Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1999-6-10
pubmed:abstractText
The metabolite glutathione fulfills many important and chemically complex roles in protecting cellular components from the deleterious effects of toxic species. GSH combines with hydroxyl radical, peroxynitrite, and hydroperoxides, as well as reactive electrophiles, including activated phosphoramide mustard. This thiol-containing reductant also maintains so-called thiol-enzymes in their catalytically active form, and maintains vitamins C and E in their biologically active forms. The key step in glutathione synthesis, namely the ATP-dependent synthesis of gamma-glutamylcysteine, is the topic of this review. Details are presented on (a) the enzyme's purification and protein chemistry, (b) the successful cDNA cloning, and characterization of the genes responsible for the biosynthesis of this enzyme. After considering aspects of the role of overexpression of this synthetase in terms of cancer chemotherapy, attention is focused on post-translational regulation. The remainder of the review deals with the catalytic mechanism (including substrate specificity, reactions catalyzed, steady-state kinetics, and chemical mechanism) as well as the inhibition of the enzyme (via feedback inhibition, reaction with S-alkyl homocysteine sulfoximine inhibitors, the clinical use of buthionine sulfoximine with cancer patients, and inactivation by cystamine, chloroketones, and various nitric oxide donors).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0065-258X
pubmed:author
pubmed:issnType
Print
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
209-67, xii
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
The enzymes of glutathione synthesis: gamma-glutamylcysteine synthetase.
pubmed:affiliation
Department of Biochemistry, Medical College of Wisconsin, Milwaukee 53226, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review