Determinants of intestinal mucosal uptake of short- and medium-chain fatty acids and alcohols

Uptake rates across the jejunal brush border have been measured for water-soluble fatty acids and alcohols and analyzed to determine the relative roles of the unstirred water layer and the lipid cell membrane as determinants of the intestinal absorptive process. Initial studies involving measurement of time courses of electrical transients developed across the intestine exposed to poorly permeant solute molecules showed no anomalous discrimination of probe molecules of different size or charge. This finding suggests that the diffusion barrier in the intestine can be considered as an unstirred water layer. Next, uptake rates of fatty acid were found to be linear with respect to concentration of the test solute, demonstrated no competitive inhibition or contralateral stimulation, had low temperature dependency, and were insensitive to metabolic inhibition, indicating that uptake proceeds by passive diffusion. Passive permeability coefficients, *P, varied from 22 i= 1.4 to 395 f 9.2 nmoles~min-l-lOO mg-l.m"l for the saturated fatty acids 2:O through 12:O and from 119 f 3.3 to 581 f 45.2 for the saturated alcohols 6:O through 1O:O. Vigorous stirring of the bulk buffer solution enhanced *P values in direct proportion to chain length while the presence of bile acid micelles depressed apparent permeability coefficients in proportion to fatty acid chain length. These results demonstrate that uptake of shortchain fatty acid monomers is rate limited by the lipid cell membrane but diffusion through the unstirred water layer becomes increasingly rate limiting Abbreviations: *P, apparent permeability coefficient; P, true Permeability coefficient corrected for unstirred layer effects; J d , experimentally determined flux rate with the units nmolesmin" 100 mg"; J , flux rate corrected for surface area of the unstirred layer with the units nmoles.sec" .ern+; D, free diffusion coefficient; d, thickness of the unstirred layer; S, effective surface area of the unstirred layer in an amount of intestine equivalent to 100 mg dry weight of tissue with the units cm2-100 mg"; CI, concentration of solute in the bulk perfusate; CZ, concentration of solute at the aqueous-lipid interface of the intestinal mucosa; Ca, concentration of solute just inside the mucosal cell membrane; M , molecular weight.