The effect of electron flow through a complete circuit on transition state
acid dissociation constants is used to explain the remarkable catalysis obs
erved in a redox reaction, the formation of compound I from native peroxida
se. The explanation for the huge shift in the dissociation constant of a di
stal 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 tra
nsfer is occurring in the opposite direction. Electron flow occurs in one d
irection for attainment of the transition state and in the opposite directi
on for product formation.