Effect of urate on the lactoperoxidase catalyzed oxidation of adrenaline

Abstract

Lactoperoxidase is an iron containing enzyme, which is an essential component of the defense system of mammalian secretary fluids. The enzyme readily oxidizes adrenaline and other catecholamines to coloured aminochrome products. A Km-value of 1.21 mM and a catalytic constant (k = Vmax/[Enz]) of 15.5 x 10(3) min(-1) characterized the reaction between lactoperoxidase and adrenaline at pH 7.4. Urate was found to activate the enzyme catalyzed oxidation of adrenaline in a competitive manner, the effect decreasing with increasing adrenaline concentration. Lactoperoxidase was able to catalyze the oxidation of urate. However, urate was a much poorer substrate than adrenaline, and it seems unlikely that urate activates by functioning as a free, redox cycling intermediate between enzyme and adrenaline. The activation mechanism probably involves an urate-lactoperoxidase complex.

Uric Acid and Thiocyanate as Competing Substrates of Lactoperoxidase

“…This reduction potential also makes urate a likely substrate for heme peroxidases. Indeed, it was shown early that mammalian peroxidases oxidize urate to allantoin (21,22). Recently, kinetic studies by us revealed urate to be a physiological substrate for the neutrophil enzyme myeloperoxidase (MPO) 3 (23).…”

“…High concentrations of LPO are present in human airway secretions, suggesting a function of LPO in the airway host defense against respiratory diseases (28). Apart from its main substrate thiocyanate, LPO oxidizes a variety of organic substrates, such as serotonin, tyrosine, tryptophan, melatonin, tryptamine and N-acetyltryptamine (29), thioanisole (30), the antibiotic benzylpenicillin (31), and adrenaline (22). Given the promiscuity of LPO, we considered that it may also readily oxidize urate.…”