ENZYMATIC OXIDATION OF PHENOTHIAZINES BY LIPOXYGENASE H2O2 SYSTEM

Lipoxygenase (LOX) (EC 1.13.11.12) oxidized a wide range of phenothiaz ine (Pt) tranquillizers to their corresponding radical cations in the presence of H2O2 by means of an enzymatic chemical second-order mechan ism with substrate regeneration similar to that of horseradish peroxid ase. The optimum pH of LOX for this hydroperoxidase activity was in th e acid range (pH 3.0-4.0), as has been shown for other Pt oxidizing sy stems, such as peroxidase/H2O2 and haemoglobin. LOX showed Michaelis c onstants for Pt ranging from 1.4 to 8.5 mM and which, in some cases, e .g. trifluoperazine, displayed substrate inhibition. By contrast, it h ad a high affinity for H2O2 in the mu M to mM range. A new, previously undescribed plot, which relates the enzymatic affinity and the appare nt second-order decay of the cation radical, was developed to study th e influence of the 2- and 10-substituents in the Pt ring. The implicat ions of this new plot and the LOX-mediated Pt oxidation are also discu ssed.