248 UNITY AND DIVERSITY IN BIOCHEMISTRY 



In addition, the synthesis of isoleucine and valine is blocked by the 

 absence of a single transaminase. 



The sum total of facts indicates that a-ketoisovaleric acid yields leucine 

 by decarboxylation and condensation with a Cg fragment. 



For the case of isoleucine and valine, the mode of biosynthesis is indi- 

 cated in Fig. 68, 



(q) Biosynthesis of Amino Acids Derived from Benzene 

 {Tyrosine, Phenylalanine, Tryptophati) 



The existence of mutants of E. coli and Aerobacter aerogenes requiring 

 for their growth the three amino acids containing the benzene ring, has 

 greatly aided the elucidation of the biosynthesis of these compounds. These 

 mutants require not only a mixture of the three benzenoid amino acids, but 

 also for the most part they require ^-aminobenzoate, ^-hydroxybenzoate 

 or a sixth factor, still unidentified. A large number of observations have been 

 made on mutants requiring the benzenoid amino acids — determination of 

 the substances accumulating in each case, study of competition between 

 compounds, etc. Further, at the enzyme level, comparative studies have 

 been carried out on vegetable tissues and micro-organisms, which syn- 

 thesize the benzene ring and on animal tissues which do not. The cofactors 

 of each enzyme, etc., have also been studied. All these investigations lead to 

 the conclusion that the intermediates in the synthesis of the benzene ring 

 are 5-dehydroquinic acid, 5-dehydroshikimic acid and shikimic acid. What 

 is the precursor of 5-dehydroquinic acid? On this point, so far, the mutants 

 have told us nothing. But a certain amount of information has been pro- 

 vided by the use of isotopes and from enzyme studies. This work shows that 

 the transformation of glucose into the benzene ring of tyrosine or phenyla- 

 lanine does not operate through the Krebs cycle. With the aid of labelled 

 glucose, using a mutant accumulating shikimic acid, it has been possible 

 to show that the carboxyl of this acid is derived from C-3 and C-4 of 

 glucose, the C-1 from C-2 and C-5 of glucose and C-2 of shikimic acid 

 from C-1 and C-6 of glucose. Hence the C-1 — C-2 — carboxyl portion 

 of shikimic acid comes from a degradation product of glucose, the four 

 other carbon atoms being of a more complex origin. Sedoheptulose-1, 

 7-diphosphate is an excellent precursor of shikimic acid and there are good 

 reasons to favour the theory which puts sedoheptulose as an intermediate 

 in the synthesis of the benzenoid amino acids. 



The terminal stage of the synthesis has had some light cast upon it by 

 the results of enzyme studies. It has been shown that prephenic acid is an 

 intermediate in the path from phenylalanine to tyrosine. Moreover, 

 phenylpyruvic acid also lies along the pathway of phenylalanine 

 synthesis. 



