IV 



COOH COCoA 



2 I "•" 2 I 



*CH2-NH2 (CH2)2 



Glycine | ~ 



COOH 



Succinyl 

 CoA 



PORPHYRIN SYNTHESIS 



COOH NH2 



89 



•CH — NH2 

 CO 



(CH2)2 



CO2. 



•CH2 

 CO" 



ch; 



/NH2 



•CH2 

 .^OC 

 CH2 



COOH CH2 CH2-COOH 



a-Amino-j3-Keto- | 



adipic COOH 



</"-Aminolevulinic 



Ac Prop Ac Prop 



CHj 

 I -^N" 



NH, H 



B 



^CH^ 

 I 



A 



Prop- 

 Ac - 



•CHj-NHj 

 Tripyrrole 



J 



NH 



, V , 2H 



-(3) M 



NH2 

 •CHj 

 C^ "CH 



II II 



c c 



CHg CH2 



COOH CH2 

 Porphobilinogen COOH 



r|JH2 

 'CH5- 



Ac Prop ^c Prop 



-CH,' 



i 



NH0-CH5 



-CH5 



-CH2-NH2 



@ ^"^ ^^°P (g) ^'"°P ^'^ 



Fig. 42. Proposed pathway of porphyrin synthesis. 



Twenty six carbon atoms are derived from acetate. The methyl group of acetate 

 is the precursor of carbons 3 to 6, and 8 and 9 of each of the pyrrole rings. The 

 two carboxyl groups are derived from the carboxyl group of acetate. Carbon 2 

 of the pyrrole rings and the methylene bridge carbons originate from the a- 

 carbon of glycine while the glycine amino group is the precursor of all of the 

 nitrogen of the molecule. The carboxyl group of glycine is not incorporated into 

 protoporphyrin. 



The distribution of radioactivity in the protoporphyrin molecule suggests that 

 all four pyrrole rings are derived from a common precursor pyrrole ; furthermore, 

 that carbon groupings g, 8, 3, and 6, 4, 5 probably come from the same compound 

 which contains a carboxyl group, from which carbon 10 is derived but which is 

 lost from all four carbon-6 atoms during the synthesis and from two of the carbon-g 

 atoms. A condensation between glycine and succinyl-CoA seemed involved 

 in the synthesis of the precursor pyrrole. Experiments with hemolyzed duck ery- 

 throcytes supported this hypothesis. It was shown that a-ketoglutarate-5-^'*C or 

 citrate- 1, 5-^'*C, was incorporated into carbon 10 of rings C and D, carbon atoms 

 previously shown to originate from acetate- i-^'*C. a-ketoglutarate- 1,2-^^*0 was 



Lileralure p. 124 



