Linked Life Data

3965709

Source:http://linkedlifedata.com/resource/pubmed/id/3965709

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1985-2-14
pubmed:abstractText
N-Arylhydroxamic acid N,O-acyltransferase (AHAT) catalyzes the transfer of the N-acetyl group from N-arylhydroxamic acids to arylamines. In the absence of an arylamine acceptor, AHAT catalyzes the conversion of N-arylhydroxamic acids to reactive electrophilic intermediates that become irreversibly bound to cellular nucleophiles, including those present on AHAT itself. As part of an investigation of the AHAT-catalyzed bioactivation process, a series of 7-substituted analogues of N-hydroxy-2-acetamidofluorene (1) was synthesized and evaluated in vitro as substrates and inactivators of a partially purified hamster hepatic AHAT preparation. All of the compounds functioned as acetyl donors in the AHAT-catalyzed transacetylation of 4-aminoazobenzene (AAB) and all of them were inactivators of AHAT. The inactivation process exhibited apparent first-order kinetics, and the 7-methoxy compound exhibited the largest inactivation rate constant. Quantitative structure-activity analysis provided support for the concept that positively charged species are involved in the inactivation of AHAT by this series of compounds. Results of experiments in which nucleophilic trapping agents such as glutathione, cysteine, methionine, guanosine phosphate, and tRNA were included in incubation mixtures with AHAT and the N-arylhydroxamic acids indicated that electrophiles which diffuse away from the enzyme active site participate in the inactivation process.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18-24
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1985
pubmed:articleTitle
Mechanism-based inactivation of N-arylhydroxamic acid N,O-acyltransferase by 7-substituted-N-hydroxy-2-acetamidofluorenes.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.