Linked Life Data

10574920

Source:http://linkedlifedata.com/resource/pubmed/id/10574920

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2000-2-3
pubmed:abstractText
Prior spin trapping studies reported that H(2)O(2) is metabolized by copper,zinc-superoxide dismutase (SOD) to form (.)OH that is released from the enzyme, serving as a source of oxidative injury. Although this mechanism has been invoked in a number of diseases, controversy remains regarding whether the hydroxylation of spin traps by SOD is truly derived from free (.)OH or (.)OH scavenged off the Cu(2+) catalytic site. To distinguish whether (.)OH is released from the enzyme, a comprehensive EPR investigation of radical production and the kinetics of spin trapping was performed in the presence of a series of structurally different (.)OH scavengers including ethanol, formate, and azide. Although each of these have similar potency in scavenging (.)OH as the spin trap 5, 5-dimethyl-1-pyrroline-N-oxide and form secondary radical adducts, each exhibited very different potency in scavenging (.)OH from SOD. Ethanol was 1400-fold less potent than would be expected for reaction with free (.)OH. The anionic scavenger formate, which readily accesses the active site, was still 10-fold less effective than would be predicted for free (.)OH, whereas azide was almost 2-fold more potent than would be predicted. Analysis of initial rates of adduct formation indicated that these reactions did not involve free (.)OH. EPR studies of the copper center demonstrated that while high H(2)O(2) concentrations induce release of Cu(2+), the magnitude of spin adducts produced by free Cu(2+) was negligible compared with that from intact SOD. Further studies with a series of peroxidase substrates demonstrated that characteristic radicals formed by peroxidases were also efficiently generated by H(2)O(2) and SOD. Thus, SOD and H(2)O(2) oxidize and hydroxylate substrates and spin traps through a peroxidase reaction with bound (.)OH not release of (.)OH from the enzyme.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2,2-dimethyl-5-hydroxy-1-pyrrolidiny..., http://linkedlifedata.com/resource/pubmed/chemical/5-diethoxyphosphoryl-5-methyl-1-pyrr..., http://linkedlifedata.com/resource/pubmed/chemical/Azides, http://linkedlifedata.com/resource/pubmed/chemical/Copper, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic N-Oxides, http://linkedlifedata.com/resource/pubmed/chemical/Ethanol, http://linkedlifedata.com/resource/pubmed/chemical/Formic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyl Radical, http://linkedlifedata.com/resource/pubmed/chemical/Iron, http://linkedlifedata.com/resource/pubmed/chemical/Peroxidase, http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase, http://linkedlifedata.com/resource/pubmed/chemical/formic acid
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34576-83
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Evidence against the generation of free hydroxyl radicals from the interaction of copper,zinc-superoxide dismutase and hydrogen peroxide.
pubmed:affiliation
Molecular and Cellular Biophysics Laboratories, Department of Medicine, Division of Cardiology, Electron Paramagnetic Resonance Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21224, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't