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.