BULLETIN OF THE NEW ENGLAND MEDICAL CENTER 



various types of tissue cells tend to concentrate amino acids to 

 a characteristic extent. By specific ninhydrin procedures, tissue 

 and plasma filtrates were analyzed for glutamine, for glycine, 

 and for the sum of other amino acids, which will be called the 

 "residual" amino acids. Upon the basis of chloride and water 

 analyses, we were able to calculate the concentration of each 

 of these three in the cell water, and the distribution ratio be- 

 tween the cellular and extracellular water. Glycine was a for- 

 tunate choice; for some reason the glycine of the plasma and 

 tissue of the guinea pig is extremely variable. But the varia- 

 tions in plasma, liver, and muscle occur together so that fairly 

 constant distribution ratios are maintained. The liver cell con- 

 centration tends to be thirty-three times, and the muscle cell 

 concentration, nine times, that of the extracellular fluid. The 

 residual amino acids tend to be fifteen times as concentrated in 

 the liver cells, five times as concentrated in the muscle cells. 

 Most of the amino acids fed to guinea pigs were metabolized 

 quickly and had small effects upon amino acid distribution. But 

 certain ones were disposed of much more slowly and produced 

 high plasma and tissue concentrations. L-proline, L-histidine, 

 L-methionine and most of the DL-amino acids examined are 

 included. The ability of the cells to concentrate glycine was 

 strikingly reduced when such amino acids were fed. The higher 

 the plasma concentration, the more severe the effect. Similarly, 

 high glycine concentrations interfered with the ability of the 

 tissue cells to concentrate nonglycine amino acids. 



Here, we believe, competitive inhibition is occurring among 

 the amino acids. Biologic antagonisms have been recognized 

 between metabolites and their foreign analogues, or even be- 

 tween two analogous compounds both of which are supposedly 

 foreign to the organism, but here is antagonism among a group 

 of essential metabolites. The observations indicate that the con- 

 centrating function does not operate independently for each 

 amino acid. A single mechanism could scarcely concentrate 

 every one of the many amino acids and yet maintain steady cell 

 concentration^ in the face of the variations of the amino acid 

 mixtures presented. 



Protein synthesis obviously requires the presence at some 

 limiting concentration of every amino acid, essential or non- 

 essential, that must go into the protein molecule. When a 

 strongly asymmetric accumulation of amino acids results from 

 feeding or injection, the ability of the cells to retain other 

 amino acids will be handicapped and inhibition of growth or 



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