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Substrate specificity of the intestinal brush-border proline/sodium (IMINO) transporter

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Summary

l-proline uptake via the intestinal brush-borderIMINO carrier was tested for inhibition by 41 compounds which included sugars, N-methylated, α-,β-, γ- and ε-amino and imino acids, and heterocyclic analogs of pyrrolidine, piperidine and pyridine. Based on competitive inhibitor constants (apparentK/'s) we find that theIMINO carrier binding site interacts with molecules which possess a well-defined set of structural prerequisites. The ideal inhibitor must 1) be a heterocyclic nitrogen ring, 2) have a hydrophobic region, 3) be thel-stereoisomer of 4) an electronegative carbonyl group which is 5) separated by a one-carbon atom spacer from 6) an electropositive tetrahedral imino nitrogen with two H atoms. Finally, 7) the inhibitor conformation determined by dynamic ring puckering must position all these features within a critical domain. The two best inhibitors arel-pipecolate (apparentK/0.2mm) andl-proline (apparentK/0.3mm).

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  1. Bruce R. Stevens

    Present address: Department of Physiology, College of Medicine, University of Florida, Box J-274, 32610, Gainesville, Fla

Authors and Affiliations

  1. Department of Physiology, School of Medicine, University of California Medical Center, 90024, Los Angeles, California

    Bruce R. Stevens & Ernest M. Wright

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  1. Bruce R. Stevens
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Stevens, B.R., Wright, E.M. Substrate specificity of the intestinal brush-border proline/sodium (IMINO) transporter. J. Membrain Biol. 87, 27–34 (1985). https://doi.org/10.1007/BF01870696

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  • DOI: https://doi.org/10.1007/BF01870696

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