C. RIMINGTON 



Although we have obviously much more to do before we can 

 visualize the mechanism of synthesis of these pigments and their 

 interrelation, one to another, the results of this initial experiment do 

 suggest certain conclusions, namely 



1 The system is a good one for the study envisaged ; the small 

 quantity of haem generally obtainable is the most adverse feature. 



2 The high relative abundance of N 15 in the bacterial protein is 

 surprising and would at first sight lead one to suspect a high 

 degree of randomization but as preliminary figures* indicate 

 that the glycine content of the bacterial growth is of the order 

 of 10 per cent, this need not be so. 



3 The figure for the intracellular haem in run 4 indicates that 

 glycine N is specifically utilized (in part at least) for the synthesis 

 of protohaem by this system, thereby confirming Shemin and 

 Rittenberg's findings for man, rat and duck bloods. 



4 The much lower relative abundance of N 15 in the coproporphyrin 

 appearing in the medium than in the intracellular haem argues 

 against any assumption that the former is derived from the latter 

 by further transformation. Rather does it indicate a separate 

 synthesis of coproporphyrin. 



5 Since the coproporphyrin figure is considerably lower even than 

 that of the total cell mass (in which glycine constitutes roughly 

 10 per cent) it is difficult to see how any specific utilization of 

 glycine N can have occurred in the synthesis of the coproporphyrin. 



We have succeeded also in isolating the uroporphyrin I produced 

 in these experiments and, although the quantities are very small, it 

 should be possible by dilution to get at least approximate figures for 

 their relative N 15 abundance. Such results promise to be of much 

 interest. Whilst exercising the greatest caution at this stage, I would 

 point out that to jump to the conclusion that the molecule of 

 coproporphyrin is synthesized from the same structural units as is 

 protoporphyrin may be an unwarrantable assumption. Shemin and 

 Rittenberg's work refers only to protoporphyrin and recent work has 

 even cast serious doubt upon the interconvertibility of the one pigment 

 to the other 15 . 



We are attacking this problem from several different angles and 

 hope eventually to lay bare the details of the steps by which these 

 various porphyrin pigments are synthesized in the living cell. One 

 can not doubt that light will then be thrown upon the pathological 

 disorders of metabolism such as congenital and acute porphyria. 



Received July 1948 



* Kindly supplied by Dr. C. E. Work using a chromatographic method. 



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