Peroxynitrite: biochemistry, pathophysiology and development of therapeutics

O2− may be neurotoxic by fueling formation of hydroxyl free radical or peroxynitrite.

“O 2 ⅐Ϫ may be neurotoxic by fueling the formation of highly pro-oxidant hydroxyl free radical or peroxynitrite (Halliwell, 2006;Szabo ´et al., 2007).”

Coactivation of NADPH oxidase and iNOS promotes a reaction between O2− and NO that gives rise to peroxynitrite.

“Coactivation of NADPH oxidase and iNOS promote a reaction between O 2 ⅐Ϫ and NO⅐, which gives rise to highly pro-oxidant peroxynitrite (ONOO Ϫ ) (Szabo ´et al., 2007).”

The fate of NO is dramatically changed in the presence of other free radicals such as superoxide.

“Biologically, this means that the fate of NO is dramatically changed in the presence of other free radicals such as superoxide (O2˙̄) (2, 20–22).”

The best studied reaction of NO with other free radicals is the very rapid reaction of NO with superoxide to form peroxynitrite.

“The best studied of these reactions is the very rapid reaction of NO with superoxide to form peroxynitrite (2, 21, 22, 24).”

Superoxide combines rapidly with nitric oxide at an approximately diffusion-limited rate (k=6.7×10^9 M^-1 S^-1) to form peroxynitrite.

“Superoxide is known to combine rapidly with nitric oxide (NO·) at an approximately diffusion-limited rate (k=6.7×109 M−1S−1) to form peroxynitrite”

In the injured or diseased gut, inflammation leads to increased production of reactive oxygen species such as superoxide, hydrogen peroxide and hydroxyl radicals and reactive nitrogen oxides such as peroxynitrite, dinitrogen trioxide and nitrogen dioxide.

“In the injured or diseased gut, inflammation leads to increased production of reactive oxygen species such as superoxide, hydrogen peroxide and hydroxyl radicals and reactive nitrogen oxides such as peroxynitrite, dinitrogen trioxide and nitrogen dioxide[320].”

The presence of free radicals such as superoxide changes the fate of NO: once reacted, it forms peroxynitrite and can no longer bind to ferrous heme.

“The presence of free radicals such as superoxide (O2.−) [82-85] changes the fate of NO: once reacted, it forms peroxynitrite [82, 84, 85] and can no longer bind to ferrous heme [86].”