Kinetics and mechanisms of mammalian heme peroxidase reactions. (1st December 2005)

• Record Type: Journal Article
• Authors: Dunford, H. Brian
• Is Part Of: Progress in reaction kinetics and mechanism. Volume 30:Number 4(2005)
• Page Start: 245
• Page End: 265
• Publication Date: 2005-12-01
• Subjects: Chemical kinetics -- Periodicals; 541.39405
• DOI: 10.3184/007967405779134029
• Languages: English
• ISSNs: 1468-6783

Abstract

The kinetics and mechanism of action of the most intensively studied mammalian peroxidases, myeloperoxidase and prostaglandin H synthase are critically reviewed. Evidence against currently favored mechanisms is presented. It is shown that myeloperoxidase has a strong defence mechanism against free hypochlorous acid, commonly thought to be its principal product in its bactericidal activity. Rather, after its two-electron oxidation of chloride ion, myeloperoxidase rapidly converts it into an enzyme-bound chlorinating intermediate, most likely a chlorinated distal imidazole ring. This species chlorinates taurine which may either be a transfer agent of Cl+ to other species or may act directly in attack on invading microorganisms. The currently favored mechanism of action of prostaglandin H synthase-1 is a branching chain mechanism in which Compound I is converted into a species containing a tyrosyl radical on the opposite side of the enzyme. Once the tyrosyl radical is formed it converts arachidonic acid into a peroxide in a cyclooxygenase reaction, independent of the peroxidase activity. This mechanism cannot explain the enhancing effect of small free radical scavengers, nor the fact that peroxidase activity continues unabated while the cyclooxygenase reaction is proceeding, nor the 2:1 ratio of small free radical scavenger to arachidonic acid consumption. A tightly coupling of peroxidase and cycloxygenase reactions appears to be the steady state mechanism, and the branching chain mechanism, if it occurs, is confined to a burst transient state phase.