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

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. Differ...

ver descrição completa

Detalhes bibliográficos
Autores: Gómez Gómez, Àlex, Aguilera Peiró, Paula, Langohr, Klaus|||0000-0001-7075-9192, Casals Mercadal, Gregori, Pavón Solís, Cristina, Marcos del Aguila, Jose, To Figueras, Jordi, Pozo Mendoza, Oscar J.
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/371348
Acesso em linha:https://hdl.handle.net/2117/371348
https://dx.doi.org/10.3390/ijms23063219
Access Level:acceso abierto
Palavra-chave:Mathematical statistics
acute intermittent porphyria
metabolomics
LC-MS/MS
tricarboxylic acid cycle
tryptophan
kynurenine
Estadística matemàtica--Aplicacions
Classificació AMS::62 Statistics::62P Applications
Àrees temàtiques de la UPC::Matemàtiques i estadística::Estadística matemàtica
id ES_edd27dc08042f4fac02f2b056a7477ba
oai_identifier_str oai:upcommons.upc.edu:2117/371348
network_acronym_str ES
network_name_str España
repository_id_str
spelling Evaluation of metabolic changes in acute intermittent porphyria patients by targeted metabolomicsGómez Gómez, ÀlexAguilera Peiró, PaulaLangohr, Klaus|||0000-0001-7075-9192Casals Mercadal, GregoriPavón Solís, CristinaMarcos del Aguila, JoseTo Figueras, JordiPozo Mendoza, Oscar J.Mathematical statisticsacute intermittent porphyriametabolomicsLC-MS/MStricarboxylic acid cycletryptophankynurenineEstadística matemàtica--AplicacionsClassificació AMS::62 Statistics::62P ApplicationsÀrees temàtiques de la UPC::Matemàtiques i estadística::Estadística matemàticaAcute 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.This research was funded by Instituto de Salud Carlos III FEDER (grant number PI14/00147), Generalitat de Catalunya (research team grant number 2014SGR692) and Spanish Health National System (contract number CPII16/00027 for Oscar J Pozo).Peer Reviewed20222022-03-1620222022-07-27journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2117/371348https://dx.doi.org/10.3390/ijms23063219reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/3713482026-05-27T15:37:01Z
dc.title.none.fl_str_mv Evaluation of metabolic changes in acute intermittent porphyria patients by targeted metabolomics
title Evaluation of metabolic changes in acute intermittent porphyria patients by targeted metabolomics
spellingShingle Evaluation of metabolic changes in acute intermittent porphyria patients by targeted metabolomics
Gómez Gómez, Àlex
Mathematical statistics
acute intermittent porphyria
metabolomics
LC-MS/MS
tricarboxylic acid cycle
tryptophan
kynurenine
Estadística matemàtica--Aplicacions
Classificació AMS::62 Statistics::62P Applications
Àrees temàtiques de la UPC::Matemàtiques i estadística::Estadística matemàtica
title_short Evaluation of metabolic changes in acute intermittent porphyria patients by targeted metabolomics
title_full Evaluation of metabolic changes in acute intermittent porphyria patients by targeted metabolomics
title_fullStr Evaluation of metabolic changes in acute intermittent porphyria patients by targeted metabolomics
title_full_unstemmed Evaluation of metabolic changes in acute intermittent porphyria patients by targeted metabolomics
title_sort Evaluation of metabolic changes in acute intermittent porphyria patients by targeted metabolomics
dc.creator.none.fl_str_mv Gómez Gómez, Àlex
Aguilera Peiró, Paula
Langohr, Klaus|||0000-0001-7075-9192
Casals Mercadal, Gregori
Pavón Solís, Cristina
Marcos del Aguila, Jose
To Figueras, Jordi
Pozo Mendoza, Oscar J.
author Gómez Gómez, Àlex
author_facet Gómez Gómez, Àlex
Aguilera Peiró, Paula
Langohr, Klaus|||0000-0001-7075-9192
Casals Mercadal, Gregori
Pavón Solís, Cristina
Marcos del Aguila, Jose
To Figueras, Jordi
Pozo Mendoza, Oscar J.
author_role author
author2 Aguilera Peiró, Paula
Langohr, Klaus|||0000-0001-7075-9192
Casals Mercadal, Gregori
Pavón Solís, Cristina
Marcos del Aguila, Jose
To Figueras, Jordi
Pozo Mendoza, Oscar J.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mathematical statistics
acute intermittent porphyria
metabolomics
LC-MS/MS
tricarboxylic acid cycle
tryptophan
kynurenine
Estadística matemàtica--Aplicacions
Classificació AMS::62 Statistics::62P Applications
Àrees temàtiques de la UPC::Matemàtiques i estadística::Estadística matemàtica
topic Mathematical statistics
acute intermittent porphyria
metabolomics
LC-MS/MS
tricarboxylic acid cycle
tryptophan
kynurenine
Estadística matemàtica--Aplicacions
Classificació AMS::62 Statistics::62P Applications
Àrees temàtiques de la UPC::Matemàtiques i estadística::Estadística matemàtica
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-03-16
2022
2022-07-27
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2117/371348
https://dx.doi.org/10.3390/ijms23063219
url https://hdl.handle.net/2117/371348
https://dx.doi.org/10.3390/ijms23063219
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
instname_str Universitat Politècnica de Catalunya (UPC)
reponame_str UPCommons. Portal del coneixement obert de la UPC
collection UPCommons. Portal del coneixement obert de la UPC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869423563446943744
score 15,300719

Registos relacionados