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

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.