PMID- 9741578
OWN - NLM
STAT- MEDLINE
DCOM- 19981124
LR  - 20220330
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 25
IP  - 4-5
DP  - 1998 Sep
TI  - Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite, and 
      carbon dioxide.
PG  - 392-403
AB  - The roles of superoxide (O2.-), peroxynitrite, and carbon dioxide in the 
      oxidative chemistry of nitric oxide (.NO) are reviewed. The formation of 
      peroxynitrite from .NO and O2.- is controlled by superoxide dismutase (SOD), 
      which can lower the concentration of superoxide ions. The concentration of CO2 in 
      vivo is high (ca. 1 mM), and the rate constant for reaction of CO2 with -OONO is 
      large (pH-independent k = 5.8 x 10(4) M(-l)s(-1)). Consequently, the rate of 
      reaction of peroxynitrite with CO2 is so fast that most commonly used scavengers 
      would need to be present at very high, near toxic levels in order to compete with 
      peroxynitrite for CO2. Therefore, in the presence of physiological levels of 
      bicarbonate, only a limited number of biotargets react directly with 
      peroxynitrite. These include heme-containing proteins such as hemoglobin, 
      peroxidases such as myeloperoxidase, seleno-proteins such as glutathione 
      peroxidase, proteins containing zinc-thiolate centers such as the DNA-binding 
      transcription factors, and the synthetic antioxidant ebselen. The mechanism of 
      the reaction of CO2 with OONO produces metastable nitrating, nitrosating, and 
      oxidizing species as intermediates. An analysis of the lifetimes of the possible 
      intermediates and of the catalysis of peroxynitrite decompositions suggests that 
      the reactive intermediates responsible for reactions with a variety of substrates 
      may be the free radicals .NO2 and CO3.-. Biologically important reactions of 
      these free radicals are, for example, the nitration of tyrosine residues. These 
      nitrations can be pathological, but they also may play a signal transduction 
      role, because nitration of tyrosine can modulate phosphorylation and thus control 
      enzymatic activity. In principle, it might be possible to block the biological 
      effects of peroxynitrite by scavenging the free radicals .NO2 and CO3.-. Because 
      it is difficult to directly scavenge peroxynitrite because of its fast reaction 
      with CO2, scavenging of intermediates from the peroxynitrite/CO2 reaction would 
      provide an additional way of preventing peroxynitrite-mediated cellular effects. 
      The biological effects of peroxynitrite also can be prevented by limiting the 
      formation of peroxynitrite from .NO by lowering the concentration of O2.- using 
      SOD or SOD mimics. Increased formation of peroxynitrite has been linked to 
      Alzheimer's disease, rheumatoid arthritis, atherosclerosis, lung injury, 
      amyotrophic lateral sclerosis, and other diseases.
FAU - Squadrito, G L
AU  - Squadrito GL
AD  - Biodynamics Institute, Louisiana State University, Baton Rouge 70803-1800, USA.
FAU - Pryor, W A
AU  - Pryor WA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Free Radicals)
RN  - 0 (Nitrates)
RN  - 11062-77-4 (Superoxides)
RN  - 142M471B3J (Carbon Dioxide)
RN  - 26404-66-0 (peroxynitric acid)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Carbon Dioxide/*chemistry
MH  - Free Radical Scavengers
MH  - Free Radicals
MH  - Nitrates/*chemistry
MH  - Nitric Oxide/*chemistry
MH  - Oxidation-Reduction
MH  - Superoxides/*chemistry
RF  - 102
EDAT- 1998/09/19 00:00
MHDA- 1998/09/19 00:01
CRDT- 1998/09/19 00:00
PHST- 1998/09/19 00:00 [pubmed]
PHST- 1998/09/19 00:01 [medline]
PHST- 1998/09/19 00:00 [entrez]
AID - S0891-5849(98)00095-1 [pii]
AID - 10.1016/s0891-5849(98)00095-1 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 1998 Sep;25(4-5):392-403. doi: 
      10.1016/s0891-5849(98)00095-1.