Biosynthesis of Haem 



At this point chemical theorizing stopped. The first decisive 

 experimental evidence concerning the building stones of the porphyrin 

 ring came from D. Shemin and D. Rittenberg 7 who found that in 

 man, after a large quantity of N 15 labelled glycine had been taken, 

 the N 15 abundance in the haemin isolated from the blood was 

 sufficiently great to denote a specific utilization of glycine in the 

 synthesis. The same school found that deuterium of deuteroacetate 

 also appeared in the blood haemin, presumably in the side-chains. 

 More recently still 8 they have utilized the nucleated erythrocytes of 

 the duck's blood and shown that N 15 glycine is incorporated into 

 haemin in vitro. 



Referring to an observation of H. Fischer and E. Fink 9 on a 

 chemical reaction between formylacetone and glycine, Shemin and 

 Rittenberg 7 suggest that the pyrrole ring may arise in vivo from 

 condensation between glycine and a p-ketoaldehyde, as follows : 



R CHq H R CHq 



I ! ; I II 



C=c— {OH Hj— C— COOH C = C 



+ I > H— C H— C— COOH 



I ! 3 N 



H • 



Enol ofP-ketoaldehyde -f glycine * 



R CHq 



I I 



C C 



H— C C— COOH 



\ / 



N 



I 

 H 



The carbon atoms of the methane bridges in the porphyrin structure 

 would thus be derived from the carboxyl groups of the amino acid. 

 Recent experiments with C 14 labelled glycine have shown, however, 

 that the carboxyl carbon atoms do not appear in haemin 10 although 

 the methylene carbons do 11 and there has been a tendency to interpret 

 the earlier evidence as an indication that not glycine itself but some 

 simpler substance derived from it is the real building stone of the 

 pyrrole ring. 



I do not think this view is correct. The alternative would be, of 

 course, that at some stage in porphyrin formation the carboxyl groups 

 of the glycine molecules are eliminated and I find strong support for 



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