Journal
SCIENCE
Volume 293, Issue 5536, Pages 1806-1811Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1062722
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- NCI NIH HHS [CA27489] Funding Source: Medline
- NICHD NIH HHS [HD 36385] Funding Source: Medline
- NIGMS NIH HHS [GM43858] Funding Source: Medline
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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.
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