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dc.contributor.author
Lelli, Sandra Marcela
dc.contributor.author
Mazzetti, Marta Blanca
dc.contributor.author
San Martin, Leonor Carmen
dc.date.available
2019-02-25T18:40:22Z
dc.date.issued
2008-02
dc.identifier.citation
Lelli, Sandra Marcela; Mazzetti, Marta Blanca; San Martin, Leonor Carmen; Hepatic alteration of tryptophan metabolism in an acute porphyria model. Its relation with gluconeogenic blockage; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 75; 3; 2-2008; 704-712
dc.identifier.issn
0006-2952
dc.identifier.uri
http://hdl.handle.net/11336/70801
dc.description.abstract
This study focuses on the alterations suffered by the serotoninergic and kinurenergic routes of tryptophan (TRP) metabolism in liver, and their relation with gluconeogenic phosphoenolpyruvate-carboxykinase (PEPCK) blockage in experimental acute porphyria. This porphyria was induced in rats by a combined treatment of 2-allyl-2-isopropylacetamide (100, 250, 500 mg/kg bw) and 3,5-dietoxicarbonil 1,4-dihydrocollidine (constant 50 mg/kg bw dose). Results showed a marked dose-dependent increase of all TRP pyrrolase (TRPp) forms, active (holo, total) and inactive (apo), and a decrease in the degree of enzyme saturation by heme. Increases for holo, total, and apo-TRPp were 90, 150, and 230%, respectively, at the highest dose assayed (H). The treatment also impaired the serotoninergic route of TRP metabolism in liver, causing a decrease in serotonin level (H, 38%), and a concomitant enhancement in TRP content (H, 23%). The porphyrinogenic treatment promoted a blockage in PEPCK activity (H, 30%). This occurred in correlation to the development of porphyria, to TRPp alterations and to the production of hepatic microsomal thiobarbituric acid reactive substances. Porphyria was estimated through increases in 5-aminolevulinic acid-synthase (ALA-S) activity, ALA and porphobilinogen contents, and a decrease in ferrochelatase activity. Thus, the TRP kynurenine route was augmented whereas the serotoninergic route was reduced. PEPCK blockage could be partly attributed to quinolinate generated from TRP by the increase of TRPp activity, which would be due to the effect of porphyrinogenic drugs on TRP. The contribution of ROS to PEPCK blockage is analyzed. Likewise, the implication of these results in the control of porphyrias by glucose is discussed.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
2-Allyl-2-Isopropylacetamide
dc.subject
3,5-Diethoxycarbonyl-1,4-Dihydrocollidine
dc.subject
Acute Porphyria Model
dc.subject
Phosphoenolpyruvate-Carboxykinase
dc.subject
Tryptophan Metabolism
dc.subject
Tryptophan Pyrrolase
dc.subject.classification
Otras Ciencias Biológicas
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Hepatic alteration of tryptophan metabolism in an acute porphyria model. Its relation with gluconeogenic blockage
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-02-12T17:10:10Z
dc.journal.volume
75
dc.journal.number
3
dc.journal.pagination
704-712
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Lelli, Sandra Marcela. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
dc.description.fil
Fil: Mazzetti, Marta Blanca. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
dc.description.fil
Fil: San Martin, Leonor Carmen. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title
Biochemical Pharmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bcp.2007.09.023
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0006295207006673
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