644 XIII. HEMOGLOBIN AND PORPHYRIN SYNTHESIS 



From the stoichiometry of the formation of coproporphyrin III it follows 

 that: 



D{1 - y) = 0(1 - w - z) 

 or: B{\ - x) {I - y) = Bx(l - w - z) 



^' - ^^ ^^ - y^ =l-w-z (2) 



X 



From equations 1 and 2 follows: 



2x-l 



w = — (3) 



X 



We can now give the ratio of coproporphyrin I to coproporphyrin III 

 (I/III) as a function of x and y: 



I/III = ?^ = ^^-^ (4) 



/''' BH -x){l- y) 2(1 -x){\- y) ^^^ 



substituting the value of w from equation 3. 



Now, X must be slightly greater than 0.5, since if a: = 0.5, w = 0, and no 

 coproporphyrin I will be formed. Since the daily excretion of bile pigment 

 is 300 mg., and that of coproporphyrin less than 300 ng., w must normally 

 be of the order of 0.001, and somewhat higher in pathologic conditions. 

 Values of x of the order of 0.5001 to 0.5005 are thus indicated. If we put 

 X = 0.5005, I/III becomes 1.0 with y = 0.999, but 0.17 ts;^ith y = 0.994. 



A slight decrease of hemoglobin formation, i.e., of the coordinated 

 reactions 4 and 5 of Figure 8, will thus have a large influence on the 

 ratio of the two coproporphyrins. Assuming x to remain constant 

 we shall expect to find the ratio I/III to be either unaltered or in- 

 creased by increased hemopoiesis, according to whether only the 

 primary synthesis of precursor B or also y and z are increased. This 

 indeed has been found by Dobriner and Watson. A derangement of 

 hemopoiesis on the other hand, with decrease of y and z, will lead to 

 a preponderance of coproporphyrin III. 



In lead poisoning the increased protoporphyrin content of the 

 corpuscles can be explained by inhibition of iron incorporation, but 

 the anemia is much larger than can be due to this. The whole 

 hemopoiesis must be decreased, i.e., the formation of B\ but it is 

 also probably deranged by decrease of the fractions y and z. The 

 theory requires in such a case a preponderance of coproporphyrin III, 

 which has been observed. The action of methyl chloride in causing a 

 porphyrinuria in which coproporphyrin III is excreted may be 

 understood as partly due to a similar derangement of hemopoiesis; 

 but here in addition the formation of formic acid may perhaps play 



