Linked Life Data

10037484

Source:http://linkedlifedata.com/resource/pubmed/id/10037484

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-3-18
pubmed:abstractText
The use of o-methoxybenzoylalanine, a selective kynureninase inhibitor, has been proposed with the aim of reducing brain synthesis of quinolinic acid, an excitotoxic tryptophan metabolite. In liver homogenates, however, this compound caused unexpected accumulation of 3-hydroxyanthranilic acid, the product of kynureninase activity and the precursor of quinolinic acid. To explain this observation, we investigated the interaction(s) of o-methoxybenzoylalanine with 3-hydroxyanthranilic acid dioxygenase, the enzyme responsible for quinolinic acid formation. When the purified enzyme or partially purified cytosol preparations were used, o-methoxybenzoylalanine did not affect 3-hydroxyanthranilic acid dioxygenase activity. However, a significant reduction of this enzymatic activity did occur when o-methoxybenzoylalanine was tested in the presence of mitochondria. It is interesting that addition of purified mitochondria to 3-hydroxyanthranilic acid dioxygenase preparations reduced the enzymatic activity and the synthesis of quinolinic acid. In vivo, administration of o-methoxybenzoylalanine significantly reduced quinolinic acid synthesis and content in both blood and brain of mice. Our results suggest that mitochondrial protein(s) interact(s) with soluble 3-hydroxyanthranilic acid dioxygenase and cause(s) modifications in the enzyme resulting in a decrease in its activity. These modifications also allow the enzyme to interact with o-methoxybenzoylalanine, thus leading to a further reduction in quinolinic acid synthesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2-methoxybenzoylalanine, http://linkedlifedata.com/resource/pubmed/chemical/3-Hydroxyanthranilate..., http://linkedlifedata.com/resource/pubmed/chemical/3-Hydroxyanthranilic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Alanine, http://linkedlifedata.com/resource/pubmed/chemical/Dioxygenases, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Hydrolases, http://linkedlifedata.com/resource/pubmed/chemical/Kynurenine, http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate, http://linkedlifedata.com/resource/pubmed/chemical/Oxygenases, http://linkedlifedata.com/resource/pubmed/chemical/Quinolinic Acid, http://linkedlifedata.com/resource/pubmed/chemical/kynureninase
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1125-32
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Effects of mitochondria and o-methoxybenzoylalanine on 3-hydroxyanthranilic acid dioxygenase activity and quinolinic acid synthesis.
pubmed:affiliation
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't