DAVID SHEMIN 



clue in the elucidation of the mechanism of condensation of the 

 succinate and glycine. It has also been demonstrated that a 

 succinyl intermediate, arising from the tricarboxylic acid cycle, 

 is the source of the remaining twenty-six carbon atoms of pro- 

 toporphyrin (24,30). The relationship of the tricarboxylic acid 



•COOH 



I 



CHp 



CH2 



^OOH 



•booH 



I 



CHo 



I ^ 



CH2 



■>tGLYClNE 

 ► 



•COOH 

 I 



CHo 

 I 

 CH^-- 



•cOOH 

 I 



CHo 

 I 

 CHp 



— - COR 



CH2 COOH 



'N' 



I0*C00H 



7*C00H 9 CHo 



I I 



6 CH2 8CH2 



(» 



*^;^ 



COOH 



9CHo 



II 



6CH3 8CH 



^ 3" 



A 



2 



/ 



•HC 



K 



9 CHo 

 II 



6CH3 8CH 



4 3 



B 



5 , 2 



r 



v^ 



'o' 



=C 



H 



H ^ • 



CH +*6C02 



j^^^ FROM 



— /y^ ' 0^ POSITIONS 



7 AND 10 



''c" 



^RADIOACTIVE 

 CARBON ATOMS 



6CH:» 8CH2 8CH2 6CH3 



9CHp 9CHo 



I I 



lO^COOH •coo H 10 



Fig. 4. The position of succinate in protoporphyrin and the labeling pat- 

 tern obtained in protoporphyrin synthesized from succinate-l,4-C'*. 



cycle to porphyrin formation was formulated previously as 

 shown in Figure 3. This relationship was further documented 

 by studying the synthesis of protoporphyrin from a-ketogluta- 

 rate-S-C^^ o;-ketoglutarate-l,2-C^^ and citrate-l,5-C^^. In each 

 case the predicted carbon atoms of the porphyrin were labeled 

 from the G^^-labeled substrate (35). The experiments in these 

 studies were carried out by incubating either whole (25) or 



522 



