Fibroblast-specific genome-scale modelling predicts an imbalance in amino acid metabolism in Refsum disease.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32160399", "kind": "science-record", "revision": 8, "content_hash": "sha256:91effb30c143056ba4fabf03d2e1119d387005e935ec77484f596f42aeaf30ac", "created_at": "2026-11-01T15:40:57Z", "updated_at": "2026-11-01T22:44:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Fibroblast-specific genome-scale modelling predicts an imbalance in amino acid metabolism in Refsum disease.", "doi": "10.1111/febs.15292", "pmid": "32160399", "authors": ["Agnieszka B Wegrzyn", "Katharina Herzog", "Albert Gerding", "Marcel Kwiatkowski", "Justina C Wolters", "Amalia M Dolga", "Alida E M van Lint", "Ronald J A Wanders", "Hans R Waterham", "Barbara M Bakker"], "journal": "The FEBS journal", "year": 2020, "abstract": "Refsum disease (RD) is an inborn error of metabolism that is characterised by a defect in peroxisomal α-oxidation of the branched-chain fatty acid phytanic acid. The disorder presents with late-onset 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-specific genome-scale model based on the recently published, FAD-curated model, based on Recon3D reconstruction. We used transcriptomics (available via GEO database with identifier GSE138379), metabolomics and proteomics (available via ProteomeXchange with identifier PXD015518) 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-specific 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. 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A subset of tasks relevant to fibroblast metabolism selected. For a full list of all tested tasks, see Table S5", "structure": {"pmcid": "PMC7754141", "section_index": 5, "section_title": "Model characterisation", "row_count": 13, "column_count": 3}, "table": {"label": "Table 1", "caption": "Model performance in the metabolic tasks test. A subset of tasks relevant to fibroblast metabolism selected. 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