PMID- 10512739
OWN - NLM
STAT- MEDLINE
DCOM- 19991123
LR  - 20141120
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 263
IP  - 3
DP  - 1999 Oct 5
TI  - Oxidation of tetrahydrobiopterin by peroxynitrite: implications for vascular
      endothelial function.
PG  - 681-4
AB  - Subsaturating levels of tetrahydrobiopterin (BH(4)), an essential cofactor for
      nitric oxide synthase (NOS), can lead to endothelial dysfunction as a result of
      decreased production of nitric oxide. Furthermore, insufficient BH(4) can also
      result in NOS-uncoupled production of reactive oxygen intermediates, such as
      superoxide anion and hydrogen peroxide. Nitric oxide and superoxide react rapidly
      to form peroxynitrite, which may be the reactive species responsible for many of 
      the toxic effects of nitric oxide. Here we show that BH(4) is a primary target
      for peroxynitrite-catalyzed oxidation because at pH 7.4, physiologically relevant
      concentrations of BH(4) are oxidized rapidly by low concentrations of
      peroxynitrite. Peroxynitrite oxidizes BH(4) to quinonoid 5,6-dihydrobiopterin and
      a large proportion of the quinonoid isomer readily loses its side chain to form
      7,8-dihydropterin which is not a cofactor for nitric oxide synthase. Thus,
      abnormally low levels of BH(4) can promote a cycle of its own destruction
      mediated by nitric oxide synthase-dependent formation of peroxynitrite. This
      mechanism might contribute to vascular endothelial dysfunction induced by
      oxidative stress.
CI  - Copyright 1999 Academic Press.
FAU - Milstien, S
AU  - Milstien S
AD  - Laboratory of Cellular and Molecular Regulation, National Institute of Mental
      Health, Bethesda, Maryland 20892, USA. milstien@codon.nih.gov
FAU - Katusic, Z
AU  - Katusic Z
LA  - eng
GR  - HL-53542/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Antioxidants)
RN  - 0 (Nitrates)
RN  - 0 (Oxidants)
RN  - 0 (Pteridines)
RN  - 22150-76-1 (Biopterin)
RN  - 26404-66-0 (peroxynitric acid)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EGX657432I (sapropterin)
SB  - IM
MH  - Antioxidants/*chemistry
MH  - Biopterin/*analogs & derivatives/chemistry
MH  - Endothelium, Vascular/*physiology
MH  - Kinetics
MH  - Nitrates/*chemistry
MH  - Nitric Oxide Synthase/metabolism
MH  - Oxidants/*chemistry
MH  - Oxidation-Reduction
MH  - Pteridines/chemistry
EDAT- 1999/10/08 00:00
MHDA- 1999/10/08 00:01
CRDT- 1999/10/08 00:00
PHST- 1999/10/08 00:00 [pubmed]
PHST- 1999/10/08 00:01 [medline]
PHST- 1999/10/08 00:00 [entrez]
AID - 10.1006/bbrc.1999.1422 [doi]
AID - S0006-291X(99)91422-5 [pii]
PST - ppublish
SO  - Biochem Biophys Res Commun. 1999 Oct 5;263(3):681-4. doi: 10.1006/bbrc.1999.1422.