Phagocytosis prompts a rapid respiratory burst with activation of the enzyme glucose-6-phosphate dehydrogenase: the hexose monophosphate shunt pathway. Subsequently, the enzyme NADPH oxidase, situated on the inside of the phagolysosome, reduces oxygen to the superoxide ion in tandem with reduction of NADPH. The superoxide ion is capable of killing by means of its reactivity. Alternatively, it is converted by the enzyme superoxide dimutase into toxic hydrogen peroxide. When present, the enzyme myeloperoxidase may further convert hydrogen peroxide to a halogen derivative e.g. HOCl when chloride ions are present. This is an extremely potent oxidant and antimicrobial.
Neutrophils and blood monocytes both contain and use the myeloperoxidase enzyme. Mature macrophages may be able to produce sufficiently toxic levels of radicals without needing the myeloperoxidase enzyme, which they do not possess.
There is a cytoplasmic system to neutralize any hydrogen peroxide which leaks from the phagolysosomes. The enzymes glucose-6-phosphate dehydrogenase, glutathione reductase and glutathione peroxidase detoxify to water.
Defects in each of the enzymes listed can have serious effects in terms of ability to defend against microbes; the most important are:
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