Biological Science: Defective Synthesis of α and β Globin Chains in Lead Poisoning

Abstract

THE cells of many tissues, including bone, red cells, liver, brain and nerves, absorb lead¹ which accumulates chiefly on the mitochondrial membrane. Here it disturbs mitochondrial metabolism and produces the swelling and disruption revealed by electron microscopy². The most obvious metabolic defect is the inhibition of the synthesis of haem (and porphyrin). Lead inactivates at least three mitochondrial enzymes in the haem pathway (δ aminolaevulinic acid synthetase³, δ-aminolaevulinic dehydrase³, and haem synthetase⁴). This aspect of lead toxicity (reviewed in ref. 5) reduces haem production and leads to the accumulation and excessive excretion of several porphyrin intermediates. Lead seems to affect red cells chiefly by causing increased destruction and interfering with haemoglobin synthesis, as judged by the presence of ring sideroblasts in the bone marrow and hypochromia of the red cells. In normal red cell precursors the synthesis of haem and globin is finely balanced, but in diseases such as sideroblastic anaemia⁷ and iron deficiency anaemia (R. Barr, A. V. Hoffbrand and J. M. W., unpublished) a defect in haem synthesis leads to a disturbance of globin synthesis. A previous report indicated that globin synthesis was defective in lead poisoning⁸, but no reports have dealt with the synthesis and assembly of α and β chains, which we have now studied.