The Enzymatic Synthesis of Uroporphyrin Pre- 



cursors* 



LAWRENCE BOGORAD, Department of Botamj, University of Chicago, 



Chicago, Illinois 



The interesting observations reported by Dr. Smith at this meeting 

 reveal some important facts about final steps in the formation of 

 chlorophyll. The present report will deal with studies on some early 

 steps in the biosynthetic chain of chlorophyll and the other biologi- 

 cally important porphyrins, including porph\Tins which are the pros- 

 thetic groups of the cytochromes which have received so much atten- 

 tion at these sessions. 



Shemin and his co-workers (1,2) have contributed much to the 

 understanding of the roles of glycine and of Krebs cycle intermediates 

 in the synthesis of 5-aminole\'ulinic acid (DAL) (Fig. 1) and have 

 shown that this compound is utilized in the biosynthesis of proto- 

 porphyrin and heme. Workers in several laboratories (3-5) have 

 demonstrated, with enzymes prepared from various sources, the 

 in vitro condensation of two molecules of DAL to form one of the 

 monopyrrole porphobiHnogen (PBG) (Fig.l). This condensation 

 thus effectivelj^ remo\'es DAL from the general metabolic currency 

 of the cell and commits it to use in porphyrin biosynthesis, for it has 

 been sho^^^l that the enzymatic conversion of PBG into porphyrins, 

 including protoporphyrin IX, can be catalyzed by cell-free prepara- 

 tions of Chlorella (6), hemolyzed avian erythrocytes (7), or other 

 tissues. 



The present work has been concerned with the steps involved in 

 the condensation of four molecules of PBG to make the first cyclic 

 tetrapyrrole in the biosynthetic chain under consideration. 



The simplest tetrapyrrole which could be formed from four mole- 



* The work reported here was made possible by support from the National 

 Science Foundation (G-618) and the National Institutes of Health (A-lOlO). It 

 was also supported in part by the Wallace C. and Clara A. Abbott Memorial 

 Fund of the University of Chicago. Some aspects of the work were also supported 

 by the Arthur Weinreb Memorial Fund in Botany of the University of Chicago. 



475 



