228 Essays in Biochemistry- 



constituents are in part acquired from aspartic acid, including half of 

 the urea nitrogen, one of the pyrimidine nitrogens, and possibly the 

 6-NH 2 group of purines. Their origin in amino nitrogen actually 

 circumvents the formation of NH 3 . Aspartic acid nitrogen has to come, 

 ultimately, from the general pool of amino acids and can do so directly 

 by two successive transaminations involving glutamic acid, as shown 

 in reactions 11 and 12. 



Amino acids + a-Ketoglutaric acid ^ 



a-Keto acids + Glutamic acid (11) 



Glutamic acid + Oxalacetic acid ^ 



a-Ketoglutaric acid + Aspartic acid (12) 



None of these interconversions and transfers has the appearance of 

 a detoxication mechanism, nor are they primarily concerned with pro- 

 moting the excretion of nitrogen, yet they reduce the possibility of 

 undue NH 3 accumulation. Many metabolic processes, in effect, col- 

 laborate to this end. As aspartic acid assumes an increasing share 

 in the specific donation of nitrogen, the function of the highly active 

 glutamic-aspartic transamination becomes much easier to understand. 

 This transaminating pair appears as a link in the transfer of nitrogen 

 from amino acids to other nitrogenous constituents of the body through 

 aspartic acid. 



The formation of glutamine and asparagine, and their ability to 

 undergo transamination with other amino acids, 35 must also exert a 

 control on NH 3 levels. Unlike the amino acids from which they derive, 

 glutamine, and presumably asparagine, are freely permeable to the 

 liver cell, are present in high concentration in the blood, and undoubt- 

 edly play an important role in the transport of nitrogen to the liver. 30 



Energetics of NH 3 Formation and Nitrogen Transfer 



From an inspection of reactions 3 and 4, it may be seen that their 

 combined effect is to bring about detachment of nitrogen from aspartic 

 acid, incorporation of nitrogen in arginine, and liberation of fumaric 

 acid. In order to estimate the energy change that occurs when one 

 nitrogen atom is moved from the amino acid pool into urea, by way 

 of aspartic acid and citrulline, the shortest pathway is considered. 



Of the seven reactions covered in scheme 5, several involve little 

 change in free energy and can be neglected; they are the two trans- 

 aminations, the detachment of fumaric acid from argininosuccinic acid, 



