Concerted proton-electron transfer between ascorbic acid and cytochrome b561

Ascorbic acid is an essential reductant in biology but its reducing power is paradoxical. At physiological pH the predominant form of ascorbate (the monoanion) is a poor electron donor because it oxidizes to the energetically unfavorable neutral free radical. The ascorbate dianion forms the relatively stable semidehydroascorbate radical anion and is a powerful electron donor but its concentration at neutral pH is insufficient to produce the reaction rates observed. For example, ascorbate rapidly reduces cytochrome b561 from adrenal medullary chromaffin vesicles. This fast reaction rate may be rationalized by a mechanism involving concerted proton-electron transfer rather than electron transfer alone. This would permit reduction of the cytochrome by the abundant ascorbate monoanion but would circumvent formation of unfavorable intermediates. This may be a general mechanism of biological ascorbic acid utilization: enzymes using ascorbic acid may react with the ascorbate monoanion via concerted proton-electron transfer.