628 XIII. HEMOGLOBIN AND PORPHYRIN SYNTHESIS 



oxidase, the lastmentioned enzyme being less decreased than the 

 others, and evidently synthesized preferentially. Iron deficiency has 

 also been found to decrease the formation of hydrogenase in Clos- 

 tridium welchii (2105), and that of catalase in yeast {3151). 



In addition to iron and the simple building stones required for the 

 synthesis of porphyrins {cf. Section 7.), copper is also required for 

 the synthesis of the cytochromes a and cytochrome oxidase in yeast, 

 liver, and bone marrow {4.59,676,2475,2477,3151). Since cytochromes 

 b and c are far less aflFected by the lack of copper (459), copper prob- 

 ably plays a role in the oxidation of the vinyl side chains of proto- 

 hematin. In addition, it appears to be required also for the synthesis 

 of catalase {2483) and of hemoglobin, unless cytochrome oxidase is 

 necessary for the synthesis of these hemoproteins and the inhibition 

 of their formation by copper deficiency is indirectly caused by a lack 

 of the oxidase {cf. Section 3.3.3.). 



7. SYNTHESIS OF PORPHYRINS BY THE LIVING CELL 



7.1. Porphyrins as Intermediates and By-Products 

 of Hemoglobin Synthesis 



In Chapter XII, Section 3.4. (particularly Section 3.4.6.) it has 

 been shown that there is little evidence suggesting a derivation of 

 porphyrins in the animal body from preformed hemoglobin, and that 

 their formation as intermediates or by-products of hemoglobin syn- 

 thesis is far more likely. The porphyrin which is excreted under 

 conditions in which hemopoiesis is increased is of type I. Rimington, 

 Dobriner, and Rhoads have developed the theory according to which 

 the synthesis of the porphyrins is never completely specific, and that 

 in addition to type III porphyrin, which is used for hemoglobin 

 synthesis, some type I porphyrin which does not combine with iron 

 is always produced and excreted. Hence every increase in hemo- 

 poiesis will be accompanied by a corresponding increase in excretion 

 of coproporphyrin I. The theory of porphyrin formation in the animal 

 body will be discussed in the next section. Here we add some further 

 evidence to that mentioned already in Chapter XII, Section 3.4. 



After phenylhydrazine administration the increase of porphyrin 

 excretion occurs not when the bile pigment formation is maximal, but 

 at a later stage when hemopoiesis and reticulocyte formation is 

 maximal (Dobriner and co-workers, 601,605). After hemorrhage, 

 coproporphyrin I excretion is increased and reaches its maxinmm 

 after about ten days, at the same time as the maximal reticulocyte 



