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Impact on the Sustainable Development Goals (SDGs)

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Pavon, CristinaAuthor

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February 1, 2025
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Evaluation of Metabolic Changes in Acute Intermittent Porphyria Patients by Targeted Metabolomics

Publicated to: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 23 (6): 3219- - 2022-03-01 23(6), DOI: 10.3390/ijms23063219

Authors:

Gomez-Gomez, Alex; Aguilera, Paula; Langohr, Klaus; Casals, Gregori; Pavon, Cristina; Marcos, Josep; To-Figueras, Jordi; Pozo, Oscar J
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Affiliations

Cerba Int, Pl Ramon Llull 7-10, Sabadell 08203, Spain - Author
Hosp del Mar, IMIM, Appl Metabol Res Grp, Doctor Aiguader 88, Barcelona 08003, Spain - Author
Hosp del Mar, IMIM, Integrat Pharmacol & Syst Neurosci Grp, Doctor Aiguader 88, Barcelona 08003, Spain - Author
Univ Barcelona, Hosp Clin, Biochem & Mol Genet Unit, IDIBAPS, Villarroel 170, Barcelona 08036, Spain - Author
Univ Barcelona, Hosp Clin, Dept Dermatologyt, Diag & Management Porphyria Clin, Villarroel 170, Barcelona 08036, Spain - Author
Univ Politecn Barcelona Barcelonatech, Dept Stat & Operat Res, Barcelona 08034, Spain - Author
Univ Pompeu Fabra, Dept Med & Life Sci CEXS UPF, Doctor Aiguader 88, Barcelona 08003, Spain - Author
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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.
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Keywords

AcidAcute intermittent porphyriaGood health and well-beingKynureninKynurenineLc-msLc-ms/msMetabolomicsMsPerformance liquid-chromatographyPlasmaSeruTricarboxylic acid cycleTrypto-phanTryptophanUrine

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 66/285, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry & Molecular Biology.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-04-08:

  • WoS: 8
  • Scopus: 9
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-08:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 12.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 12 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/2117/371348
Continuing with the social impact of the work, it is important to emphasize that, due to its content, it can be assigned to the area of interest of ODS 3 - Ensure healthy lives and promote well-being for all at all ages, with a probability of 57% according to the mBERT algorithm developed by Aurora University.
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Project objectives

La aportación persigue los siguientes objetivos: analizar el metaboloma de pacientes sintomáticos con porfiria intermitente aguda (AIP) mediante espectrometría de masas LC-MS/MS; determinar los niveles plasmáticos de 51 metabolitos y 16 ratios en cuatro vías metabólicas; caracterizar las alteraciones en la vía triptófano/quinurenina y en el ciclo del ácido tricarboxílico (TCA) en pacientes con AIP; evaluar in vitro el efecto del ácido aminolevulínico (ALA) en hepatocitos para comparar con hallazgos in vivo; confirmar en plasma los cambios previamente observados en orina relacionados con la inflamación; y explorar posibles asociaciones entre las alteraciones metabólicas y el desbalance energético hepático derivado de la sobreproducción sostenida de precursores del hemo.
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Most relevant results

El estudio evaluó los cambios metabólicos en pacientes con porfiria intermitente aguda (AIP) mediante metabolómica dirigida. Los resultados más relevantes fueron: (1) aumento significativo de triptófano plasmático y del cociente quinurenina/triptófano en la vía del triptófano/quinurenina; (2) alteraciones en el ciclo del ácido tricarboxílico (TCA), con incremento de ácido succínico y disminución de la relación fumarato/ácido succínico; (3) confirmación en plasma de un aumento moderado del cociente quinurenina/triptófano previamente observado en orina, posiblemente vinculado a inflamación; y (4) evidencia in vitro que mostró efectos similares en el ciclo TCA tras la adición de ALA a cultivos de hepatocitos, sugiriendo un desbalance energético asociado a la sobreproducción hepática de precursores de hemo.
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Awards linked to the item

]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).
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