Linked Life Data

15520012

Source:http://linkedlifedata.com/resource/pubmed/id/15520012

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
50
pubmed:dateCreated
2004-12-6
pubmed:abstractText
Hydrogen sulfide (H2S) has been observed in relatively high concentrations in the mammalian brain and has been shown to act as a neuromodulator. However, there is confusion in the literature regarding the actual source of H2S production. Reactions catalyzed by the cystathionine beta-synthase enzyme (CBS) are one possible source for the production of H2S. Here we show that the CBS enzyme can efficiently produce H2S via a beta-replacement reaction in which cysteine is condensed with homocysteine to form cystathionine and H2S. The production of H2S by this reaction is at least 50 times more efficient than that produced by hydrolysis of cysteine alone via beta-elimination. Kinetic studies demonstrate that the Km and Kcat for cysteine is 3-fold higher and 2-fold lower, respectively, than that for serine. Consistent with these data, in vitro reconstitution studies show that at physiologically relevant concentrations of serine, homocysteine, and cysteine, about 5% of the cystathionine formed is from cysteine. We also show that AdoMet stimulates this H2S producing reaction but that there is no evidence for stimulation by calcium and calmodulin as reported previously. In summary, these results confirm the ability of CBS to produce H2S, but show in contrast to prior reports that the major mechanism is via beta-replacement and not cysteine hydrolysis. In addition, these studies provide a biochemical explanation for the previously inexplicable homocysteine-lowering effects of N-acetylcysteine treatments in humans.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
52082-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Production of the neuromodulator H2S by cystathionine beta-synthase via the condensation of cysteine and homocysteine.
pubmed:affiliation
Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't