Linked Life Data

7293234

Source:http://linkedlifedata.com/resource/pubmed/id/7293234

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1981-12-15
pubmed:abstractText
1. Four non-acidic primary metabolites of N-(5-pyrrolidinopent-3-ynyl)succinimide (BL 14) were identified and quantified using g.l.c. and mass spectrometry. The metabolites are alpha-hydroxy-N-(5-pyrrolidinopent-3-ynyl)succinimide (A), N-(5-(2-oxopyrrolidino)-pent-3-ynyl)succinimide (B), N-(2-hydroxy-5-pyrrolidinopent-3-ynyl)succinimide (C) and N-(5-pyrrolidinopent-3-ynyl)succinimide N-oxide (E), the latter analysed after reduction to the parent amine. 2. In rat liver preparations, all metabolites are formed by microsomal, NADPH-dependent enzyme systems, but with different characteristics. The response to inhibitors such as CO and SKF 525A indicates participation of cytochrome P-450 enzymes in the formation of all metabolites. Phenobarbital pretreatment markedly enhances propynylic hydroxylation (C) but has little or no effect on the other metabolic pathways. Succinimide hydroxylation (A) exhibits a pH optimum at 7.0, while the formation of metabolism B and C increases at pH values between 6.4 and 7.7. 3. Kinetic studies on the formation of metabolites A-C revealed differences in the Michaelis constant, while the Vmax values were similar. Succinimide hydroxylation (A) is most efficient with a Km of 3.7 X 10(-5) M, compared with a Km of 1.7 X 10(-3) M for propynylic hydroxylation (C). 4. The formation of metabolites B and E conforms to the corresponding mechanisms for lactam and N-oxide formation for other xenobiotics. The formation of metabolites A and C represents two extremities, reflected in their different responses to phenobarbital pretreatment, pH changes and in their different Km values. Although little can be discerned about the mechanisms from the literature, the enzymes catalysing both reactions appear to be cytochromes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0049-8254
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
459-71
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1981
pubmed:articleTitle
Metabolism of N-(5-pyrrolidinopent-3-ynyl)-succinimide (BL 14) in rat liver preparations. Characterization of four oxidative reactions.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't