6533b856fe1ef96bd12b1dae

RESEARCH PRODUCT

Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid.

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description

Hypochlorous acid (HOCl) is the most powerful oxidant produced by human neutrophils and contributes to the damage caused by these inflammatory cells. It is produced from H2O2 and chloride by the heme enzyme myeloperoxidase (MPO). Based on findings that betalains provide antioxidant and anti-inflammatory effects, we performed the present kinetic study on the interaction between the betalains, betanin and indicaxanthin, with the redox intermediates, compound I and compound II of MPO, and its major cytotoxic product HOCl. It is shown that both betalains are good peroxidase substrates for MPO and function as one-electron reductants of its redox intermediates, compound I and compound II. Compound I is reduced to compound II with a second-order rate constant of (1.5+/-0.1) x 10(6) M(-1) s(-1) (betanin) and (1.1+/-0.2) x 10(6) M(-1) s(-1) (indicaxanthin), respectively, at pH 7.0 and 25 degrees C. Formation of ferric (native) MPO from compound II occurs with a second-order rate constant of (1.1+/-0.1) x 10(5) M(-1) s(-1) (betanin) and (2.9+/-0.1) x 10(5) M(-1) s(-1) (indicaxanthin), respectively. In addition, both betalains can effectively scavenge hypochlorous acid with determined rates of (1.8+/-0.2) x 10(4) M(-1) s(-1) (betanin) and (7.7+/-0.1) x 10(4) M(-1) s(-1) (indicaxanthin) at pH 7.0 and 25 degrees C. At neutral pH and depending on their concentration, both betalains can exhibit a stimulating and inhibitory effect on the chlorination activity of MPO, whereas at pH 5.0 only inhibitory effects were observed even at micromolar concentrations. These findings are discussed with respect to our knowledge of the enzymatic mechanisms of MPO.