PORPHYRINS 



paradox that whereas only the a-carbon atom of glycine is 

 utilized for porphyrin synthesis, yet no "Ci" compound can act 

 as a substitute. The product of the decarboxylation would then 

 be 6-aminolevulinic acid. Condensation of 2 moles of the latter, 

 by a Knorr type of condensation (Figure 5), would readily give 

 rise to a pyrrole in which the a-carbon atom of glycine would be 

 distributed in the positions previously observed. To test this 

 hypothesis 5-aminolevulinic acid was synthesized in three in- 

 dependent ways (28,29). This was done to insure the cor- 

 rectness of the structure. The compound synthesized had the 

 correct analysis and took up 1 mole of periodate. From the 

 periodate reaction the expected products, formaldehyde and 

 succinic acid, were isolated in excellent yields. Prior to our 

 synthesis of 5-aminolevulinic acid, Wynn and Corwin (36) had 

 prepared this compound by another series of reactions. 



In the initial experiments, unlabeled 5-aminolevulinic acid 

 was added to duck red blood cell hemolyzates along with either 

 C^^-labeled glycine or C^^-labeled succinate. The radioactivities 

 of the hemin samples isolated in these experiments were com- 

 pared with those obtained from controls in which the unlabeled 

 5-aminolevulinic acid was omitted. The rationale for these dilu- 

 tion-type experiments is as follows : if 5-aminolevulinic acid is an 

 intermediate formed from the condensation of glycine and suc- 

 cinate, any labeled 5-aminolevulinic acid formed from these 

 labeled substrates will be diluted by the added unlabeled com- 

 pound, and consequently this should be reflected in the lowered 

 radioactivity of the hemin samples synthesized in the presence of 

 unlabeled 5-aminolevulinic acid. It can be seen from Table I 

 that the hemin samples made in the presence of unlabeled 5- 

 aminolevulinic acid contained less C^"* than those of the controls 

 made either from C^Mabeled glycine or succinate (28,29). 

 These results, which are in full agreement with the hypothesis, 

 can also be explained, however, by the possibility that 5-amino- 

 levulinic acid is acting not as a diluent but as an inhibitor of 

 heme synthesis. To rule out the latter possibility, the 5-amino- 

 levulinic acid added in Experiment 2 (Table I) was labeled with 



525 



