Despite early knowledge of the requirement for metals in the reactions of ferrocytochrome c with oxygen, the relative effectiveness of metals and the factors that modulate effectiveness remain unknown. We have compared the catalytic power of five metals and report the effects of pH and ligand on their effectiveness as catalysts. Catalysis by metal ions was greatest at higher pH, where the rate of aerobic oxidation was lowest. Iron (Fe2+), copper (Cu2+), vanadium(V) (V(V)), manganese (Mn2+), and aluminum (Al3+) were tested in combination with EDTA, ADP, histidine, or desferrioxamine (Des) at pH 2.6, 3.2, and 4.0. At pH 2.6, only vanadium(V) increased the initial rate of the oxidation of ferrocytochrome c (by 6.2-fold). At pH 4.0, however, all the metals markedly stimulated the oxidation of cytochrome c. The order of effectiveness was V(V)∙Des >> Cu∙ADP2+ > Fe∙EDTA2+ > Mn∙Des2+ > Al∙EDTA3+ (where the stated ligand represents the most stimulating one for a given metal). At pH 3.2 the metal complexes had intermediate effects, with vanadium again being the most effective. The preeminence of vanadium among the metals is novel. Where the heme crevice is closed (pH 4), transition metal ions mediated almost all of the reduction of oxygen, while at the lowest pH (2.6) transition metal ions were largely unnecessary. Vanadium(V) was the most active of the metals at all values of pH and the only metal to accelerate the oxidation of ferrocytochrome c at pH 2.6. Understanding of the range of biological actions of vanadium will not be complete without a knowledge of its redox reactivity within the components of biological systems.Key words: aerobic oxidation, ferrocytochrome c, transition metals, ligands, vanadium, iron, manganese, copper, aluminium.
