ANALOG INHIBITION OF MEMBRANE TRANSPORT 



265 



system (see accompanying tabulation) (Hagihira et al., 1961). Arginine 

 and cystine interfere more with lysine transport than with glycine trans- 

 port, whereas methionine behaves in the reverse manner, and there is 



/-I J. A.- % Inhibition of transport of : 



, , ., . Concentration 



little or no interference between glycine and lysine. Proline, histidine, and 

 glycine are actively transported across the intestinal wall and methionine 

 at eqiiimolar concentration completely inhibits this (Wiseman, 1954). This 

 intestinal transport carrier is limited to monoamine-monocarboxylates and 

 they compete with each other. In addition to a common carrier, there may 

 be an additional carrier for glycine and proline (Newey and Smyth, 1964), 

 and it was pointed out that although each carrier system would conform 

 to Michaelis-Menten kinetics, the total transport with two or more carriers 

 involved would not necessarily. 



Intestinal transport systems may react with only the l- or the D-form 

 of an optically isomeric pair. D-Methionine is accumulated and transported 

 against a concentration gradient by the rat intestine and this is blocked 

 completely by equimolar concentrations of L-methionine ( Jervis and Smyth, 

 1960). Similarly, the transport of L-I^^^-monoiodotyrosine, which involves 

 active accumulation of the amino acid in the gut wall, is inhibited by 

 many L-amino acids (the most effective being L-tryptophan, L-methionine, 

 L-leucine, and L-isoleucine) but scarcely at all by any of the four D-amino 

 acids tested (Nathans et al., 1960). L-Tryptophan, for example, at 10 mM 

 reduces the tissue/medium ratio from 8.85 to 1.55 and the inhibition is 

 apparently competitive. 



The active cumulative uptake of amino acids by ascites carcinoma cells 

 comprises several transport systems, each with a specific range of substrates. 

 The uptake of glycine-1-C^* {K,,, = 6.4 mM) is most strongly inhibited by 

 1-aminocyclopentanecarboxylate {K, = 1.47 mM), and this is competitive, 

 while the uptake of DL-methionine-S^^ {K„, = 1.7 mM) is inhibited best 

 by allylglycine {K^ = 0.86 mM). Glycine transport is moderately inhib- 

 ited by aUylglycine and less readily by furylglycine and thienylglycine 

 (Scholefield, 1961). On the other hand, the uptake of DL-leucine-1-C^^ 

 is stimulated by most of these inhibitors. Transport of L-tryptophan in 



