Disturbances of Haemoglobin Synthesis in 

 Lead Poisoning 



A. VANNOTTI 



This paper presents evidence that in lead poisoning there is an 

 inhibition of haemoglobin synthesis because the iron is prevented 

 from entering the porphyrin ring. This inhibition is localized in 

 the bone marrow, and particularly in the cytoplasm of the erythro- 

 blast. On the other hand lead poisoning does not disturb the 

 synthesis of the haem of cytochrome C. This is evidence that the 

 mechanism and site of haem synthesis are different for haemoglobin 

 and for the cellular haems. Increase of protoporphyrin in the blood 

 results from an inhibition of haemoglobin synthesis, which may be 

 caused either by the toxic action of lead, or by toxi-infectious 

 disturbances of haemoglobin synthesis, or by iron-deficiency anaemia. 



Lead poisoning is characterized by the appearance of an anaemia 

 and by a notable increase of porphyrin in the blood and in the urine. 

 This anaemia is due not only to a decrease in the production of haemo- 

 globin, but also to the toxic action of lead on the formation of 

 erythrocytes, which thus exhibit notable morphological modifications 

 and undergo an increased haemolysis, especially at the beginning of 

 the poisoning. The increase of porphyrin production is especially 

 found in the bone marrow and in the blood in the form of proto- 

 porphyrin ; this increase leads to the elimination of a porphyrin III, 

 i.e. a porphyrin corresponding to that of haemoglobin 1 ' 2 . 



We studied the mechanism of the poisoning 3 and concluded that 

 the presence of protoporphyrin was due to an inhibition of haemo- 

 globin synthesis in the bone marrow. C. Rimington 4 also came to 

 the conclusion that lead inhibited the incorporation of iron into the 

 molecule of protoporphyrin during haemoglobin synthesis (see also 

 R. Kark and A. P. Meiklejohn 5 ). 



However, other hypotheses have been put forward to explain the 

 presence of porphyrin. Thus, J. Waldenstrom 6 and Bjorkman 

 thought that the appearance of this pigment was related to a dis- 

 turbance of the metabolism of cytochrome and other haem-containing 

 respiratory enzymes. Again, P. Martini 7 thought that the proto- 

 porphyrin was eliminated from the organism prematurely, before 

 being combined with iron to form haemoglobin. 



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