Effect of a phenyl group in quaternary ammonium compounds on thiamine uptake in isolated rat hepatocytes.
The inhibitory effect of a phenyl group in quaternary ammonium compounds on thiamine uptake in isolated rat hepatocytes was investigated. The phenyltrimethylammonium ion was a more potent inhibitor than the tetramethylammonium ion, while the dibenzyldimethylammonium ion was the most potent inhibitor of thiamine uptake among those compounds examined. A kinetic study showed that this compound was a competitive inhibitor. The cetyltrimethylammonium ion was a less effective inhibitor than the benzyltrimethylammonium ion, and the palmitoylcholine ion was a weak inhibitor. These results indicate that the lipophilicity of a quaternary ammonium compound is not always correlated with its affinity for thiamine-carrier binding, but the presence of a phenyl group plays a significant role in affinity. The inhibitory effect of the series of (CH3)3N+ (CH2)nC6H5 (n = 0-6) compounds on thiamine uptake in isolated rat hepatocytes was studied. The maximal inhibitory activity occurred at n = 5. These results suggest that the phenyl group in a quaternary ammonium compound has a specific interaction with the thiamine-binding site in rat liver plasma membrane.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013831:Thiamine / Q000378:metabolism*
D000644:Quaternary Ammonium Compounds; D013831:Thiamine