Haemoglobin--a frustrated oxidase? Implications for red cell metabolism.
The haem proteins can be considered, in one aspect of their function, as machines for activating oxygen. In the case of oxygen-carriers such as haemoglobin, the globin has evolved so that its conformation limits access to the haem group, with resultant reversible release of oxygen. However, distortion of the globin may allow either the discharge of oxygen as the activated product superoxide or, more threateningly, allow direct function of the haemoglobin as an oxidative enzyme. Support for this is shown by the reaction with acetylphenylhydrazine where haemoglobin functions as both an oxidase and oxygenase. An implication of oxidase activity is the potential to initiate free radical formation particularly with unsaturated lipids. Observations of the acetylphenylhydrazine reaction emphasize the role of glutathione as a free radical scavenger.