Antibody catalysis of the oxidation of water

Recently we reported that antibodies can generate hydrogen peroxide (H₂O₂) from singlet molecular oxygen (¹O₂*). We now show that this process is catalytic, and we identify the electron source for a quasi-unlimited generation of H₂O₂. Antibodies produce up to 500 mole equivalents of H₂O₂ from ¹O₂*, without a reduction in rate, and we have excluded metals Or Cl^- as the electron source. On the basis of isotope incorporation experiments and kinetic data, we propose that antibodies use H₂O as an electron source, facilitating its addition to ¹O₂* to form H₂O₃ as the first intermediate in a reaction cascade that eventually leads to H₂O₂. X-ray crystallographic studies with xenon point to putative conserved oxygen binding sites within the antibody fold where this chemistry could be initiated. Our findings suggest a protective function of immunogiobulins against ¹O₂* and raise the question of whether the need to detoxify ¹O₂* has played a decisive role in the evolution of the immunogiobulin fold.