scholarly journals Fibroblast‐specific genome‐scale modelling predicts an imbalance in amino acid metabolism in Refsum disease

FEBS Journal ◽  
2020 ◽  
Vol 287 (23) ◽  
pp. 5096-5113 ◽  
Author(s):  
Agnieszka B. Wegrzyn ◽  
Katharina Herzog ◽  
Albert Gerding ◽  
Marcel Kwiatkowski ◽  
Justina C. Wolters ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Refsum Disease ◽  
Scale Modelling ◽  
Genome Scale

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

2019 ◽  
Author(s):  
Agnieszka B. Wegrzyn ◽  
Katharina Herzog ◽  
Albert Gerding ◽  
Marcel Kwiatkowski ◽  
Justina C. Wolters ◽  
...  
Keyword(s):  
Amino Acid ◽  
Phytanic Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Disease Patient ◽  
Metabolic Phenotype ◽  
Scale Model ◽  
Refsum Disease ◽  
Model Based ◽  
Genome Scale

ABSTRACTRefsum disease 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 phytanic acid in plasma and tissues of patients. To date, no cure exists for Refsum disease, but phytanic acid 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 data (available via ProteomeXchange with identifier PXD015518), which we obtained from healthy controls and Refsum disease patient fibroblasts incubated with phytol, a precursor of phytanic acid.Our model correctly represents the metabolism of phytanic acid and displays fibroblast-specific metabolic functions. 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 53 metabolites that were predicted to discriminate between Healthy and Refsum disease patients, several of which with a link to amino acid metabolism. Ultimately, these insights in metabolic changes may provide leads for pathophysiology and therapy.

scholarly journals Toxicant-Induced Metabolic Alterations in Lipid and Amino Acid Pathways Are Predictive of Acute Liver Toxicity in Rats

2020 ◽  
Vol 21 (21) ◽  
pp. 8250
Author(s):  
Venkat R. Pannala ◽  
Shanea K. Estes ◽  
Mohsin Rahim ◽  
Irina Trenary ◽  
Tracy P. O’Brien ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Liver Toxicity ◽  
Exposure Dose ◽  
Plasma Metabolites ◽  
Sprague Dawley ◽  
Early Predictors ◽  
Genome Scale ◽  
Liver Response

Liver disease and disorders associated with aberrant hepatocyte metabolism can be initiated via drug and environmental toxicant exposures. In this study, we tested the hypothesis that gene and metabolic profiling can reveal commonalities in liver response to different toxicants and provide the capability to identify early signatures of acute liver toxicity. We used Sprague Dawley rats and three classical hepatotoxicants: acetaminophen (2 g/kg), bromobenzene (0.4 g/kg), and carbon tetrachloride (0.3 g/kg), to identify early perturbations in liver metabolism after a single acute exposure dose. We measured changes in liver genes and plasma metabolites at two time points (5 and 10 h) and used genome-scale metabolic models to identify commonalities in liver responses across the three toxicants. We found strong correlations for gene and metabolic profiles between the toxicants, indicative of similarities in the liver response to toxicity. We identified several injury-specific pathways in lipid and amino acid metabolism that changed similarly across the three toxicants. Our findings suggest that several plasma metabolites in lipid and amino acid metabolism are strongly associated with the progression of liver toxicity, and as such, could be targeted and clinically assessed for their potential as early predictors of acute liver toxicity.

Analysis of the cyanobacterial amino acid metabolism with a precise genome-scale metabolic reconstruction of Anabaena sp. UTEX 2576

2021 ◽  
pp. 108008
Author(s):  
Daniel A. Norena-Caro ◽  
Cristal Zuniga ◽  
Amber J. Pete ◽  
Sven A. Saemundsson ◽  
Morgan R. Donaldson ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Metabolic Reconstruction ◽  
Anabaena Sp ◽  
Genome Scale

Amino Acid Metabolism

1979 ◽  
Vol 7 (1) ◽  
pp. 261-262
Author(s):  
E. V. ROWSELL
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism

Effect of intravenous bicarbonate administration on postoperative amino acid metabolism

1985 ◽  
Vol 4 ◽  
pp. 141-146 ◽  
Author(s):  
K VESTERBERG ◽  
J BERGSTROM ◽  
P FURST ◽  
U LEANDER ◽  
E VINNARS
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism

Different sensitivity of glucose and amino acid metabolism to insulin in NIDDM

Diabetes ◽  
1993 ◽  
Vol 42 (12) ◽  
pp. 1868-1877 ◽  
Author(s):  
L. Luzi ◽  
A. S. Petrides ◽  
R. A. De Fronzo
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism
Sign in / Sign up

Export Citation Format

Share Document