PORPHYRINS 



Thus all the carbon atoms of protoporphyrin are derived 

 from 5-aminolevulinic acid. The role of §-aminolevulinic acid 

 in porphyrin synthesis was also actively pursued by Neuberger 

 and Scott (17), and just subsequent to our initial finding they 

 published a confirmatory paper; further confirmation was 

 published by Dresel and Falk (6). Furthermore, it may be well 

 to point out that the theoretical formulation of the structure of 

 the precursor pyrrole (28) is the same structure which was 

 determined by Westall (32) and by Cookson and Rimington 

 (3) for porphobilinogen, a compound excreted in the urine of 

 patients with acute porphyria. The utilization of 6-amino- 

 levulinic acid for porphyrin formation adds to the certainty that 

 porphobilinogen (7) is an intermediate in porphyrin synthesis. 

 These findings make a;-amino-,8-ketoadipic acid an obligatory 

 intermediate, and we have found experimentally that this 

 jS-keto is indeed an intermediate. Injection of 6-aminolevulinic 

 acid or the diethyl ester of a:-amino-/3-ketoadipic acid gives rise 

 to the urinary excretion of porphobilinogen (31). 



The condensation of "active" succinate and glycine to 

 form 5-aminolevulinic acid subsequently, thus far appears to 

 require the partially intact structure of the red blood cell. It 

 has been found that whereas 5-aminolevulinic acid can be con- 

 verted to protoporphyrin in either an homogenized preparation 

 or a cell-free extract, the conversion of succinate and glycine to 

 porphyrin takes place only with intact cells or with those cells 

 which have been hemolyzed with water (23,29). Homogenized 

 preparations obtained in a blendor are no longer capable of 

 synthesizing protoporphyrin from succinate and glycine (Table 

 V). It would appear that on homogenization the functional 

 activity of only those enzymes of the system that are involved in 

 the condensation of succinate and glycine is lost. However, the 

 finding that 5-aminolevulinic acid can be converted to proto- 

 porphyrin in a cell-free extract opened up the possibility that 

 soluble enzymes, concerned with each of the steps in this con- 

 version, could be isolated. 



Indeed, it was subsequently and independently found in 



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