It is generally accepted that the physiological function of myeloperoxidase is to produce hypochlorous acid. However, this green heme protein does not fit the classical definition of an enzyme. Usually an enzyme is specific in the reaction it catalyzes and in its choice of substrates. In contrast, myeloperoxidase has many and varied substrates, and catalyzes at least three different reactions. This indiscriminate catalytic power argues against a singular role for myeloperoxidase. Rather, it suggests that its function will be modulated by the local milieu. Therefore, we need to fully appreciate the complexity of its reaction mechanisms to understand how it acts within neutro-phil phagosomes during microbial killing and how it contributes to inflammation. In addition to hydrogen peroxide and chloride, potential physiological substrates for myeloperoxidase include superoxide, thiocyanate, tyrosine, tryptophan, urate, nitric oxide, and nitrite, and there are bound to be others. Their reactions also need to be considered when assessing the function of myeloperoxidase. In this chapter we outline the redox transformations that myeloperoxidase undergoes during turnover, and give examples of how the various alternative substrates influence its activity. We also take a kinetic modelling approach to predict how myeloperoxidase functions in the neutrophil phagosome and test what parameters are critical for efficient production of hypochlorous acid.
