How do enzymes work? Effect of electron circuits on transition state acid dissociation constants.

The effect of electron flow through a complete circuit on transition state acid dissociation constants is used to explain the remarkable catalysis observed in a redox reaction, the formation of compound I from native peroxidase. The explanation for the huge shift in the dissociation constant of a distal histidine residue, in going from the resting enzyme to the transition state, is a complete electron circuit through many amino acid residues and hydrogen bonds which prevents the development of localized charge. The key feature is electron flow through the circuit at the instant that proton transfer is occurring in the opposite direction. Electron flow occurs in one direction for attainment of the transition state and in the opposite direction for product formation.