Energy Sources for H^m Synthesis 89 



The action of lead might be either an inhibitory one upon 

 some essential enzymic system supplying either energy or a 

 building stone of the porphyrin ring, or alternatively lead ions 

 might be acting by blocking the incorporation of iron into 

 the ring system. There is some evidence from work on lead 

 poisoning to support this view, which I first put forward in 

 1936 (Rimington, 1936). The isotope technique may offer a 

 means of deciding between these alternative explanations of 

 the inhibitory action of lead and the problem is under further 

 active investigation. 



REFERENCES 



KiESE, M., and Schwartzkopf, W. (1937). Arch. exp. Path. Pharmak., 



204, 267. 

 Lemberg, R., and Legge, J. W. (1949). Hcematin Compounds and 



Bile Pigments. New York: Interscience. 

 Neuberger, a., Muir, H. M., and Gray, C. H. (1950). Nature, Lond.y 



165, 948. 

 Rimington, C. (1936). Onderstepoort J. vet. Sci., 7, 567. 

 Shemin, D. (1948). Cold Spr. Harb. Sym. quant. Biol., 13, 185. 

 Wittenberg, J., and Shemin, D. (1950). J. hiol. Chem., 185, 103. 



DISCUSSION 



Shemin: We did get marked inhibition with malonate and respiration 

 was inhibited about 70 per cent at a concentration as low as 10-^. All 

 the figures have not been published on it. Anaerobic conditions give 

 no synthesis. We haven't tried all the poisons, but most of them 

 inhibit the synthesis. 



Rimington: In view of w hat Dr. Shemin told us about the mechanism 

 of the synthesis, one would expect an inhibition by malonate. 



Wood: It seems to me that the extent of inhibition that one would 

 observe would depend to a great extent on the relative rate of synthesis 

 as compared to the rate of respiration. In other words, if the rate of 

 porphyrin synthesis were relatively slow as compared to the rate of 

 formation of C4 acids by respiration, then you would only see the effect 

 of malonate at the time when respiration was reduced to the point 

 where it became the rate limiting reaction. It is rather difficult in this 

 type of experiment to know whether you have reached that point or 

 whether you have not. 



Sloviter: I wonder if Professor Rimington has any notion why 

 haemolysis inhibits the haem synthesis. 



Rimington: I'm afraid I haven't. Of course, one could do many 

 things here, for example, add ATP, or inhibit ATPase and so on. I 

 wouldn't like to speculate any further on that point. 



