{rfName}

Indexed in

License and use

Icono OpenAccess

Citations

23

Altmetrics

Grant support

]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).

Analysis of institutional authors

Aguilera PAuthorCasals GAuthorTo-Figueras JAuthor

Share

Publications
>
Article

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

Affiliations

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.

Keywords

acidacute intermittent porphyriakynureninelc-mslc-ms/msmetabolomicsmsplasmaserumtricarboxylic acid cycletryptophanurineAcute intermittent porphyriaAminolevulinic acidChromatography, liquidHumansKynurenineLc-ms/msMetabolomicsPerformance liquid-chromatographyPorphyria, acute intermittentSuccinic acidTandem mass spectrometryTricarboxylic acid cycleTrypto-phanTryptophan

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.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 1.61, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-31, the following number of citations:

  • WoS: 8
  • Scopus: 8
  • Europe PMC: 7
  • OpenCitations: 6

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 2025-05-31:

  • 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: 11.
  • 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: 11 (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: 1.25.
  • The number of mentions on the social network X (formerly Twitter): 2 (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.