178 Essays in Biochemistry 



nitrogen-sparing action by inhibiting step II of the urea cycle, one 

 may anticipate a decline in the specific rate of utilization of aspartic 

 acid in the synthesis of urea and no change, or possibly a rise, in the 

 concentration of hepatic ammonia. However, in view of the fact that 

 the specific rate of step II would also decline in the event of the slow- 

 ing of step I, only the anticipated effect on the ammonia concentra- 

 tion is of interpretive value in this case. 



In order to arrive at the correct interpretation we will consider the 

 kinetics of utilization of N 15 -ammonia in steps I and II of the urea 

 cycle. In the scheme shown, a is the amount of N 15 originally present 

 as N 15 H 3 ; Si is the fraction of N 15 H 3 which, per unit time, is used in 

 the synthesis of citrulline via step I; s 2 is the fraction of N 15 , appearing 

 in aspartic acid, which, per unit time, enters the urea cycle via step II; 

 s 3 is the fraction of N 15 H 3 which, per unit time, is transformed to 

 aspartic acid; and s 4 is the fraction of N 15 of aspartic acid which, per 

 unit time, is incorporated into body proteins. U\ and c/ 2 are the 

 amounts of N 15 which are ultimately utilized in steps I and II, re- 

 Step I Step II 



Ammonia > Aspartic acid > Proteins 



spectively. The assumed irreversibility of the utilization of ammonia 

 in the formation of aspartic acid is in conformity with the view, pre- 

 viously stated, that the reaction between ammonia and a-ketoglutaric 

 acid stongly favors the formation of glutamic acid, as well as with the 

 observation that aspartic-glutamic aminophorase of rat liver favors 

 the formation of aspartic acid in the ratio of 2 to l. 12 Theory shows 

 that when all of the administered N 15 is completely distributed between 

 urea and the body proteins (neglecting the relatively slow return of 

 isotope from labeled tissue proteins) : 



a (si + s 3 ) (s 2 + s 4 ) 



