64 NITROGEN METABOLISM 



possess a leucine-alanine transaminase [ic]. Transamination 

 can therefore be visualized as being of some significance in 

 amino-acid synthesis provided the organism can either syn- 

 thesize one or more amino-acids from ammonia by a direct 

 route (e.g. the glutamic acid dehydrogenase system or 

 aspartase), or obtain suitable amino group donor amino- 

 acids from the environment. 



Metabolite analogues and the elucidation of metabolic pathways 

 Many enzyme systems are inhibited in a competitive 

 manner by substances similar in chemical structure to their 

 normal substrates: such substances are known as metabo- 

 lite analogues and have been used, for example, to study 

 the synthesis of tryptophan by Salmonella typhosa [15]. 

 Although a reaction inhibited in this fashion may be essential 

 for grow^th, nevertheless, growth may be possible provided 

 the medium is fortified in some way, i.e. by the addition of 

 substances antagonizing the effects of the inhibitor. Ideally, 

 the substrates of the inhibited reaction act as competitive 

 antagonists, whereas the products act in a non-competitive 

 manner. The grow^th of freshly isolated strains of Salm. 

 typhosa is dependent on tryptophan or indole, but non- 

 exacting strains frequently arise. The inhibitory effects of 

 /?-indoleacrylic acid on the growth of a non-exacting strain 

 were completely overcome by the addition of tryptophan. 

 Indole accumulated in the media of non-exacting strains 

 growing in the presence of limited amounts of tryptophan 

 and sub-lethal amounts of indoleacrylic acid, and was pre- 

 sumed to be the substrate of the reaction blocked by the 

 inhibitor. Serine was a powerful antagonist and high con- 

 centrations of this amino-acid also decreased the accumula- 

 tion of indole. Fildes therefore concluded that tryptophan 

 was synthesized by the condensation of serine with indole 

 and that indoleacrylic acid inhibited this reaction. The work 

 of Snell and Schweigert had already indicated that an- 

 thranilic acid might be an intermediate in the synthesis of 

 tryptophan by Lb. casei and Lb. arabinosus, and it was later 

 found that irrespective of their tryptophan requirements, 

 strains of Salm. typhosa secreted anthranilic acid into the 



