THE CONTROL OF HAEMOGLOBIN SYNTHESIS

Abstract

Summary1. Haem and globin are synthesized separately by living cells before their conjugation to form haemoglobin.2. Protohaem is the form of haem utilized in the structure of haemoglobin, myo‐globin, erythrocruorin, catalases, some peroxidases and cytochromes of class B. All cells capable of aerobic respiration have the potential ability to synthesize haem.3. The main control mechanism in haem production is exercised by the enzyme ALA synthetase, and by cellular control over the level of activity of this enzyme.4. Haem probably affects the rate of globin synthesis but an effect of globin on haem synthesis is uncertain.5. Many organisms synthesize a variety of globins, some apparently exclusive to particular developmental stages. We suggest that the multiplicity of types of globin, whether changing during development, or present in balanced proportions in the adult, are not the result of evolutionary selection but of non‐adaptive changes in multiple copies of the primitive globin cistron.6. Ontogenic changes in the type of globin synthesized seem to be effected by differing mechanisms in different organisms. In some animals the changes seem to occur within one line of cells, whereas in others there is evidence for replacement of one cell population by another as in the switch from the embryonic to the adult or from tadpole to adult form of haemoglobin.7. Both transcriptional and post‐transcriptional control mechanisms are involved in globin synthesis, but the effects of the cell cycle and cell division on such regulation deserve intensive study in eukaryotic systems. We suggest that studies of globin synthesis provide evidence favouring some form of ‘linear reading’ of the genetic message.8. The hormones thyroxine and erythropoietin both affect haemoglobin synthesis in at least some organisms, and there are similarities in the pattern of action of the two hormones on erythropoietic tissues.9. All classes of RNA must affect globin synthesis and the isolation of globin mRNA has provided a particularly useful biochemical tool.10. Haemoglobin synthesis in artificial heterokaryons is of considerable interest but still poorly understood.11. The final assembly of tetrameric haemoglobin involves the conjugation of free haem with αβ globin dimers, the β globin chains apparently remain bound to ribo‐somes until they join with an α globin from the cellular pool of α globin. The mixed tetramer which is the most common form of haemoglobin possesses functional advantages over tetramers of only one globin type.