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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todo:paper_00062952_v75_n3_p704_Lelli2023-10-03T14:04:19Z Hepatic alteration of tryptophan metabolism in an acute porphyria model. Its relation with gluconeogenic blockage Lelli, S.M. Mazzetti, M.B. San Martín de Viale, L.C. 2-Allyl-2-isopropylacetamide 3,5-Diethoxycarbonyl-1,4-dihydrocollidine Acute porphyria model Phosphoenolpyruvate-carboxykinase Tryptophan metabolism Tryptophan pyrrolase 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester 5 aminolevulinate synthase allylisopropylacetamide ferrochelatase heme kynurenine phosphoenolpyruvate carboxykinase (GTP) porphobilinogen quinolinic acid serotonin thiobarbituric acid reactive substance tryptophan 2,3 dioxygenase animal cell animal experiment animal model animal tissue article controlled study disease course dose response enzyme activity female gluconeogenesis liver metabolism liver microsome metabolism liver toxicity nonhuman porphyria priority journal rat serotoninergic transmission tryptophan metabolism 5-Aminolevulinate Synthetase Acute Disease Allylisopropylacetamide Animals Dicarbethoxydihydrocollidine Dose-Response Relationship, Drug Female Gluconeogenesis Liver Phosphoenolpyruvate Carboxykinase (ATP) Porphyrias Rats Rats, Wistar Tryptophan 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. Fil:Lelli, S.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Mazzetti, M.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:San Martín de Viale, L.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00062952_v75_n3_p704_Lelli |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
2-Allyl-2-isopropylacetamide 3,5-Diethoxycarbonyl-1,4-dihydrocollidine Acute porphyria model Phosphoenolpyruvate-carboxykinase Tryptophan metabolism Tryptophan pyrrolase 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester 5 aminolevulinate synthase allylisopropylacetamide ferrochelatase heme kynurenine phosphoenolpyruvate carboxykinase (GTP) porphobilinogen quinolinic acid serotonin thiobarbituric acid reactive substance tryptophan 2,3 dioxygenase animal cell animal experiment animal model animal tissue article controlled study disease course dose response enzyme activity female gluconeogenesis liver metabolism liver microsome metabolism liver toxicity nonhuman porphyria priority journal rat serotoninergic transmission tryptophan metabolism 5-Aminolevulinate Synthetase Acute Disease Allylisopropylacetamide Animals Dicarbethoxydihydrocollidine Dose-Response Relationship, Drug Female Gluconeogenesis Liver Phosphoenolpyruvate Carboxykinase (ATP) Porphyrias Rats Rats, Wistar Tryptophan |
spellingShingle |
2-Allyl-2-isopropylacetamide 3,5-Diethoxycarbonyl-1,4-dihydrocollidine Acute porphyria model Phosphoenolpyruvate-carboxykinase Tryptophan metabolism Tryptophan pyrrolase 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester 5 aminolevulinate synthase allylisopropylacetamide ferrochelatase heme kynurenine phosphoenolpyruvate carboxykinase (GTP) porphobilinogen quinolinic acid serotonin thiobarbituric acid reactive substance tryptophan 2,3 dioxygenase animal cell animal experiment animal model animal tissue article controlled study disease course dose response enzyme activity female gluconeogenesis liver metabolism liver microsome metabolism liver toxicity nonhuman porphyria priority journal rat serotoninergic transmission tryptophan metabolism 5-Aminolevulinate Synthetase Acute Disease Allylisopropylacetamide Animals Dicarbethoxydihydrocollidine Dose-Response Relationship, Drug Female Gluconeogenesis Liver Phosphoenolpyruvate Carboxykinase (ATP) Porphyrias Rats Rats, Wistar Tryptophan Lelli, S.M. Mazzetti, M.B. San Martín de Viale, L.C. Hepatic alteration of tryptophan metabolism in an acute porphyria model. Its relation with gluconeogenic blockage |
topic_facet |
2-Allyl-2-isopropylacetamide 3,5-Diethoxycarbonyl-1,4-dihydrocollidine Acute porphyria model Phosphoenolpyruvate-carboxykinase Tryptophan metabolism Tryptophan pyrrolase 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester 5 aminolevulinate synthase allylisopropylacetamide ferrochelatase heme kynurenine phosphoenolpyruvate carboxykinase (GTP) porphobilinogen quinolinic acid serotonin thiobarbituric acid reactive substance tryptophan 2,3 dioxygenase animal cell animal experiment animal model animal tissue article controlled study disease course dose response enzyme activity female gluconeogenesis liver metabolism liver microsome metabolism liver toxicity nonhuman porphyria priority journal rat serotoninergic transmission tryptophan metabolism 5-Aminolevulinate Synthetase Acute Disease Allylisopropylacetamide Animals Dicarbethoxydihydrocollidine Dose-Response Relationship, Drug Female Gluconeogenesis Liver Phosphoenolpyruvate Carboxykinase (ATP) Porphyrias Rats Rats, Wistar Tryptophan |
description |
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. |
format |
JOUR |
author |
Lelli, S.M. Mazzetti, M.B. San Martín de Viale, L.C. |
author_facet |
Lelli, S.M. Mazzetti, M.B. San Martín de Viale, L.C. |
author_sort |
Lelli, S.M. |
title |
Hepatic alteration of tryptophan metabolism in an acute porphyria model. Its relation with gluconeogenic blockage |
title_short |
Hepatic alteration of tryptophan metabolism in an acute porphyria model. Its relation with gluconeogenic blockage |
title_full |
Hepatic alteration of tryptophan metabolism in an acute porphyria model. Its relation with gluconeogenic blockage |
title_fullStr |
Hepatic alteration of tryptophan metabolism in an acute porphyria model. Its relation with gluconeogenic blockage |
title_full_unstemmed |
Hepatic alteration of tryptophan metabolism in an acute porphyria model. Its relation with gluconeogenic blockage |
title_sort |
hepatic alteration of tryptophan metabolism in an acute porphyria model. its relation with gluconeogenic blockage |
url |
http://hdl.handle.net/20.500.12110/paper_00062952_v75_n3_p704_Lelli |
work_keys_str_mv |
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