Biological Assimilation and Dissimilation of Nitrogen 535 



Burris and others), studies on amino acid synthesis in 'wild' and mutant strains 

 of micro-organisms (Snell, Adelberg, Meister, Fincham, and others), and on the 

 effects of specific inhibition of single enzymes on the synthesis of amino acids 

 in animal tissues in vitro and in vivo (Braunshteïn and colleagues). 



The concordant resvilts of all these investigations have shown that glutamic 

 acid is the first organic product of nitrogen assimilation in most organisms. All 

 other amino acids are formed by transamination of various carbonyl compounds 

 (usually a-keto acids) directly with glutamate or with amino acids having formerly 

 obtained their amino groups from glutamic acid, and by secondary transforma- 

 tions of the structural skeletons of glutamate and of other primary amino acids. 



Glutamic acid is also an intermediate link in many important processes leading 

 to the dissimilation of amino acids or to their conversion into secondary nitro- 

 genous metabolites [3, 15; vide infra]. 



The fimdamental importance of indirect paths of assimilation and dissimila- 

 tion of nitrogen, based on linkage of transamination reactions with specific 

 enzymic transformations of the aminodicarboxyhc acids, was suggested in 1937- 

 39 in Braunshteïn's first communications on enzymic transamination [17]. This 

 concept has later been developed and supported by experimental evidence in a 

 series of papers from this laboratory [14, 15, 18, 19]. Attention was focussed, in 

 the first place, on the mechanisms of indirect reductive amination of a-keto acids, 

 or 'transreamination' (Braunshteïn), and of indirect oxidative deamination of 

 natural amino acids, or 'transdeamination', through the linked action of glutamic 

 dehydrogenase and aminopherases, according to scheme 3 (Fig. 3). 



With regard to the synthesis of amino acids, especially in plants, similar hypo- 

 theses have been proposed by Euler (1938) and Virtanen (1939). 



The idea of the general importance of such indirect transformations in nitro- 

 gen metabolism has for some time been viewed sceptically by many leading bio- 

 chemists. The main objections rested on the erroneous opinion (P. Cohen and 

 others) that only a few amino and keto acids could participate in transamination. 

 This argument has been invaHdated by the discovery, since 1950, of various 

 widespread aminopherases which catalyse transamination reactions involving 

 not only all natural a-amino acids, but also the transfer of ß-, y-, 8 and e-amino 

 groups [3, 7, 8, 13]. 



To-day it is almost generally accepted that a-oxoglutarate is usually the 

 practically unique substrate of direct reduction amination, whereas other 

 amino acids are the products of transreamination and(or) remodelling of carbon 

 skeletons. (In some bacterial species, e.g. in Bacillus subtilis, which possesses a 

 DPN-dependent, reversibly-acting L-alanine dehydrogenase [31], alanine rather 

 than glutamate is probably formed as the main primary product of reductive 

 amination, from which the other amino acids derive their NH2 groups.) 



In mammals the tissues are devoid of significant L-amino acid oxidase activity. 

 In these animals the dissimilation of natural amino acids also proceeds through 

 the intermediary formation of glutamic acid, by way of transdeamination and 

 of a second indirect path associated with urea formation (see p. 540). 



The above statements are supported by a considerable body of experimental 

 evidence, obtained by Braunshteïn and his coworkers and by many other inves- 



