and also a way of estimating the thickness of the unstirred layers. The second chemical reaction, the dissociation of a weak acid, HA [unknown] H(+) + A(-), can be used to show how the presence or absence of buffers in the unstirred layers controls the net transport of permeant weak acids across a membrane. In principle, the addition of appropriate "antacid" buffers to salicylates can increase their rate of absorption from the stomach.