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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2000-5-9
pubmed:abstractText
o-Methoxybenzoylalanine, a selective kynureninase inhibitor, caused unexpected accumulation of 3-hydroxyanthranilic acid (3OH-ANA), the product of kynureninase activity and the precursor of quinolinic acid (QUIN) in liver homogenates incubated with 3OH-kynurenine (3OH-KYN). In order to explain this observation, we investigated the interaction(s) of o-methoxybenzoylalanine with 3-hydroxyanthranilic acid dioxygenase, the enzyme responsible of QUIN formation. When the purified enzyme, or partially purified cytosol preparations were used, oMBA did not affect 3-hydroxyanthranilic acid dioxygenase activity. The addition of purified mitochondria to 3-hydroxyanthranilic acid dioxygenase preparations reduced the enzymatic activity and the synthesis of QUIN. In the presence of mitochondria oMBA further reduced QUIN synthesis. The administration of oMBA reduced QUIN 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 oMBA, thus leading to a further reduction in QUIN synthesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0065-2598
pubmed:author
pubmed:issnType
Print
pubmed:volume
467
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
233-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Regulation of quinolinic acid synthesis by mitochondria and o-methoxybenzoylalanine.
pubmed:affiliation
Department of Preclinical and Clinical Pharmacology, University of Florence, Firenze, Italy.
pubmed:publicationType
Journal Article, In Vitro, Review