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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
47
pubmed:dateCreated
1996-1-17
pubmed:abstractText
Nitrosothiols are powerful vasodilators. They act by releasing nitric oxide, which activates the heme protein guanylate cyclase. We have studied the kinetics of nitrosothiol formation of glutathione, cysteine, N-acetylcysteine, human serum albumin, and bovine serum albumin upon reaction with nitric oxide (NO) in the presence of oxygen. These studies have been made at low pH as well as at physiological pH. At pH 7.0, contrary to published reports, nitric oxide by itself does not react with thiols to yield nitrosothiol. However, formation of nitrosothiols is observed in the presence of oxygen. For all thiols studied, the rates of nitrosothiol formation were first order in O2 concentration and second order in NO concentration and at lower concentrations (< 5 mM thiol) also depended on thiol concentrations. Analysis of the kinetic data indicated that the rate-limiting step was the reaction of NO with oxygen. Analysis of the reaction products suggest that the main nitrosating species is N2O3: RSH+N2O3-->RSNO+NO2- + H+. Rate constants for this reaction for glutathione and several other low molecular weight thiols are in the range of 3-1.5 x 10(5) M-1 s-1, and for human and bovine serum albumins 0.3 x 10(5) M-1 s-1 and 0.06 x 10(5) M-1 s-1, respectively. The data further indicate that the reaction rate of the nitrosating species N2O3 with thiols is competitive with its rate of hydrolysis. At physiological concentrations nitrosoglutathione formation represents a significant metabolic fate of N2O3, and at glutathione concentrations of 5 mM or higher almost all of N2O3 formed is consumed in nitrosation of glutathione. Implications of these results for in vivo nitrosation of thiols are discussed.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28158-64
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Kinetics of nitrosation of thiols by nitric oxide in the presence of oxygen.
pubmed:affiliation
Department of Medicine, University of California, San Diego, La Jolla 92093-0652, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.