The Biosynthesis of Porphyrins 



DAVID SIIEMIN 



There has been tremendous progress in the last 20 years in the eluci- 

 dation of the biochemical reactions and transformations which occur 

 in living organisms. Some of the general concepts which have emerged, 

 summarized very briefly, are that the basic reactions in the cells are 

 surprisingly simple, that the cell synthesizes its complex molecules from 

 relatively simple and available substances, and that there is a bio- 

 chemical unity in living matter. 



Although these concepts were perhaps not fully appreciated when 

 a study of the biosynthesis of porphyrins was begun 10 years ago, the 

 picture which has emerged is rather a good illustration of these basic 

 concepts. The studies have revealed that the complicated looking 

 molecule protoporphyrin is synthesized from two simple and avail- 

 able compounds, glycine and succinate, by relatively simple reactions. 

 Furthermore it has been established that the synthesis of this esoteric- 

 looking molecule is intimately related to the citric acid cycle, since the 

 "active" succinate utilized in porphyrin synthesis is produced in these 

 cyclic reactions. Although most of the investigations have been con- 

 cerned with the biosynthesis of protoporphyrin, it appears that all the 

 porphyrins in nature, including chlorophyll, in all different types of 

 cells are synthesized by the same basic pathway. The different por- 

 phyrins merely arise by modifications occurring in the side chains in 

 the (3 positions of the pyrrole units. 



In 1945 it was found that the nitrogen atom of glycine is the nitrog- 

 enous precursor of protoporphyrin in both man and rat. 1-3 Although 

 protoporphyrin (Fig. 1) consists of two types of pyrrole units, methyl- 

 and vinyl-bearing pyrroles, and methyl- and propionic acid-bearing 

 pyrroles, the finding that N 15 -labeled glycine was equally utilized for 

 these different pyrrole units 4,5 demonstrated that glycine was the 

 nitrogenous precursor of all four pyrrole units and suggested that a 

 common precursor pyrrole, the source of all four pyrrole rings of the 



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