Linked Life Data

10036217

Source:http://linkedlifedata.com/resource/pubmed/id/10036217

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-3-16
pubmed:abstractText
Inhibition of acetylcholinesterase (AChE) by isomalathion has been assumed to proceed by expulsion of diethyl thiosuccinyl to produce O, S-dimethyl phosphorylated AChE. If this assumption is correct, AChE inhibited by (1R)- or (1S)-isomalathions should reactivate at the same rate as AChE inhibited by configurationally equivalent (S)- or (R)-isoparathion methyl, respectively, which are expected to inhibit AChE by loss of 4-nitrophenoxyl to yield O,S-dimethyl phosphorylated AChEs. Previous work has shown that rat brain AChE inhibited by (1R)-isomalathions reactivates at the same rate as the enzyme inhibited by (S)-isoparathion methyl. However, although rat brain AChE inhibited by (R)-isoparathion methyl reactivates at a measurable rate, the enzyme inhibited by (1S)-isomalathions is intractable to reactivation. This surprising finding suggests the hypothesis that (1R)- and (1S)-stereoisomers of isomalathion inhibit AChE by different mechanisms, yielding enzymatic species distinguishable by their postinhibitory kinetics. The present study was carried out to test this hypothesis by comparing kinetic constants of reactivation (k+3) and aging (k+4) of hen brain AChE and bovine erythrocyte AChE inhibited by the four stereoisomers of isomalathion and the two stereoisomers of isoparathion methyl. Both AChEs inhibited by either (1R,3R)- or (1R,3S)-isomalathion had comparable corresponding k+3 values (spontaneous and oxime-mediated) to those of AChEs inhibited with (S)-isoparathion methyl. However, spontaneous and oxime-mediated k+3 values comparable to those of (R)-isoparathion methyl could not be obtained for AChEs inhibited by (1S,3R)- and (1S,3S)-isomalathion. Comparison of k+4 values for hen brain AChE inhibited by each stereoisomer of isomalathion and isoparathion methyl corroborated that only the (1S)-isomalathions failed to produce the expected O,S-dimethyl phosphoryl-conjugated enzymes. The results for (1R)-isomalathions suggest that the mechanism of inhibition of AChE by these isomers is the expected one involving diethyl thiosuccinyl as the primary leaving group. In contrast, the results for (1S)-isomalathions are consistent with an alternative mechanism of inhibition by these isomers implicating loss of thiomethyl as the primary leaving group.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0041-008X
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
155
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
43-53
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Kinetic evidence for different mechanisms of acetylcholinesterase inhibition by (1R)- and (1S)-stereoisomers of isomalathion.
pubmed:affiliation
Department of Environmental & Industrial Health, The University of Michigan, Ann Arbor, Michigan, 48109, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't