Biological Assimilation and Dissimilation of Nitrogen 529 



It was formerly thought that most a-amino acids were formed from the 

 corresponding >a-keto acids, by way of reductive amination or transamination. 

 Nowadays it is known that in the process of primary biogenesis the amino 

 groups are frequently incorporated into the molecules at earher stages of the 

 synthesis, so that many amino acids are not being synthesized from their keto 

 analogues, but rather from other amino acids by way of remodeUing of, or 

 further additions to, their side chains. 



As shown in Fig. i, glutamic acid is transformed, with retention of its original 

 nitrogen, into proline, hydroxyprohne, ornithine and arginine, Aspartic acid is 

 converted to homoserine, methionine, threonine, glycine, and (in bacteria) to 

 diaminopimelic acid and lysine; from threonine, via intermediate keto acids, is 

 formed isoleucine. Serine and glycine are interconvertible and undergo trans- 

 formation into cysteine, tryptophan, kynurenine and alanine. Phenylalanine is 

 the precursor of tyrosine, dihydroxyphenylalanine and thyroxine, etc. 



In Fig. I are also shown the principal intermediates of carbohydrate meta- 

 bolism, giving rise to 'genetic sequences' of amino acids in the course of bio- 

 synthesis. 



The biosynthetic paths of the amino acids and their secondary metabolic 

 transformations include a variety of reactions effected by enzymes containing 

 pyridoxal phosphate as the prosthetic group [7, 8, 3]. Pyridoxal enzymes catalyse 

 decarboxylation and racemization of amino acids, the formation and removal of 

 amino groups by transamination, and many reactions of condensation, replace- 

 ment and cleavage by which the skeletons of amino acids are remodelled. In 

 Fig. I transformations involving the action of pyridoxal enzymes are denoted 

 by the symbol PP. 



According to the theory of Braunshtein & Shemyakin [9], the reactions cata- 

 lysed by pyridoxal enzymes are made possible by the peculiar chemical properties 

 of the Schiff bases, or azomethines, formed by the condensation of amino acids 

 with the CO-group of pyridoxal. Owing to the pronounced electrophilic pro- 

 perties of the substituents on the a-carbon atom of such azomethines (and of 

 the tautomeric azomethines formed by shift of the double bond) the electron 

 density of the a-carbon atom is greatly lowered. This results in polarization and 

 weakening (activation) of the bonds between the a-carbon atom and its substi- 

 tuents and, in the case of certain structural prerequisites (in suitably substituted 

 amino acids), also of bonds at the ß- and y-carbon atoms (Fig. 2). 



That is why azomethines of this kind can readily undergo reactions of cleavage 

 or substitution (condensation) involving rupture of the weakened bonds, as 

 indicated in Fig. 2. Generally spoken, the properties and transformations of 

 such azomethines are similar to those of the analogous keto acids, rather than 

 of the original amino acids. 



Several of these transformations can occur non-enzymically when amino acids 

 interact under relatively mild conditions with free pyridoxal, especially in the 

 presence of certain metals (e.g., Cu, Fe, Al, Ni). The discovery and detailed 

 investigation of these model reactions is due to Snell and his associates [10, 11]. 

 In 1954, they published a general theory of pyridoxal catalysis [11], the essential 

 features of which coincide with those of our theory (Braunshtein & Shemyakin, 



34 



