Linked Life Data

5378376

Source:http://linkedlifedata.com/resource/pubmed/id/5378376

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1970-5-4
pubmed:abstractText
1. The kinetics of the reaction of di-(2-chloroethyl) 3-chloro-4-methylcoumarin-7-yl phosphate (haloxon) and related compounds with acetylcholinesterase were studied and found to be unusual. 2. By a progressive reaction haloxon produces a di-(2-chloroethyl)phosphorylated enzyme. The influence of substrate on this reaction leading to a phosphorylated active centre was studied. From competition experiments between inhibitor and substrate values of K(m) for acetylcholine and acetylthiocholine of 0.79mm and 0.23mm respectively were derived. 3. Haloxon also combines with acetylcholinesterase by a non-progressive reaction, producing a complex that is reversible by dilution and by high concentrations of acetylcholine and acetylthiocholine. From this non-progressive reaction the competition between haloxon and substrate was studied, and it was shown that haloxon combines with a site involved in inhibition by substrate. From competition experiments the following dissociation constants were derived: for combination of haloxon and this site K(i) is 4.9mum and for the combination of substrates with this site K(88) values are 12mm and 3.3mm for acetylcholine and acetylthiocholine respectively. 4. The non-phosphorus-containing compound 3-chloro-7-hydroxy-4-methylcoumarin was shown to be a good reagent for the site involved in inhibition by substrate; its dissociation constant for the combination with this site is 30mum. 5. In order to interpret the experimental results, theoretical equations were derived for an enzyme with two binding sites to both of which substrate and inhibitor can combine. The equations correlate the activity of the enzyme with the concentration of substrate and inhibitor, for both progressive and non-progressive inhibition. These equations are applicable to reactions of acetylcholinesterase with organophosphorus compounds, carbamates etc. and may be applicable to other enzymes possessing two binding sites.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/5378376-13018298, http://linkedlifedata.com/resource/pubmed/commentcorrection/5378376-13066454, http://linkedlifedata.com/resource/pubmed/commentcorrection/5378376-13726518, http://linkedlifedata.com/resource/pubmed/commentcorrection/5378376-13785321, http://linkedlifedata.com/resource/pubmed/commentcorrection/5378376-14078913, http://linkedlifedata.com/resource/pubmed/commentcorrection/5378376-14137949, http://linkedlifedata.com/resource/pubmed/commentcorrection/5378376-14248384, http://linkedlifedata.com/resource/pubmed/commentcorrection/5378376-14784953, http://linkedlifedata.com/resource/pubmed/commentcorrection/5378376-15420172, http://linkedlifedata.com/resource/pubmed/commentcorrection/5378376-16747599, http://linkedlifedata.com/resource/pubmed/commentcorrection/5378376-6053593, http://linkedlifedata.com/resource/pubmed/commentcorrection/5378376-6070126
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0264-6021
pubmed:author
pubmed:issnType
Print
pubmed:volume
115
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
147-62
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1969
pubmed:articleTitle
Acetylcholinesterase. Two types of inhibition by an organophosphorus compound: one the formation of phosphorylated enzyme and the other analogous to inhibition by substrate.
pubmed:publicationType
Journal Article