222 



Essays in Biochemistry- 



Removal of this tautomer by phosphorylation would tend to displace 

 an unfavorable equilibrium mixture of citrulline tautomers in the 

 direction favorable to condensation. The energy of the pyrophosphate 

 bond is perhaps utilized just to promote this tautomerization. 



Whether or not condensation can be further broken down to partial 

 steps, reaction 3 is at present the only one of the four reactions that 

 is not detectably reversible, although a number of procedures designed 

 to detect reversibility have been carried out. 20 



Nitrogen Transfer in the Ornithine Cycle 



A condensed representation of the ornithine cycle, as it appears at 

 present, is given in scheme 3. Compound X is replaced by carbamyl 

 phosphate for convenience. Mention has already been made of the 

 highly provisional status of phosphorylated citrulline. The individual 



o=c 





NH 2 



HoNC- 



± ~ph 

 -O— P(OH) 2 < > H.NCOOH <-» NH 3 + C0 2 



NH 2 



-> RNH 2 



±H 3 P0 4 



/ 

 -> 0=C 



\ 



NHj 



NH 



I 

 R 



NH H H NH "*" NH 



f I I S +~ph // 



H 2 NC < HOOC— C— N— C < HOC 



\ t I -H3PO4 \ 



NH 1 HOOC— CH NH f NH 



I HC— COOH I I HCNH 2 COOH | 



R II H R I R 



HC— COOH 



HC— COOH 



I 

 H 



Scheme 3 (RNH 2 = ornithine) 



steps include (1) the formation of carbamic acid, (2) the formation 

 of carbamyl phosphate, (3) the transfer of the carbamyl group to the 

 terminal nitrogen of ornithine to form citrulline, (4) the condensation 

 of citrulline with aspartic acid to form argininosuccinic acid, (5) the 

 removal of fumaric acid to form arginine, (6) the hydrolytic cleavage 

 of arginine to form urea and ornithine. It may be seen that each 

 transformation involves a different mechanism of C-N attachment or 

 cleavage. The incorporation of these steps into a cycle by the action 

 of arginase represents, in view of our present knowledge, a diversion 

 from their more general functions toward a special requirement devel- 

 oped by the mammalian liver in connection with nitrogen excretion. 



