Antibody Catalysis of the Oxidation of Water

Abstract

Recently we reported that antibodies can generate hydrogen peroxide (H 2 O 2 ) from singlet molecular oxygen ( 1 O 2 *). We now show that this process is catalytic, and we identify the electron source for a quasi-unlimited generation of H 2 O 2 . Antibodies produce up to 500 mole equivalents of H 2 O 2 from 1 O 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 H 2 O as an electron source, facilitating its addition to 1 O 2 * to form H 2 O 3 as the first intermediate in a reaction cascade that eventually leads to H 2 O 2 . 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 1 O 2 * and raise the question of whether the need to detoxify 1 O 2 * has played a decisive role in the evolution of the immunoglobulin fold.