Haemoglobin oxygenase

The catabolism of haemoglobin yields haem, which is subsequently converted to bilirubin in a two-step process that takes place in the hepatocyte. First, the microsomal enzyme haem oxygenase cleaves the porphyrin ring of haem, generating biliverdin in an energy-utilising reaction. Following this, biliverdin is converted to bilirubin by the cytosolic enzyme biliverdin reductase. As the liver is the active site for biosynthesis of porphyrin and haem, deficiencies in some enzymes of the porphyrin pathway may lead to insufficient haem production and an increase in porphyrin levels, which causes acute porphyria attacks. 

The oxidation of haem, a complex consisting of iron and protoporphyrin which is derived from haemoglobin, is effected by haem oxygenase to produce biliverdin IXa. This is converted to bilirubin IXa by biliverdin reductase. The reaction speed of this process is governed by the haem oxygenase. This enzyme complex contains the inducible cytochrome P 450, which accelerates bilirubin production when the haemoglobin level is elevated. A small proportion of bilirubin (20-30%) is produced from the degradation of other metalloporphyrins. (s. fig. 3.1)... 

Porphyrins represent the prosthetic groups of haemo-proteins (haemoglobin, myoglobin, cytochromes, oxygenases, catalases, peroxidases, etc.). The chemical parent compound of the porphyrins is the tetranuclear pyr-rolic dye, porphin. The capacity for haem synthesis is common to almost all cells, but is especially important... 

Surprising perhaps, carbon monoxide is produced in the body as a result of the normal breakdown of haemoglobin from red blood cells. The enzyme, haem oxygenase, converts the haem group into bilirubin and releases CO into solution. Current research has even suggested that trace amounts of CO may have a physiological role, possibly acting as a neuromodulator. 

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