Transport of the Four Isomers of 2-Aminonorbornane-2-carboxylic Acid in Selected Mammalian Systems and in Escherichia coli

We have investigated, with the use of the four isomers of 2-aminonorbornane-2-carboxylic acid, the stereochemical specificity shown by several cell types for transporting amino acids with large, apolar side chains. The degree of specificity observed varied from low to high. The isomer of the model amino acid with carboxyl group exo and with configuration 1S was excreted by the rat more rapidly than its optical antipode, whereas the distribution of the two isomers in eight tissues of that animal was nearly the same. Although the kinetic constants for the uptake of the racemic, geometric isomers in the Ehrlich ascites tumor cell were different, the latter two enantiomorphs seemed to be transported by the same route. The hamster small intestine took up the two geometric isomers at similar rates, whereas both rates and inhibitory profiles for the two carboxyl-exo isomers showed that they were not taken up extensively by the same system. These two isomers were, however, absorbed from the gut at similar rates in the intact hamster. Only the isomer with carboxyl group exo and with configuration 1R was transported by Escherichia coli K-12, the same isomer being by far the most strongly bound to a binding protein for amino acids isolated from that cell. This isomer of 2-aminonorbornane-2-carboxylic acid inhibited at most only 75 to 80% of the uptake of either isoleucine or leucine, although the last two amino acids inhibited completely and homogeneously the uptake of the norbornyl amino acid. The nature of each of these inhibitory actions suggested that the synthetic amino acid can serve as a model substrate specific to a single route of entry serving for leucine and isoleucine, a conclusion supported by its failure to inhibit the component of uptake of leucine retained in the presence of isoleucine. Furthermore, the structural rigidity of the norbornyl amino acid permitted a partial description of a biochemical recognition site serving for transport into E. coli.