Antibody catalysis of the oxidation of water

Recently we reported that antibodies can generate hydrogen peroxide (H2O2) from singlet molecular oxygen (O-1(2)*), 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 mote equivalents of H2O2 from O-1(2)*, 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 O-1(2)* 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 immunoglobulins against O-1(2)* and raise the question of whether the need to detoxify O-1(2)* has played a decisive role in the evolution of the immunoglobulin fold.