Antibody Catalysis of the Oxidation of Water

Abstract

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 immunoglobulins against 1O2* and raise the question of whether the need to detoxify 1O2* has played a decisive role in the evolution of the immunoglobulin fold.

Hydrogen peroxide production driven by UV-B in planktonic microorganisms: a photocatalytic factor in sea warming and ice melting in regions with ozone depletion?

“…WPO is a reaction of catalytic nature, whose initial rates decline due to reversible inhibition by its H 2 O 2 product (Wentworth et al 2001). Thus, in the presence of enough catalase activity, WPO proceeds at the maximal, initial rate.…”

“…Indeed, WPO-Cat activated by BA-UV-B plays a cyclic reaction that is by far the most exothermic in biology. Moreover, WPO-Cat using (Wentworth et al 2001), which is in the order of magnitude of that of solar origin that reaches the Earth's surface throughout the evolution. Even so, WPO has been thus far considered as a reaction with no apparent biological role, possibly because of its discovery in proteins that cannot be physiologically activated by solar UV-B.…”

“…1). The action spectrum of WPO extends from 270 to 320 nm (Wentworth et al 2001), a range including the spectrum of the biologically active UV-B (BA-UV-B) reaching the Earth's surface (Madronich and Flocke 1997). According to the photoequivalence law, one einstein of 300 nm-the typical wavelength of the BA-UV-B-yields 398.75 kJ per mol of H 2 O 2 produced and decomposed ( Fig.…”

“…The oxidation of water (H 2 O) by dioxygen (O 2 ) yielding hydrogen peroxide (H 2 O 2 ) in antibodies exposed to ultraviolet-B radiation (UV-B) (280-320 nm) is an amazing photocatalysis discovered a decade ago (Wentworth et al 2000(Wentworth et al , 2001. Of note, such a UV-B-driven process, hereafter referred to as water photooxidation (WPO), cannot take place in antibodies under natural conditions.…”

“…Of note, such a UV-B-driven process, hereafter referred to as water photooxidation (WPO), cannot take place in antibodies under natural conditions. However, preliminary studies showed that in the absence of UV-B, H 2 O 2 is also produced from H 2 O and singlet O 2 ( 1 O 2 *) (Wentworth et al 2000(Wentworth et al , 2001, which is an activated species produced in inflammatory processes. Due to the fact that H 2 O 2 is a potent microbicide, the latter H 2 O 2 production by 1 O 2 * in the absence of UV-B-the so-called antibody-catalyzed water oxidation pathway-was subsequently featured as a new chemical arm to immune defence (Nieva and Wentworth 2004), which, however, has been questioned by others (Parren et al 2003).…”