Catalase (CAT) and myeloperoxiase (MPO) are heme-containing enzymes that have attracted much attention in their role in the etiology of numerous respiratory disorders such as cystic fibrosis, bronchial asthma, and acute hypoxaemic respiratory failure. However, the interrelationship and competition between the two enzymes, free iron accumulation, and reduction levels in non-enzymatic antioxidants at sites of inflammation is still lacking. Myeloperoxidase catalyzes the generation of hypochlorous acid (HOCl) from hydrogen peroxide (H₂O₂) and chloride (Cl^-).  Self-generated HOCl has recently been proposed to autoinhibit MPO through a mechanism that involves MPO heme destruction. Here, we investigated the interplay of MPO, HOCl, and CAT during catalysis, and explored the crucial role of MPO inhibitors and HOCl scavengers in protecting the catalytic site of both enzymes against oxidative damage mediated by HOCl. We showed that CAT not only competes with MPO on H₂O₂ but also scavenges HOCl. The protective role provided by CAT versus the damaging effect provided by HOCl depends in part on the ratio between MPO/CAT, and the affinity of the enzymes towards H₂O₂ versus HOCl.   The severity of such damaging effects mainly depends on the ratio of HOCl to heme content of the enzymes.  Beside its effect in mediating protein modification and protein aggregation, HOCl oxidatively destroys the catalytic sites of the enzymes which contain the porphyrin ring and iron. Thus, modulation of MPO/CAT activities may be a fundamental feature of catalysis, and functions to down-regulate HOCl synthesis and prevent hemoprotein heme destruction.

Conference Title

SFRBM 2013 - 20th Annual Meeting of the Society for Free Radical Biology and Medicine, At San Antonio, TX, USA

Conference Country

United States of America

Conference Date

Nov. 20, 2013 - Nov. 25, 2013

Conference Sponsor

society For Free Radical Biology And Medicine(SFRBM)

Additional Info

Conference Website