266 2. ANALOGS OF ENZYME EEACTION COMPONENTS 



ascites cells occurs by both diffusion and active transport (Jacquez, 1961). 

 Certain amino acids accelerate this at lower concentrations (1 mM) and 

 competitively inhibit at higher (5 mM), while other amino acids (such 

 as L-alanine, L-lysine, and L-arginine) only inhibit. Oxender and Christen- 

 sen (1963) thoroughly studied the effects of many amino acids on the up- 

 take of neutral amino acids by ascites cells and found they fall into two 

 overlapping clusters, the transport systems apparently not being very 

 specific. 



The penetration of amino acids into the brain is probably important 

 for the metabolism and function of that tissue, and there appear to be 

 several transport systems available. Tyrosine enters the brain readily in 

 vivo and a specific transport is probably involved, since L-tyrosine pene- 

 trates more rapidly than D-tyrosine and the entry is potently inhibited by 

 certain other amino acids, particularly L-tryptophan, L-leucine, L-valine, 

 /5-fluorophenylalanine, and L-histidine (Chirigos et al., 1960). In phenyl- 

 ketonuria the blood levels of phenylalanine are high due to the inability 

 of the tissues to metabolize it to tyrosine. It is possible that these high 

 concentrations can interfere with the entry of other amino acids into the 

 brain and partially account for the central nervous system disturbances. 

 The uptake of five amino acids by rat brain slices is indeed inhibited by 

 L-phenylalanine (see accompanying tabulation) and it was felt that such 



Amino acid (2 raM) % Decrease of concentration gradient 



L-Proline 9 



L-Histidine 42 



L-Arginine 46 



L-Ornithine 47 



L-Tvrosine 70 



could occur in vivo (Neame, 1961). The transport of L-histidine is inhib- 

 ited by neutral aliphatic amino acids and short-chain diamino acids to a 

 degree dependent on the length of the carbon chain (Neame, 1964). Inhi- 

 bition by the dicarboxylic amino acids is not dependent on the chain length. 

 In general, the L-isomers inhibit more potently than the D-isomers. It was 

 suggested that histidine is transported by a system which transports most 

 other amino acids, but with different affinities, since the inhibitions are all 

 competitive. The synthetic amino acid, 1-aminocyclopentanecarboxylate, 

 is not metabolized but is actively transported in brain slices and ascites 

 cells, and the system involved must be the same as for methionine since 

 it is affected similarly by the same competitive amino acids (Ahmed and 

 Scholefield, 1962). Such transported but nonmetabolized amino acids may 

 well be of use in studying transport inhibition, since effects can be clearly 



