The electrostatic contribution to binding in the choline transport system of erythrocytes.
Half-saturation constants have been determined for the choline carrier with cationic substrates and their uncharged carbon analogs: (a) choline and 3,3-dimethyl-1-butanol and (b) 2-dimethylaminoethanol and isoamyl alcohol. The constants are 6.3 microM and 16 mM for the first pair, and 19 microM and 45mM for the second. In both cases, the charged molecules have the higher affinity by a factor of more than 2000. This is to be compared with a factor of less than 10 for charged and neutral substrates of acetylcholinesterase, and with a similar factor in antigen-antibody reactions. To account for the unusually strong ionic bond, a very close association between the carrier site and the substrate is suggested, probably with exclusion of water of hydration. This is supported by the fact that gradual replacement of N-methyl groups in the substrate by N-ethyl groups sharply reduces affinity for the carrier with a 110-fold reduction overall, but has no significant effect on the enzymes.
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002091:Butyrylcholinesterase / Q000097:blood; D002417:Cattle; D002794:Choline / Q000097:blood*; D003642:Deanol / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism*; D000441:Hexanols / Q000494:pharmacology; D006736:Horses; D006801:Humans; D007700:Kinetics; D000439:Pentanols / Q000494:pharmacology; D011485:Protein Binding
D000441:Hexanols; D000439:Pentanols; D003642:Deanol; C007469:3,3-dimethylbutan-1-ol; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002794:Choline