Linked Life Data

16506790

Source:http://linkedlifedata.com/resource/pubmed/id/16506790

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2006-3-1
pubmed:abstractText
The highly basic heme enzyme myeloperoxidase (MPO), which is released by activated phagocytes, catalyzes the production of the potent oxidant hypochlorite (HOCl) from H(2)O(2) and chloride ions (Cl(-)). Heparan sulfate proteoglycans are key components of the extracellular matrix and cell surfaces and are known to bind MPO avidly via their negatively charged heparan sulfate chains. Reaction of heparan sulfate with HOCl generates polymer-derived N-chloro derivatives (chloramines, dichloramines, N-chlorosulfonamides, and chloramides). In this study, it is shown that heparan sulfate N-chloro derivatives are decomposed in the presence of redox-active transition-metal ions and superoxide (O(2)(*-)). These processes initiate polymer modification/fragmentation. Radical intermediates in these processes have been identified by EPR spectroscopy and spin trapping. Evidence has been obtained that the N-chloro derivatives undergo reductive homolysis to nitrogen-centered (aminyl, N-chloroaminyl, sulfonamidyl, and amidyl) radicals that generate carbon-centered radicals via rapid, intramolecular hydrogen atom abstraction reactions (1,2- and/or 1,5-shifts). In the case of the sulfonamidyl radicals, rearrangement via 1,2-shifts and beta-scission of the resultant C-2 carbon-centered radicals to yield SO(3)(*-) and C-2 imines is near quantitative based on the yield of SO(4)(2-), the decomposition product of SO(3)(*-). The formation of strand breaks and chromophores during these reactions is attributed to the formation and subsequent heterolytic rearrangement of the C-2 imines. The degradation of heparan sulfate via reductive homolysis of its N-chloro derivatives may be of significance at sites of inflammation, where MPO-derived HOCl is produced in high concentration and transition-metal ions and O(2)(*-) are known to be present or generated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0002-7863
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3085-97
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Heparan sulfate degradation via reductive homolysis of its N-chloro derivatives.
pubmed:affiliation
Heart Research Institute, 145-147 Missenden Road, Camperdown, Sydney NSW 2050, Australia.
pubmed:publicationType
Journal Article