{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:11:27Z","timestamp":1789827087561,"version":"4.0.1"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI14\/00147"],"award-info":[{"award-number":["PI14\/00147"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CPII16\/00027"],"award-info":[{"award-number":["CPII16\/00027"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Government of Catalonia","doi-asserted-by":"publisher","award":["2014SGR692"],"award-info":[{"award-number":["2014SGR692"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms23063219","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T22:09:58Z","timestamp":1647468598000},"page":"3219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Evaluation of Metabolic Changes in Acute Intermittent Porphyria Patients by Targeted Metabolomics"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8172-1827","authenticated-orcid":false,"given":"Alex","family":"Gomez-Gomez","sequence":"first","affiliation":[{"name":"Applied Metabolomics Research Group, IMIM, Hospital del Mar, Doctor Aiguader 88, 08003 Barcelona, Spain"},{"name":"Integrative Pharmacology and Systems Neuroscience Group, IMIM, Hospital del Mar, Doctor Aiguader 88, 08003 Barcelona, Spain"},{"name":"Department of Medicine and Life Sciences (CEXS-UPF), University Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Aguilera","sequence":"additional","affiliation":[{"name":"Diagnosis and Management of Porphyria Clinic, Department of Dermatologyt, Hospital Clinic, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7075-9192","authenticated-orcid":false,"given":"Klaus","family":"Langohr","sequence":"additional","affiliation":[{"name":"Integrative Pharmacology and Systems Neuroscience Group, IMIM, Hospital del Mar, Doctor Aiguader 88, 08003 Barcelona, Spain"},{"name":"Department of Statistics and Operations Research, Universitat Polit\u00e8cnica de Barcelona Barcelonatech, 08034 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3271-1371","authenticated-orcid":false,"given":"Gregori","family":"Casals","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Pavon","sequence":"additional","affiliation":[{"name":"Cerba Internacional, Pl. Ramon Llull 7-10, 08203 Sabadell, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Marcos","sequence":"additional","affiliation":[{"name":"Department of Medicine and Life Sciences (CEXS-UPF), University Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"To-Figueras","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1735-9728","authenticated-orcid":false,"given":"Oscar J.","family":"Pozo","sequence":"additional","affiliation":[{"name":"Applied Metabolomics Research Group, IMIM, Hospital del Mar, Doctor Aiguader 88, 08003 Barcelona, Spain"},{"name":"Integrative Pharmacology and Systems Neuroscience Group, IMIM, Hospital del Mar, Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/S0140-6736(09)61925-5","article-title":"Porphyrias","volume":"375","author":"Puy","year":"2010","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.ymgme.2019.03.002","article-title":"Pathogenesis and clinical features of the acute hepatic porphyrias (AHPs)","volume":"128","author":"Bonkovsky","year":"2019","journal-title":"Mol. 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