Biosynthesis of Porphyrins 67 



Dr. Shemin, has it been possible to demonstrate the tricarboxyhc 

 acid cycle in the avian erythrocyte? 



Shemin: The activities found in the porphyrin agree with the theo- 

 retical prediction that the citric acid cycle is functioning. Dische, 

 working with fowl erythrocytes, has informed me that the whole cycle 

 exists in the erythrocytes. 



Rittenberg: Since the more serious part of this discussion is ended, 

 may I raise an objection to the unanimity which exists between Dr. 

 Wood and Dr. Shemin on what the precursor is. In actuality, this is 

 not a scientific but a semantic problem. I would rather go back to the 

 first compound which really works, setting aside theoretical arguments. 

 For that reason, I think acetic is still the best one. 



Shemin: Purely as a matter of semantics, I still disagree; the four 

 carbon atom compound is the more immediate precursor. The acetic 

 acid was used in this study but the same results should be found with 

 other members of the citric acid cycle. 



Gurin: I should like to ask what has happened to the one carbon 

 precursors. There was a good deal of work going on with formate and 

 formaldehyde. What is the position with respect to that now? 



Shemin: The a-carbon of glycine and formate or formaldehyde are 

 equivalent for the 2 and 8 positions of the purines, and it has been 

 th ought by some that they are equivalent in other biological reactions. 

 But in the porphyrins, the a-carbon of glycine is utilized, but formalde- 

 hyde, formate, methyl amine, cyanide and COg are not. Lardy did find a 

 little activity in the porphyrins after formate, but he did not do any 

 degradation. In preliminary studies with i^C labelled methyl alcohol 

 in an experiment in which you can compare the purines and porphyrins, 

 yo u find that while the 2 and 8 positions of guanine have 30,000 counts, 

 the individual methene bridges of the porphyrin have about 100 counts, 

 which is really insignificant; there was more activity in the pyrrole ring 

 from the Ci compounds than there is in the methene bridge. Glycine 

 and the one carbon compounds are just not equivalent for the methene 

 bridge carbon atoms. 



Neuberger: In the rabbit we had exactly similar experience. We 

 tried a number of one-carbon intermediates, not as many as Dr. Shemin, 

 but got completely negative results. 



