Transport of Organic Compounds through Biological Membranes. II. Red Cell Permeability to O-Acyl-S-benzoylthiamines

抄録

The cell permeability was compared for a series of O-acyl-S-benzoylthiamine in human red cell suspensions. On varying the length of straight chain alkyl group in the acyl part, it was found that i) at the earliest stage of the transport, the red cells showed a rapid and high uptake of the molecules due to the adsorption at the cell membranes, and ii) an equilibrium state was reached within 120 minutes of incubation and the intracellular concentration of total thiamine was in the following order : acetate<propionate<butyrate>valerate>caproate>capryrate, showing a maximum intracellular accumulation (the cell to medium concentration ratio of 2.9) with 4 carbon acyl group. In order to elucidate the mechanism, the followings were compared for the series of compounds : i) the partition coefficient from aqueous to organic phases, ii) the rate of debenzoylation in the cells and at the membrane site, and iii) the rate of conversion of the corresponding O-acylthiamine to thiamine in the cells and at the membrane site. The results indicated that the hydrolytic enzyme systems associated with the cell membrane (acetylcholinesterase) and the cytoplasm (carboxylesterase) play the most important role in determining the intracellular accumulation rather than the lipid solubility of the compound and that the butyrate with the highest rate of conversion to thiamine in the cells results in the highest intracellular accumulation.