256 Essays in Biochemistry 



porphyrin of the III series it can be seen from Fig. 6 that it is neces- 

 sary to lose a 1 -carbon-atom compound since there are three amino- 

 methyl side chains, and only two are required to condense the two 

 dipyrroles to the porphyrin structure. If the mechanism similar to 

 that outlined in Fig. 6 is concerned with porphyrin synthesis, it would 

 appear that this 1-carbon-atom compound given off could well be 

 formaldehyde. Consistent with this idea is our finding 17 that on the 

 conversion of porphobilinogen to porphyrins either by heating under 

 acid conditions 22 or by enzymatic conversion in cell-free extracts 18 

 formaldehyde was indeed formed. This was established by heating or 

 incubating porphobilinogen, labeled with C 14 in the aminomethyl group, 

 and subsequently isolating radioactive formaldehyde as the dimedon 

 derivative. 



It would appear that, on conversion of porphobilinogen to porphyrins, 

 formaldehyde from the aminomethyl group is formed and that any 

 postulated mechanism should take this into consideration. It is dif- 

 ficult at present to establish the structure of the intermediate tetra- 

 pyrrole compounds which are formed prior to the formation of proto- 

 porphyrin. However, we would like to suggest that these intermediate 

 tetrapyrrole compounds may be the more highly reduced state, con- 

 taining methylene bridge carbon atoms rather than methene bridge 

 carbon atoms, and consequently uroporphyrin and coproporphyrin are 

 oxidized products of the intermediates. 



The biosynthetic pathway for porphyrin synthesis, given above, may, 

 from a more general viewpoint, be looked upon as merely one aspect 

 of glycine metabolism. The a-carbon atom of glycine besides being 

 utilized for porphyrin synthesis is also known to participate in the 

 synthesis of several other compounds: the ureido groups of purines, 

 the /3-carbon atom of serine, methyl groups, and for formic acid. It 

 would appear that these different compounds and porphyrins may be 

 related via a metabolic pathway of glycine. If indeed these mentioned 

 compounds and porphyrin synthesis are related through a series of 

 reactions occurring with glycine, then an intermediate utilized for 

 porphyrin synthesis may have the same metabolic pattern as is known 

 for glycine. If the succinate-glycine cycle proposed in Fig. 7 16 were 

 the pathway by which all the compounds are related, then specifically 

 the S-carbon atom of 8-aminolevulinic acid should have the same 

 metabolic spectrum as the a-carbon atom of glycine. In a study carried 

 out in ducks and rats it was found that the S-carbon atom of this 

 aminoketone is indeed utilized for the ureido groups of purines, for 

 the /?-carbon atom of serine, for the methyl group of methionine, and 



