PART II 



HEMOGLOBIN AND METABOLIC 

 DERIVATIVES 



THE BIOSYNTHETIC MECHANISM OF 

 PORPHYRIN FORMATION 



DAVID SHEMIN and JONATHAN WITTENBERG 



This discussion will deal with the origin of each of the carbon 

 atoms of protoporphyrin (the porphyrin moiety of haemo- 

 globin) and the conclusions, inferences and hypotheses we have 

 drawn from our data concerning the intermediary steps in 

 porphyrin formation. We will also attempt to demonstrate 

 that in the biological formation of the pyrrole unit two 

 relatively simple molecules are involved. 



The biological system used for most of the experiments in 

 this study was the nucleated red blood cells of the duck, which 

 can synthesize the porphyrin in vitro (Shemin, London and 

 Rittenberg, 1948, 1950). By merely incubating the blood 

 of a duck with an isotopically labelled precursor of the por- 

 phyrin, labelled hsem is formed. This limited system has 

 several obvious and distinct advantages over work with the 

 whole animal. Since many interconversions among the small 

 molecules do not take place in this in vitro system, the data 

 obtained are readily interpretable. 



Individual carbon atoms of the porphyrin molecule have 

 been isolated by suitable degradation procedures and the 

 following numbering system is used to designate any particular 

 carbon atom in the porphyrin without ambiguity (Fig. 1). 

 The pyrrole rings are designated A, B, C, D; the methene carbon 

 atoms of the bridges a, p, y, 8 and the ring carbon atoms are 



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