Proton-coupled electron transfer promotes the reduction of ferrylmyoglobin by uric acid under physiological conditions

Abstract

The hypervalent muscle pigment ferrylmyoglobin, MbFe(IV)O, is not reduced by urate monoanions at physiological conditions despite a strong driving force of around −30 kJ mol⁻¹ while for low pH, uric acid was found to reduce protonated ferrylmyoglobin, MbFe(IV)O,H⁺, efficiently in a bimolecular reaction with k₁ = 1.1 ± 0.1 × 10³ L mol⁻¹ s⁻¹, ΔH^‡ = 66.1 ± 0.1 kJ mol⁻¹ and ΔS^‡ = 35.2 ± 0.2 J mol⁻¹ K⁻¹. For intermediate pH, like for anaerobic muscles and for meat, proton-coupled electron transfer occurs in a transition state, {MbFe(IV)O⋯H⁺⋯urate}^‡, which is concluded to be formed from uric acid and MbFe(IV)O rather than from urate and MbFe(IV)O,H⁺ with k₃ = 9.7 ± 0.6 × 10² L mol⁻¹ s⁻¹, ΔH^‡ = 59.2 ± 0.1 kJ mol⁻¹ and ΔS^‡ = 11.5 ± 0.3 J mol⁻¹ K⁻¹. The activation parameters as calculated from the temperature dependence of the pH-reduction profile in aqueous 0.067 mol L⁻¹ NaCl (from 25 °C up to 40 °C), support a mechanism for reduction of hypervalent heme iron, where initial proton transfer to oxo-iron initiates the intermolecular electron transfer from urate to ferrylmyoglobin. The concentration of the powerful prooxidant ferrylmyoglobin increases strongly during digestion of red meat in the stomach. A concomitant increase in uric acid concentration may serve as an inherent protection against radical formation by ferrylmyoglobin.