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

Iyad Ali's picture
Research Title: 
Catalase Prevents Myeloperoxidase Heme Destruction and the Qeneration of free Iron mediated by Self-Qenerated Hypochlorous Acid
Authors: 
Iyad A Ali
Authors: 
Faten Shaeib
Authors: 
Ibrahim Abdulhamid
Authors: 
Ghassan M Saed
Authors: 
Subramaniam Pennathur
Authors: 
Husam M. Abu-Soud
Country: 
USA
Date: 
Sat, 2012-12-01
Research Abstract: 

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.