Pfizer Handbook of Microbial Metabolites 43S 



such as Rhodopseudomonas spheroides, the following se- 

 quence has been shown: 



— 4NH3 — 4H 



4 Porphobilinogen > Uroporphyrinogen > Uroporphyrin III 



— 2H 



— 4CO2 



— 4H 

 Coproporphyrinogen > Coproporphyrin III 



--4H — 2CO2 



— 4H 

 Protoporphyrinogen > Protoporphyrin IX 



The reduced precursors may be the biologically active 

 species, and the porphyrins by-products stabilized by oxi- 

 dation.'^ 



Higher animals (as well as microorganisms) are ca- 

 pable of porphyrin synthesis, and, in fact, the above work 

 with photosynthetic bacteria was based on earUer labeling 

 experiments in animals,^' and porphobilinogen was first 

 isolated from the urine of humans with acute porphyria." 



Widely occurring enzymes convert porphobilinogen to 

 uroporphyrins, but it is difficult to isolate and identify the 

 intermediates. Apparently they are quite transitory. 

 Some interesting speculations have been published con- 

 cerning their nature.'^' ^''' The Wittenberg hypothesis, 

 based on the known transformations of porphobilinogen 

 by chemicals and enzymes, the extensive labeling studies 

 that have been published, and on the construction of mod- 

 els, is outlined in the following series of equations : 



'•"'David Shemin and D. Rittenberg, J. Biol. Chem. 166 621, 627 

 (1946); Norman S. Radin, D. Rittenberg and David Shemin, ibid. 184 

 745 (1950); Jonathan Wittenberg and David Shemin, ibid. 185 103 

 (1950); David Shemin and Jonathan Wittenberg, ibid. 192 315 

 (1951); Helen M. Muir and A. Neuberger, Biochem. J. 47 97 (1950); 

 David Shemin^ Charlotte S. Russell and Tessa Abramsky, /. Biol. 

 Chem. 215 613 (1954); K. D. Gibson, W. G. Lauer and A. Neuberger, 

 Biochevi. J. 70 71 (1958); K. D. Gibson, A. Neuberger and J. J. Scott, 

 ibid. 61 618 (1955); J. E. Falk, E. I. B. Dresel, A. Benson and B. C. 

 Knight, ibid. 63 87 (1956); E. I. B. Dresel and J. E. Falk, ibid. 63 

 388 (1956). 



1" R. G. Westall, Nature 170 614 (1952); G. H. Cookson and C. Rim- 

 ington, Biochem. J. 57 476 (1954). 



'^ David Shemin, Harvey Lectures 50 258 (1956). 



16 Jonathan B. Wittenberg, Nature 184 876 (1959). 



