Evaluation of metabolic changes in acute intermittent porphyria patients by targeted metabolomics

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• dc.contributor.author Gomez-Gomez, Àlex
• dc.contributor.author Aguilera, Paula
• dc.contributor.author Langohr, Klaus
• dc.contributor.author Casals, Gregori
• dc.contributor.author Pavon, Cristina
• dc.contributor.author Marcos del Águila, Josep, 1971-
• dc.contributor.author To-Figueras, Jordi
• dc.contributor.author Pozo Mendoza, Óscar J., 1975-
• dc.date.accessioned 2022-09-27T06:06:52Z
• dc.date.available 2022-09-27T06:06:52Z
• dc.date.issued 2022
• dc.description.abstract Acute intermittent porphyria (AIP) is an inherited rare hepatic disorder due to mutations within the hydroxymethylbilane gene. AIP patients with active disease overproduce aminolevulinic acid (ALA) and porphobilinogen (PBG) in the liver which are exported inducing severe neurological attacks. Different hepatic metabolic abnormalities have been described to be associated with this condition. The goal of this research was to explore the metabolome of symptomatic AIP patients by state-of-the art liquid chromatography-tandem mass spectrometry (LC-MS/MS). A case versus control study including 18 symptomatic AIP patients and 33 healthy controls was performed. Plasmatic levels of 51 metabolites and 16 ratios belonging to four metabolic pathways were determined. The results showed that the AIP patients presented significant changes in the two main areas of the metabolome under study: (a) the tryptophan/kynurenine pathway with an increase of tryptophan in plasma together with increase of the kynurenine/tryptophan ratio; and (b) changes in the tricarboxylic acid cycle (TCA) including increase of succinic acid and decrease of the fumaric acid/succinic acid ratio. We performed a complementary in vitro study adding ALA to hepatocytes media that showed some of the effects on the TCA cycle were parallel to those observed in vivo. Our study confirms in plasma previous results obtained in urine showing that AIP patients present a moderate increase of the kynurenine/tryptophan ratio possibly associated with inflammation. In addition, it also reports changes in the mitochondrial TCA cycle that, despite requiring further research, could be associated with an energy misbalance due to sustained overproduction of heme-precursors in the liver.
• dc.format.mimetype application/pdf
• dc.identifier.citation Gomez-Gomez A, Aguilera P, Langohr K, Casals G, Pavon C, Marcos J, To-Figueras J, Pozo OJ. Evaluation of metabolic changes in acute intermittent porphyria patients by targeted metabolomics. Int J Mol Sci. 2022 Mar 16;23(6):3219. DOI: 10.3390/ijms23063219
• dc.identifier.doi http://dx.doi.org/10.3390/ijms23063219
• dc.identifier.issn 1422-0067
• dc.identifier.uri http://hdl.handle.net/10230/54172
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof Int J Mol Sci. 2022 Mar 16;23(6):3219
• dc.rights © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword LC-MS/MS
• dc.subject.keyword Acute intermittent porphyria
• dc.subject.keyword Kynurenine
• dc.subject.keyword Metabolomics
• dc.subject.keyword Tricarboxylic acid cycle
• dc.subject.keyword Tryptophan
• dc.title Evaluation of metabolic changes in acute intermittent porphyria patients by targeted metabolomics
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion