632 XIII. HEMOGLOBIN AND PORPHYRIN SYNTHESIS 



7.3.2. Porphyrin Synthesis in Yeast. The study of the por- 

 phyrin synthesis in yeast was commenced by Fischer and co-workers 

 (811-813,830,875,876). Other fungi, such as Aspergillus oryzae, also 

 synthesize porphyrin. No preformed porphyrin, hematin, or pyrrole 

 compound is required in the medium (83^), which contained ammonia 

 or urea, glucose, and salts. A correlation between rate of fermentation 

 and porphyrin synthesis has been found by Fischer and Fink, and 

 Carrie and Mallinckrodt-Haupt (4-07; but cf. 1516). The porphyrin 

 formation is not due to an iron deficiency, since iron even increased 

 porphyrin formation, while hematin did not do so. Copper, lead, 

 arsenic, and vanadium were also found to cause an acceleration of 

 porphyrin synthesis. Under normal conditions the porphyrin is 

 coproporphyrin I and, hence, cannot be derived from the cell hematin 

 or cytochrome c (cf. 707,708,83^,1516). Mayer (1890) found that 

 porphyrin synthesis proceeds in the press juice of yeast, and con- 

 cluded from the observed inhibition by cyanide that the process is 

 enzymic. Sulfonal increases porphyrin formation by yeast (Thomas, 

 2799). 



More recently the process has been studied by Rimington {2269) 

 and by Kench and Wilkinson {1516). Rimington found that yeast 

 soon loses its ability to synthesize porphyrins. Press juices obtained 

 after incubation with toluene at 48°C. formed some porph\rin and, 

 by the addition of boiled extract of active yeast, the yield could be 

 increased sevenfold. Kench and Wilkinson {1516) found that more 

 porphyrin was formed when the autolysis of yeast at 19-22°C. pro- 

 ceeded in the presence of an ammonium salt. When glucose or other 

 carbohydrate was added, the porphyrin formation remained high. In 

 the presence of sugar, coproporphyrin I was formed, while starved 

 autolyzing yeast yielded predominantly coproporphyrin III. Sodium 

 fluoride or toluene inhibited the synthesis. From these results it can 

 be concluded that the synthesis of porphyrins is intimately linked up 

 with carbohydrate metabolism. 



8. SYNTHESIS OF THE PORPHYRIN NUCLEUS 



8.1. Previous Theories 



No convincing theory of the way in which the porphyrin nucleus 

 is synthesized in the animal or yeast cell has yet been devised. A 

 number of earlier suggestions are no more than speculations, not 

 supported by evidence. Tryptophane has often been assumed to be 



