Some Aspects of Nitrogen Transfer 

 in Biosynthetic Mechanisms 



SAHAH RATHER 



The origin of urinaiy urea has been one of the oldest concerns of 

 biochemistry as well as a major problem of nitrogen metabolism. The 

 attention it has received stems from the biochemist's great interest in 

 mammalian, and particularly human, physiology and pathology. Dur- 

 ing the last few decades, the novel concepts of Krebs were responsible 

 for bringing the whole problem much closer to solution. By visualizing 

 the formation of urea as a cyclic phenomenon, carried out through the 

 agency of intermediates acting as nitrogen carriers, he opened the 

 experimental approach to urea formation as a process of cellular me- 

 tabolism. 



In the past few years our detailed understanding of the reactions 

 which comprise the ornithine cycle of Krebs, along with general ad- 

 vances in our knowledge of intermediary metabolism, have caused our 

 attention to turn from the significance of these reactions in the forma- 

 tion of urea to their significance in the formation of arginine. The 

 individual reactions which lead to the formation of citrulline and 

 arginine now hold considerable interest. It is growing more evident 

 that these reactions are engaged in synthetic activities far beyond their 

 connection with the formation of two amino acids. A broader meta- 

 bolic network can be seen in which urea production assumes a place 

 as but one aspect of arginine metabolism. Urea is formed by a cir- 

 cuitous pathway, and it is only through the action of arginase that two 

 nitrogens can be conveniently removed as urea if such a pathway is 

 to be followed. The entire synthetic course, up to the arginase step, 

 is of general use metabolically. From this point of view, it becomes 

 economical for the living organism to employ elaborate mechanisms 

 for the formation of urea when they serve more than one function. 



Scheme 1 represents our present concepts of the various ramifications 

 of arginine metabolism with the original participants of the ornithine 



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