Title: Kinetics of the anaerobic reaction of nitric oxide with cysteine, glutathione and cysteine-containing proteins: implications for in vivo S-nitrosation
Authors: Aravindakumar, CT ×
De Ley, Marc
Ceulemans, Jan #
Issue Date: Jan-2002
Publisher: Royal soc chemistry
Series Title: Journal of the chemical society-perkin transactions 2 issue:3 pages:663-669
Abstract: A study is made of the kinetics of the anaerobic reaction of nitric oxide ((NO)-N-.) with cysteine and glutathione in relation to its potential physiological importance for the S-nitrosation of cysteine-containing peptides and proteins. The kinetics of the reaction with cysteine (the basic reagent unit) is studied most extensively and it is found that the rate constant is directly proportional to the degree of ionization (a), k = 0.37 x 10(3)a M-1 s(-1), offering clear proof for a mechanism based on electrophilic attack of (NO)-N-. on thiolate anions. The rate constant for glutathione is considerably lower than for cysteine at identical pH, which can be attributed to its higher pK(a); steric effects do not appear to affect the reactivity of glutathione significantly. On the basis of the rate equations obtained and of similar data for bovine serum albumin and metallothionein-1 a number of calculations were performed with the aim of determining the relative importance of the reaction of (NO)-N-. with O-2 vs. the direct reaction of (NO)-N-. with peptide and protein thiols under in vivo conditions. The results clearly show that in cells that as a rule contain an appreciable concentration of glutathione the autoxidation of (NO)-N-. and thus the reaction of higher oxides of nitrogen ((NO2)-N-., N2O3) with thiol groups in peptides and proteins does not play a role of any significance with respect to the formation of S-nitrosothiols, as the direct reaction of (NO)-N-. with the thiolate group in glutathione leading to the formation of GS-(NO-)-N-. is much faster than the reaction of (NO)-N-. with O-2. The difference in reactivity is less pronounced in the case of bovine serum albumin, but again the electrophilic attack clearly is more important than the autoxidation at most physiological (NO)-N-. concentrations. Direct electrophilic attack of (NO)-N-. on metallothionein is of no practical significance, as the process is very much slower than the attack on glutathione.
ISSN: 1472-779X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Biochemistry, Molecular and Structural Biology Section
Quantum Chemistry and Physical Chemistry Section
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science