Linked Life Data

19821602

Source:http://linkedlifedata.com/resource/pubmed/id/19821602

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2009-11-17
pubmed:abstractText
Hypothiocyanite is a major oxidant generated by mammalian peroxidases. Although reported to react specifically with thiol groups in biological molecules, a detailed mechanistic study of this reaction has not been conducted. We have investigated the reaction of hypothiocyanous acid/hypothiocyanite with 5-thio-2-nitrobenzoic acid and with reduced glutathione by stopped-flow spectroscopy. The observed bell-shaped pH profile established that the reaction with 5-thio-2-nitrobenzoic acid proceeds via the thiolate and hypothiocyanous acid in the 2.5 < pH < 8 region. The obtained second-order rate constant of the reaction is (1.26 + or - 0.02) x 10(8) M(-1) s(-1), and the effective rate constant at pH 7.4 is (4.37 + or - 0.03) x 10(5) M(-1) s(-1). Analysis of the kinetic data, using a value of 4.38 + or - 0.01 for the pK(a) of 5-thio-2-nitrobenzoic acid thiol (measured independently by spectroscopic analysis), gave a pK(a) of 4.85 + or - 0.01 for hypothiocyanous acid at physiological salt concentration (I = 120 mM; NaCl and phosphate buffer) and 25 degrees C. A second-order rate constant of (8.0 + or - 0.5) x 10(4) M(-1) s(-1) for the reaction of hypothiocyanous acid/hypothiocyanite with reduced glutathione at pH 7.4 was determined. The glutathione data are also consistent with the reaction proceeding via the thiolate and hypothiocyanous acid. Our results demonstrate that hypothiocyanous acid/hypothiocyanite has very high reactivity with thiols and will be short-lived in the presence of physiological concentrations of glutathione and thiol proteins. As the reaction occurs strictly with the thiolate, this oxidant should selectively target proteins containing low pK(a) thiols.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1520-5010
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1833-40
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Kinetics and mechanisms of the reaction of hypothiocyanous acid with 5-thio-2-nitrobenzoic acid and reduced glutathione.
pubmed:affiliation
Department of Pathology, University of Otago Christchurch, P.O. Box 4345, Christchurch, New Zealand. peter.nagy@otago.ac.nz
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't