Nitrogen Transfer in Biosynthetic Mechanisms 227 



The whole metabolic burden of maintaining a low concentration of 

 NH 3 within the body was thus assigned to the ornithine cycle. 



This view of amino acid breakdown goes back to the early work 

 of Neubauer, Dakin, and Knoop on the oxidative deamination of 

 amino acids and was strengthened by the observations that many 

 natural and unnatural amino acids can undergo oxidative deamination 

 in liver slices and, later, by the isolation of fiavoproteins that arc 

 capable of catalyzing the interaction with oxygen, as shown in re- 

 action 8. 



NH 2 O 



R— C— COOH + 2 + H 2 -> R— C— COOH + NH 3 + H 2 (8) 



I 

 H 



A second mechanism of deamination was later proposed by Braun- 

 stein, consisting of transamination coupled to the dehydrogenation of 

 glutamic acid (reactions 9 and 10). 



NH 2 



R— C— COOH + a-Ketoglutaric acid ^ 



I 

 H 



O 



R— C— COOH + Glutamic acid (9) 



Glutamic acid + DPN + H 2 ^± 



a-Ketoglutaric acid + NH 3 + DPNH + H+ (10) 



Since both of these reactions are reversible, they can be used in the 

 direction of reductive amination for the synthesis of amino acids. This 

 combination of reactions accounts, in a more satisfactory way than 

 has yet been possible, for the incorporation of N 15 -labeled amino acids 

 and NH 3 into other amino acids isolated from the proteins of intact 

 animals. We now realize that nitrogen metabolism involves as much 

 synthetic activity as catabolic breakdown. A process such as reductive 

 amination can also be concerned with the intracellular removal of NH 3 . 



NH 3 is an extremely toxic substance and cannot be tolerated by 

 many organisms above a very low blood concentration. Teleologically, 

 the conversion of NH 3 to urea has the appearance of a detoxication 

 mechanism and has been frequently interpreted as such. As pointed 

 out in preceding sections, the nitrogen atoms of a number of bodily 



