220 Essays in Biochemistry 



Arginine formation can be resolved into two enzymatically distinct 

 steps. The first of these, reaction 3, involves the condensation of citrul- 

 line with aspartic acid to form the relatively stable intermediate 



NH COOH 



II I 



C— OH + NH 2 CH + ATP -> 



I I 



NH CH 2 



+ ADP + H3PO4 (3) 



argininosuccinic acid. This is followed, as shown in reaction 4, by 

 a cleavage which liberates arginine by detaching fumaric acid. 



NH COOH NH COOH 



C NH CH 



NH CH 2 



C— NH, CH 



I + II 



NH CH 



(4) 



(CH 2 ) 3 

 NH 2 CHCOOH 



Argininosuccinic 



acid 



COOH 



(CH 2 ) 3 

 NH 2 CHCOOH 



Arginine 



COOH 



Fumaric 



acid 



The nitrogen atom acquired by citrulline can be donated only by 

 aspartic acid and not by NH 3 or glutamic acid, as the earlier experi- 

 ments with slices and homogenates appeared to indicate, nor by any 

 other amino acid. 



Argininosuccinic acid is a guanidine derivative, and the reaction by 

 which it is formed is depicted as a condensation between aspartic acid 

 and the tautomeric isourea form of citrulline, analogous to the chemi- 

 cal synthesis of guanidines from amines and S-methylisothiourea or 

 O-methylisourea. The structure of argininosuccinic acid has been sub- 



