The halide complexes of myeloperoxidase and the mechanism of the halogenation reactions.
The spectral changes caused by the addition of halides to myeloperoxidase (donor:hydrogen-peroxide oxidoreductase, EC 1.11.1.7) have been investigated and the dissociation constants of the enzyme-halide complexes have been determined. The pH dependence of the dissociation constants suggests that halide binding is associated with a protonation step in myeloperoxidase. Myeloperoxidase catalyzes the peroxidative chlorination and bromination of monochlorodimedone. It is shown that at low pH, chloride acts as a competitive inhibitor with respect to H2O2, whereas at higher pH, H2O2 inhibits the chlorination reaction. The dissociation constant (Kd) of the spectroscopically detectable complex and the Km for chloride are considerably smaller than the inhibition constant (Ki) for chloride. These halogenation reactions are strongly pH dependent, the logarithm of the Km for chloride varies linearly with pH. The position of the pH optimum of the chlorination and bromination reaction is a linear function of the logarithm of the [halide]/[H2O2] ratio. A mechanism of the chlorination and bromination reaction is suggested with substrate inhibition for both hydrogen peroxide and the halide.
D002384:Catalysis; D055598:Chemical Phenomena; D002621:Chemistry; D003512:Cyclohexanones / Q000378:metabolism; D006219:Halogens; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009195:Peroxidase / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D011485:Protein Binding
D003512:Cyclohexanones; D006219:Halogens; C006991:chlorodimedone; D010544:Peroxidases; D009195:Peroxidase