Linked Life Data

8605171

Source:http://linkedlifedata.com/resource/pubmed/id/8605171

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1996-5-21
pubmed:abstractText
Previous studies have established that 1-cyclopropyl-4-phenyl-1,2,3,6-tetrahydropyridine is an efficient time- and concentration-dependent inhibitor of the flavin-containing enzyme monoamine oxidase B (MAO-B). This behavior is consistent with a proposed mechanism-based inactivation pathway which proceeds via an initial single electron transfer step to generate an unstable cyclopropylaminyl radical cation intermediate that alkylates an active site functionality via the ring opened primary carbon centered radical. More recently we have found that, in addition to being an inhibitor, the corresponding 1-cyclopropyl-4-benzyl-1,2,3,6-tetrahydropyridine species is an excellent MAO-B substrate, behavior which may not be consistent with the obligatory formation of a cyclopropylaminyl radical cation intermediate. In an attempt to gain further insight into the mechanism associated with the MAO catalyzed oxidation of 1,4-disubstituted tetrahydropyridines, we have undertaken deuterium isotope effect studies on the substrate and inhibitor properties of this 4-benzyl-1-cyclopropyltetrahydropyridine derivative. A normal isotope effect was observed on kcat/KM. Although the good substrate properties of this compound prevented an accurate estimate of k(inact) and K1, we did observe a very modest inverse isotope effect on the rate of inactivation of 0.1 microM MAO-B by 500 microM inactivator. The results are discussed in terms of possible mechanisms for the MAO-B catalyzed oxidation of 1,4-disubstituted 1,2,3,6-tetrahydropyridines.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3335-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Deuterium isotope effect studies on the MAO-B catalyzed oxidation of 4-benzyl-1-cyclopropyl-1,2,3,6-tetrahydropyridine.
pubmed:affiliation
Department of Chemistry, Virginia Polytechnic Institute & State University, Blacksburg 24061, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't