The Biosynthesis of Porphyrins 253 



groups of succinate since i Fig. 7) these carbon atoms arise from 

 succinate. 



It can be seen from Table 3 that the same C 14 -distribution pattern 

 was found in protoporphyrin synthesized from S-aminolevulinic acid- 

 5-C 14 as from glycine-2-C 14 ; 50% of the C 14 activity resides in the 

 pyrrole rings and 50% in the methene bridge carbon atoms (see 

 Fig. 3). 17 - 18 



Also it can be seen from Table 4 that the same (^-distribution 

 pattern was found in protoporphyrin synthesized from 8-aminolevulinic 



Table 4. Distribution of C" Activity in Protoporphyrin Synthesized 

 from 8-Aminolevulinic A.cid-1,4-C 14 and from Siiccinate-1,4-C 14 



Molar Activity (%) in Fragments 

 of Porphyrin Synthesized from 



acid-l,4-C 14 as from succinate-l,4-C 14 ; ten carbon atoms are equally 

 radioactive, 40% of the C 14 -activity resides in pyrrole rings A and B, 

 60% of the activity resides in pyrrole rings C and D, and the carboxyl 

 groups contain 20% of the C 14 activity (see Fig. 6). 19 



Thus all the carbon atoms of protoporphyrin are derived from 8- 

 aminolevulinic acid. The role of 8-aminolevulinic acid in porphyrin 

 synthesis was also actively pursued by Neuberger and Scott, 2 " and 

 just subsequent to our initial finding they published a confirmatory 

 paper; further confirmation was published by Dresel and Falk. 21 

 Furthermore, it may be well to point out that the theoretical formu- 

 lation of the structure of the precursor pyrrole 16 is the same structure 

 which was determined for porphobilinogen 22 by Cookson and Riming- 

 ton, 23 a compound excreted in the urine of patients with acute por- 

 phyria. These findings make a-amino-/?-ketoadiptic acid an obligatory 

 intermediate; we have found experimentally that this /3-keto is indeed 

 an intermediate. Injection of 8-aminolevulinic acid or the diethyl ester 

 of a-amino-/?-ketoadipic acid gives rise to the urinary excretion of 

 porphobilinogen. 24 



