62 The Nature of Biological Diversity 



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have so far seen the light of clay. However, there are some interesting 

 possibilities from the viewpoint of evolution. 



The material used comprised a number of species of elasmobranchs 

 which, as is well known, are large-scale producers of urea, and the 

 primary problem is whether or not they make urea by the same route 

 as that followed in mammals and amphibians. It is now widely though 

 not quite universally believed that urea formation follows the path- 

 ways shown in Fig. 3. Carbon dioxide and ammonia in the presence of 

 ATP and acetylglutamate give rise in some way that is still very ob- 

 scure to carbamyl phosphate. Ornithine is transcarbamylated by 

 carbamyl phosphate to give citrulline, which reacts then with aspartate, 

 giving argininosuccinate. This last product is split into arginine and 



Mechanisms of ureogenesis 

 (as generally accepted) 



acetylglutamate 

 ( i ) COg + NH3 + ATP >- carbamyl phosphate 



(ii) Carbamyl phosphate + ornithine >- citrulline 



(Hi) Citrulline + aspartate >- argininosuccinate 



(iv) Argininosuccinate *• arginine + fumarate 



(v) Arginine >■ ornithine -I- urea 



FIG. 3. Mechanisms of ureogenesis (as generally accepted). 



fumarate and the arginine is hydrolyzed by arginase to give urea and 

 regenerate ornithine, which can then be used over again. Most of the 

 enzymes involved have been rather recently more or less purified 

 and studied in considerable detail (see Brown and Cohen, 1960, for 

 references ) . Their results were published a few years after our own 

 work in this field began. 



A number of interesting problems came to mind at the start of this 

 work. In the first place, while arginase is present in the livers of all 

 urea-producing animals, it is normally confined to the liver. In elasmo- 

 branchs, however, it is present in every organ in the body; it would 

 be interesting to know whether, in view of its very great osmotic 

 importance, urea might be made not only in the liver as is usually 

 the case but in other organs as well. The whole business presents 

 special problems because one is faced with the determination of small 

 amounts of urea synthesis in the presence of some 2 to 2.5 per cent of 



