The Biosynthesis of Haem 



C. RIMINGTON 



The problem of the chemical mechanism by which the haem 

 pigments, so important in the life of the cell, are synthesized 

 presents a challenge to the biochemist. Experience shows that the 

 organism can readily and rapidly synthesize the haem nucleus but 

 until recently nothing was known concerning the intermediate steps 

 involved ; even the intervention of protoporphyrin at the penultimate 

 stage is conjectural. 



In spite of the chemical possibility of different position isomers 

 of porphin derivatives, all natural ferriprotoporphyrins belong to 

 the isomeric series derivable from aetioporphyrin HI. Nevertheless, 

 series I porphyrins occur naturally in excreta and, in much larger 

 quantities, in certain pathological conditions having a genetical 

 basis. Numerous attempts have been made to represent the 

 biosynthesis of haems from simple pyrrole derivatives but each 

 encounters the difficulty of explaining the predominance of one 

 position isomer. To overcome this difficulty, Rimington postulated 

 an enzymic theory. 



The various suggested mechanisms of haem synthesis are briefly 

 reviewed and the modern evidence discussed which is based on 

 the use of iso topically labelled glycine and acetate. Both these 

 materials appear to be building stones for the porphyrin ring of 

 haem. Experiments by a group of workers, still in progress, on 

 pigment synthesis by C. diphtheriae are reported and whilst the 

 intracellular haems of this organism appear to be built up from 

 glycine {labelled N), the coproporphyrin III produced in the medium 

 would not appear to be derived from this precursor as the isotopic 

 N abundance is considerably lower even than that of the total cell 

 mass. It is emphasized that proto- and copro- porphyrins may 

 well derive from different synthetic processes as even the inter- 

 convertibility of these pigments is held in serious doubt. 



No greater challenge to the biochemist exists than the problem of the 

 biosynthesis of haemoglobin and of the haem systems of the cell. 

 The latter are of essential importance for the life of nearly every type 

 of cell while haemoglobin has been the subject of intense study and is 

 indispensable to the vertebrates. 



Until very recently all that could be said about the steps by which 

 haemoglobin was synthesized was that protoporphyrin was probably 



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