Phenylalanine and Tyrosine Synthesis 221 



of glucose or of a glucose derivative to form a six-membered 

 ring. In this event the benzene ring will become labelled in a 

 single position only. As mentioned earlier no decision can be 

 reached at present whether the benzene rings formed from 

 [1-^*C] glucose contain one or two labelled carbon atoms. We 

 favour the former possibility because metabolic reactions of 

 [1-i^C] glucose which would lead to labelling in meta positions 

 of the ring, and which do not involve acetyl units, are at 

 present difficult to visualize. The use of a more suitably 

 labelled precursor such as [6-^*C] glucose will be necessary 

 to ascertain whether a singly labelled ring structure is formed. 

 The experiments on amino-acid synthesis in yeast by 

 Baddiley, Ehrensvard et al. (1950) were similar in purpose to 

 ours. However, in their case yeast had been adapted to 

 grow on acetate as the sole carbon source. Under these 

 conditions all cell constituents, including phenylalanine and 

 tyrosine, are synthesized from acetate, and it becomes 

 difficult to distinguish metabolic pathways. The hypothesis 

 that benzene rings are formed by cyclization of glucose is in 

 complete accord with the distribution of acetate carbon found 

 in tyrosine by the Swedish workers, if it is assumed that under 

 their conditions acetate entered the citric acid cycle and was 

 transformed to glucose by reversal of the glycolytic path. In 

 spite of this agreement with an independent experimental 

 observation, the present evidence for the cyclization hypo- 

 thesis must be regarded as largely circumstantial. This 

 becomes particularly evident on consideration of the absolute 

 isotope concentrations in precursor and reaction product. 

 If the intact carbon chain of the glucose which was added to 

 the growth medium were converted to a six-membered ring, 

 the specific activity should be the same in the cyclization 

 product. Actually the benzene rings of phenylalanine and 

 tyrosine were found to contain only 50 and 62 per cent 

 respectively of this expected specific activity. Since the only 

 other major carbon source was acetate, which is not utilized 

 for the synthesis of the benzene rings under the conditions of 

 our experiment, this isotope deficit is difficult to explain. 



