ANIMAL METABOLISM 



353 



Arginase is present in the livers of those species which excrete urea as the 

 main end product of nitrogen metabolism, but is absent from others 

 such as birds, reptiles, and insects which excrete uric acid instead of urea. 

 Evidently there must be some way by which ammonia is incorporated 

 into arginine in the body, in preparation for urea formation. A possible 

 method, suggested in 1932 by Krcbs and Henseleit, is known as the 

 ornithine cycle: 



NH2 



+ NH3 



(58) 



NH2 



I 



C=NH 



I 

 NH 



I 



(CH2)3 



+ H20 



HCNH2 



COOH 

 L-Arginine 



Splitting of the arginine which was formed would then give the end 

 product, urea, plus another molecule of ornithine and start the cycle 

 over again. 



Most investigators still regard this scheme as essentially correct, 

 although later work has shown that aspartic and glutamic acids are also 

 involved in the process and also that an energy source (probably ATP) 

 is necessary to drive the reactions in the direction indicated. According 

 to Ratner and Pappas the conversion of citrulline to arginine (reaction 

 58) probably does not occur simply by addition of ammonia, as shown 

 in the above equation, but rather by interaction with aspartic acid: 



KH2 



1 

 C=0 



I 

 NH 



I 



(CHo)3 



HCNH2 



I 

 COOH 



L-CitruUine 



COOH 



H,N— CH 



+ 



CH, 



I 

 COOH 



L-Aspartic acid 



(An 



intermediate 



condensation 



product) 



NH2 



I 



C=NH COOH 



I I 



NH HOCH 



-I +1 



(CH2)3 CH2 



HCNH2 COOH 



COOH 



L-Arginine 



L-Malic acid 



This indicates that the nitrogen of certain amino acids may be converted 

 into urea in the body without ever having existed as free ammonia. 



Another modification of the Krebs-Henseleit cycle was proposed by 

 Cohen and Grisolia. They presented evidence that the carbon dioxide 



