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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1982-12-16
|
| pubmed:abstractText |
The microsomal fraction of ram seminal vesicles (RSV), when fortified with arachidonic acid, catalyzed the dealkylation of various N-methyl compounds. These included an analogous series of monomethyl- and dimethyl-substituted anilines as well as the drugs aminopyrine and benzphetamine. In contrast, S-alkyl and O-alkyl compounds were poor substrates for dealkylation by RSV microsomes fortified with fatty acid. RSV microsomal N-dealkylation was completely dependent on enzyme and arachidonic acid and could be inhibited by the prostaglandin synthetase inhibitors indomethacin, phenylbutazone, and flufenamic acid as well as by anaerobic conditions. Butylated hydroxyanisole also inhibited the reaction, whereas SKF-525A and metyrapone, which are inhibitors of cytochrome P-450-dependent N-dealkylation, did not. In addition to arachidonic acid, N-dealkylation was elicited by 15-hydroperoxyarachidonic acid, tert-butyl-hydroperoxide, and hydrogen peroxide; these latter reactions were not inhibited by either prostaglandin synthetase inhibitors or anaerobic conditions but did require the presence of microsomal protein. The time course of RSV N-dealkylation, which paralleled O2 consumption by this tissue (an indicator of prostaglandin biosynthesis) implied arachidonic acid-dependent irreversible self-inactivation of catalytic activity. Apparently, oxidizing agents are formed during the interaction of hydroperoxide intermediates of prostaglandin biosynthesis with prostaglandin synthetase, with the oxidizing agents then causing both substrate N-dealkylation and destruction of the enzyme. The metabolism of N-alkyl compounds during the biosynthesis of prostaglandins may provide an additional xenobiotic oxidation pathway to cytochrome P-450-dependent monooxygenases.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-chloro-N-methylaniline demethylase,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Indomethacin,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases, N-Demethylating,
http://linkedlifedata.com/resource/pubmed/chemical/Pharmaceutical Preparations,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0026-895X
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
21
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
133-41
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:6813675-Animals,
pubmed-meshheading:6813675-Arachidonic Acid,
pubmed-meshheading:6813675-Arachidonic Acids,
pubmed-meshheading:6813675-Dealkylation,
pubmed-meshheading:6813675-Female,
pubmed-meshheading:6813675-Guinea Pigs,
pubmed-meshheading:6813675-Indomethacin,
pubmed-meshheading:6813675-Kinetics,
pubmed-meshheading:6813675-Male,
pubmed-meshheading:6813675-Mice,
pubmed-meshheading:6813675-Mice, Inbred A,
pubmed-meshheading:6813675-Microsomes, Liver,
pubmed-meshheading:6813675-Oxidoreductases, N-Demethylating,
pubmed-meshheading:6813675-Pharmaceutical Preparations,
pubmed-meshheading:6813675-Prostaglandins,
pubmed-meshheading:6813675-Rabbits,
pubmed-meshheading:6813675-Rats,
pubmed-meshheading:6813675-Rats, Inbred Strains,
pubmed-meshheading:6813675-Seminal Vesicles,
pubmed-meshheading:6813675-Sheep
|
| pubmed:year |
1982
|
| pubmed:articleTitle |
Metabolism of N-alkyl compounds during the biosynthesis of prostaglandins. N-Dealkylation during prostaglandin biosynthesis.
|
| pubmed:publicationType |
Journal Article,
In Vitro
|