{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T22:25:46Z","timestamp":1785363946614,"version":"3.55.0"},"reference-count":72,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Refsum disease (RD) is an inborn error of metabolism that is characterised by a defect in peroxisomal \u03b1\u2010oxidation of the branched\u2010chain fatty acid phytanic acid. The disorder presents with late\u2010onset progressive retinitis pigmentosa and polyneuropathy and can be diagnosed biochemically by elevated levels of phytanate in plasma and tissues of patients. To date, no cure exists for RD, but phytanate levels in patients can be reduced by plasmapheresis and a strict diet. In this study, we reconstructed a fibroblast\u2010specific genome\u2010scale model based on the recently published, FAD\u2010curated model, based on Recon3D reconstruction. We used transcriptomics (available via GEO database with identifier\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE138379\">GSE138379<\/jats:ext-link>\n                      ), metabolomics and proteomics (available via ProteomeXchange with identifier\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/pride\/archive\/projects\/PXD015518\">PXD015518<\/jats:ext-link>\n                      ) data, which we obtained from healthy controls and RD patient fibroblasts incubated with phytol, a precursor of phytanic acid. Our model correctly represents the metabolism of phytanate and displays fibroblast\u2010specific metabolic functions. Using this model, we investigated the metabolic phenotype of RD at the genome scale, and we studied the effect of phytanate on cell metabolism. We identified 53 metabolites that were predicted to discriminate between healthy and RD patients, several of which with a link to amino acid metabolism. Ultimately, these insights in metabolic changes may provide leads for pathophysiology and therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Databases<\/jats:title>\n                    <jats:p>\n                      Transcriptomics data are available via GEO database with identifier\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE138379\">GSE138379<\/jats:ext-link>\n                      , and proteomics data are available via ProteomeXchange with identifier\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/pride\/archive\/projects\/PXD015518\">PXD015518<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/febs.15292","type":"journal-article","created":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T13:06:03Z","timestamp":1583931963000},"page":"5096-5113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Fibroblast\u2010specific genome\u2010scale modelling predicts an imbalance in amino acid metabolism in Refsum disease"],"prefix":"10.1111","volume":"287","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4872-8626","authenticated-orcid":false,"given":"Agnieszka B.","family":"Wegrzyn","sequence":"first","affiliation":[{"name":"Systems Medicine of Metabolism and Signalling Laboratory of Paediatrics University of Groningen University Medical Centre Groningen The Netherlands"},{"name":"Analytical Biosciences and Metabolomics Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research Leiden University The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Herzog","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases Department of Clinical Chemistry Amsterdam UMC, Location AMC University of Amsterdam The Netherlands"},{"name":"Centre for Analysis and Synthesis Department of Chemistry Lund University Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Gerding","sequence":"additional","affiliation":[{"name":"Systems Medicine of Metabolism and Signalling Laboratory of Paediatrics University of Groningen University Medical Centre Groningen The Netherlands"},{"name":"Department of Laboratory Medicine University of Groningen University Medical Center Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Pharmacokinetics, Toxicology and Targeting Groningen Research Institute of Pharmacy (GRIP) University of Groningen The Netherlands"},{"name":"Mass Spectrometric Proteomics and Metabolomics Institute of Biochemistry University of Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justina C.","family":"Wolters","sequence":"additional","affiliation":[{"name":"Laboratory of Paediatrics University Medical Centre Groningen University of Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia M.","family":"Dolga","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology Groningen Research Institute of Pharmacy University of Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alida E. 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