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 c atalytic, and we identify the electron source for a quasi-unlimited generat ion 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 th e electron source. On the basis of isotope incorporation experiments and ki netic data, we propose that antibodies use H2O as an electron source, facil itating 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 stu dies with xenon point to putative conserved oxygen binding sites within the antibody fold where this chemistry could be initiated. Our findings sugges t a protective function of immunoglobulins against O-1(2)* and raise the qu estion of whether the need to detoxify O-1(2)* has played a decisive role i n the evolution of the immunoglobulin fold.