Hepatic alteration of tryptophan metabolism in an acute porphyria model. Its relation with gluconeogenic blockage
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 comb...
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2008
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| LEADER | 15939caa a22015377a 4500 | ||
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| 001 | PAPER-6112 | ||
| 003 | AR-BaUEN | ||
| 005 | 20230518203547.0 | ||
| 008 | 190411s2008 xx ||||fo|||| 00| 0 eng|d | ||
| 024 | 7 | |2 scopus |a 2-s2.0-38049056756 | |
| 024 | 7 | |2 cas |a 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester, 12772-36-0, 632-93-9; 5 aminolevulinate synthase, 9037-14-3; allylisopropylacetamide, 299-78-5; ferrochelatase, 9012-93-5; heme, 14875-96-8; kynurenine, 16055-80-4, 343-65-7; phosphoenolpyruvate carboxykinase (GTP), 9013-08-5; porphobilinogen, 487-90-1; quinolinic acid, 89-00-9; serotonin, 50-67-9; tryptophan 2,3 dioxygenase, 9014-51-1; 5-Aminolevulinate Synthetase, EC 2.3.1.37; Allylisopropylacetamide, 299-78-5; Dicarbethoxydihydrocollidine, 632-93-9; Phosphoenolpyruvate Carboxykinase (ATP), EC 4.1.1.49; Tryptophan, 73-22-3 | |
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| 030 | |a BCPCA | ||
| 100 | 1 | |a Lelli, S.M. | |
| 245 | 1 | 0 | |a Hepatic alteration of tryptophan metabolism in an acute porphyria model. Its relation with gluconeogenic blockage |
| 260 | |c 2008 | ||
| 270 | 1 | 0 | |m San Martín de Viale, L.C.; Laboratorio de Disturbios Metabolicos por Xenobioticos, Salud Humana y Medio Ambiente (DIMXSA), Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pab. II, C1428EGA, Ciudad Autonoma de Buenos Aires, Argentina; email: dimxsa@qb.fcen.uba.ar |
| 506 | |2 openaire |e Política editorial | ||
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| 520 | 3 | |a 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. © 2007 Elsevier Inc. All rights reserved. |l eng | |
| 536 | |a Detalles de la financiación: Universidad de Buenos Aires | ||
| 536 | |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas | ||
| 536 | |a Detalles de la financiación: We thank Miss Juliana Rodriguez for her technical assistance in some experiments, and Dr. Elena Llambías for providing the tryptophan metabolites. This work was supported by grants from the Universidad de Buenos Aires (UBA) and the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Dr. L.C. San Martín de Viale is a Scientific Research Career Member of the CONICET. | ||
| 593 | |a Laboratorio de Disturbios Metabolicos por Xenobioticos, Salud Humana y Medio Ambiente (DIMXSA), Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pab. II, C1428EGA, Ciudad Autonoma de Buenos Aires, Argentina | ||
| 690 | 1 | 0 | |a 2-ALLYL-2-ISOPROPYLACETAMIDE |
| 690 | 1 | 0 | |a 3,5-DIETHOXYCARBONYL-1,4-DIHYDROCOLLIDINE |
| 690 | 1 | 0 | |a ACUTE PORPHYRIA MODEL |
| 690 | 1 | 0 | |a PHOSPHOENOLPYRUVATE-CARBOXYKINASE |
| 690 | 1 | 0 | |a TRYPTOPHAN METABOLISM |
| 690 | 1 | 0 | |a TRYPTOPHAN PYRROLASE |
| 690 | 1 | 0 | |a 1,4 DIHYDRO 2,4,6 TRIMETHYL 3,5 PYRIDINEDICARBOXYLIC ACID DIETHYL ESTER |
| 690 | 1 | 0 | |a 5 AMINOLEVULINATE SYNTHASE |
| 690 | 1 | 0 | |a ALLYLISOPROPYLACETAMIDE |
| 690 | 1 | 0 | |a FERROCHELATASE |
| 690 | 1 | 0 | |a HEME |
| 690 | 1 | 0 | |a KYNURENINE |
| 690 | 1 | 0 | |a PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP) |
| 690 | 1 | 0 | |a PORPHOBILINOGEN |
| 690 | 1 | 0 | |a QUINOLINIC ACID |
| 690 | 1 | 0 | |a SEROTONIN |
| 690 | 1 | 0 | |a THIOBARBITURIC ACID REACTIVE SUBSTANCE |
| 690 | 1 | 0 | |a TRYPTOPHAN 2,3 DIOXYGENASE |
| 690 | 1 | 0 | |a ANIMAL CELL |
| 690 | 1 | 0 | |a ANIMAL EXPERIMENT |
| 690 | 1 | 0 | |a ANIMAL MODEL |
| 690 | 1 | 0 | |a ANIMAL TISSUE |
| 690 | 1 | 0 | |a ARTICLE |
| 690 | 1 | 0 | |a CONTROLLED STUDY |
| 690 | 1 | 0 | |a DISEASE COURSE |
| 690 | 1 | 0 | |a DOSE RESPONSE |
| 690 | 1 | 0 | |a ENZYME ACTIVITY |
| 690 | 1 | 0 | |a FEMALE |
| 690 | 1 | 0 | |a LIVER METABOLISM |
| 690 | 1 | 0 | |a LIVER MICROSOME METABOLISM |
| 690 | 1 | 0 | |a LIVER TOXICITY |
| 690 | 1 | 0 | |a NONHUMAN |
| 690 | 1 | 0 | |a PORPHYRIA |
| 690 | 1 | 0 | |a PRIORITY JOURNAL |
| 690 | 1 | 0 | |a RAT |
| 690 | 1 | 0 | |a SEROTONINERGIC TRANSMISSION |
| 690 | 1 | 0 | |a TRYPTOPHAN METABOLISM |
| 690 | 1 | 0 | |a 5-AMINOLEVULINATE SYNTHETASE |
| 690 | 1 | 0 | |a ACUTE DISEASE |
| 690 | 1 | 0 | |a ALLYLISOPROPYLACETAMIDE |
| 690 | 1 | 0 | |a ANIMALS |
| 690 | 1 | 0 | |a DICARBETHOXYDIHYDROCOLLIDINE |
| 690 | 1 | 0 | |a DOSE-RESPONSE RELATIONSHIP, DRUG |
| 690 | 1 | 0 | |a FEMALE |
| 690 | 1 | 0 | |a LIVER |
| 690 | 1 | 0 | |a PHOSPHOENOLPYRUVATE CARBOXYKINASE (ATP) |
| 690 | 1 | 0 | |a PORPHYRIAS |
| 690 | 1 | 0 | |a RATS |
| 690 | 1 | 0 | |a RATS, WISTAR |
| 690 | 1 | 0 | |a TRYPTOPHAN |
| 650 | 1 | 7 | |2 spines |a GLUCONEOGENESIS |
| 650 | 1 | 7 | |2 spines |a GLUCONEOGENESIS |
| 700 | 1 | |a Mazzetti, M.B. | |
| 700 | 1 | |a San Martín de Viale, L.C. | |
| 773 | 0 | |d 2008 |g v. 75 |h pp. 704-712 |k n. 3 |p Biochem. Pharmacol. |x 00062952 |w (AR-BaUEN)CENRE-914 |t Biochemical Pharmacology | |
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