Orientation of oxygen in oxyhaemoproteins and its implications for haem catabolism

Abstract

Haem is degraded to bile pigments in the catabolism of haemoproteins in mammals and in the formation of photosynthetic pigments in algae. The first stage of this reaction involves oxygen attack at one of the four methene-bridge carbon atoms, which is ultimately eliminated as CO(ref. 1). The four bridges are not sterically equivalent (Fig. 1) and the bilirubin in mammalian bile and algal bile pigments consists almost exclusively of the alpha-isomers. Little is known about the structures of the ring-cleaving enzymes responsible, although microsomal haem oxygenase, which catalyses the breakdown of haem to biliverdin in mammals, has very similar spectroscopic properties to myoglobin. The degradation process has been simulated in vitro by a 'coupled oxidation' method in which the proportions of the four possible isomeric products depend on the nature of the globin moiety to which the haem is bound. We report here the use of an interactive computer display system to explore the relative accessibilities of the four methene bridges to a haem-bound oxygen molecule in myoglobin and in the alpha and beta chains of haemoglobin. Our calculated interaction energies agree well with the proportions of the four isomers that are observed experimentally.