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

In this study, we reconstructed a fibroblast-specific genome-scale model based on the recently published, FAD-curated model, based on Recon3D reconstruction. To constrain the model we used transcriptomics, and proteomics data, which we obtained from healthy controls and Refsum disease patient fibroblasts incubated with phytol, a precursor of phytanic acid. Using this model, we investigated the metabolic phenotype of Refsum disease at the genome-scale, and we studied the effect of phytanic acid on cell metabolism. We identified 20 metabolites that were predicted to discriminate between Healthy and Refsum disease patients, several of which with a link to amino acid metabolism. Overall design: Comparison between control and Refsum disease patient cell lines (and models) metabolism, with or without exposure to phytol.