Nitric oxide is a physiological substrate for mammalian peroxidases.
We now show that NO serves as a substrate for multiple members of the mammalian peroxidase superfamily under physiological conditions. Myeloperoxidase (MPO), eosinophil peroxidase, and lactoperoxidase all catalytically consumed NO in the presence of the co-substrate hydrogen peroxide (H(2)O(2)). Near identical rates of NO consumption by the peroxidases were observed in the presence versus absence of plasma levels of Cl(-). Although rates of NO consumption in buffer were accelerated in the presence of a superoxide-generating system, subsequent addition of catalytic levels of a model peroxidase, MPO, to NO-containing solutions resulted in the rapid acceleration of NO consumption. The interaction between NO and compounds I and II of MPO were further investigated during steady-state catalysis by stopped-flow kinetics. NO dramatically influenced the build-up, duration, and decay of steady-state levels of compound II, the rate-limiting intermediate in the classic peroxidase cycle, in both the presence and absence of Cl(-). Collectively, these results suggest that peroxidases may function as a catalytic sink for NO at sites of inflammation, influencing its bioavailability. They also support the potential existence of a complex and interdependent relationship between NO levels and the modulation of steady-state catalysis by peroxidases in vivo.
Abu-Soud
H M
HM
Department of Cell Biology and Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. abusouh@ccf.org
Hazen
S L
SL
D000818:Animals; D002384:Catalysis; D006801:Humans; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D013379:Substrate Specificity; D013552:Swine
D009569:Nitric Oxide; D010544:Peroxidases