Metalloenzyme catalysis can require the coordinated action of multiple transition metal cofactors, each contributing a distinct chemical function: a cobalt-centered corrin (vitamin B12/cobalamin) cofactor undergoing cycles of oxidation-reduction and ligand (methyl) transfer, and a zinc(II) ion acting as a Lewis acid to lower the pKa of a bound substrate thiol, shifting its protonation equilibrium toward the reactive deprotonated form at physiological pH. This synthesizes principles from coordination chemistry (chelation and d-electron counts), electrochemistry (standard reduction potentials and coupled favorable/unfavorable half-reactions), and acid-base equilibrium (Henderson-Hasselbalch behavior and pKa perturbation by metal binding) within biochemistry/bioinorganic chemistry, illustrating how enzymes achieve catalysis through conformational dynamics and cofactor chemistry rather than through changes in reaction thermodynamics.
Metalloenzyme catalysis can require the coordinated action of multiple transition metal cofactors, each contributing a distinct chemical function: a cobalt-centered corrin (vitamin B12/cobalamin) cof…