]->. RITTENBF.RG AND D. SHEMIN 



(31). After the feeding of labeled amino acids, N^^ can be found in 

 the a-amino group of leucine, which suggests that a-ketoisovaleric 

 acid can be aminated. No N^^, however, is found in lysine, indicating 

 either that a-keto-e-aminohexanoic acid is not formed, or that it could 

 not be aminated if formed. In general, it is not possible by the use 

 of isotopic nitrogen to determine whether the carbon skeleton is essen- 

 tial. In certain special cases, such as that of histidine, it becomes 

 feasible. When the amino acid is isolated from rat tissues after the 

 administration of other labeled amino acids, it is found that all the 

 N^* is present in the a-amino group (34), none being found in the 

 imidazole ring. This, taken in conjunction with the nutritional re- 

 placeability of /-histidine by ^-histidine and by imidazole lactic acid 

 (9,10), forms direct evidence that the organism cannot synthesize the 

 histidine skeleton. It has been claimed that histidine is not essential 

 in man (30); by the feeding of a labeled amino acid to a human it 

 should be possible to settle this and other such problems. 



A detailed study of the N^^ concentrations in the four nitrogen 

 atoms of arginine isolated from the tissue of rats which have received 

 glycine labeled with N'^ indicates that the a-amino group is not sub- 

 jected to the reversible deamination-reamination reaction. On deg- 

 radation of the arginine, it is found that the nitrogen atoms of the 

 a- and 5-carbon atoms contain the same N^^ concentration (37). The 

 nitrogen on the 5-carbon atom of arginine cannot be involved in a 

 reversible deamination-reamination reaction since it is blocked by the 

 amidine group. Were the a-amino group subject to reversible de- 

 amination-reamination, the likelihood of its isotope concentration being 

 the same as that of the nitrogen on the 5-carbon atom would be small. 

 The mechanism for the formation of arginine does not seem to involve 

 the amination or transamination of the corresponding keto acid. The 

 introduction ol equal concentrations of N^^ in the a- and 5-nitrogen 

 atoms of arginine is l^rought abovu through a cyclic process involving 

 the formation of ornithine from proline (37). Only in the cases of glu- 

 tamic acid (7,8,13), aspartic acid (7,8), and alanine (7,8), are the 

 mechanisms for their formation from keto acids known with certainty. 

 It is known, of course, that the keto acids of some essential amino acids 

 may substitute for the amino acid in growth experiments; but the 

 mechanism of the amination is unknown. Therefore, other mecha- 

 nisms may exist for the formation of amino acids, such as conversion of 



274 



