Computational modeling of sphingolipid metabolism
| Autor: | Weronika Wronowska, Karol Nienałtowski, Anna Gambin, Agata Charzyńska |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cell signaling
Systems biology Cell Computational biology Biology Models Biological Cell membrane Structural Biology Alzheimer Disease Modelling and Simulation medicine Homeostasis Humans Computer Simulation Phosphorylation Molecular Biology Sphingolipids Applied Mathematics Neurodegeneration Autophagy Sphingolipid metabolism Cell Membrane Reproducibility of Results Biological Transport Compartmentalization (psychology) Kinetic model medicine.disease Sphingolipid Computer Science Applications Cell biology Kinetics medicine.anatomical_structure Modeling and Simulation Biocatalysis lipids (amino acids peptides and proteins) Sensitivity analysis Research Article |
| Zdroj: | BMC Systems Biology |
| ISSN: | 1752-0509 |
| Popis: | Background As suggested by the origin of the word, sphingolipids are mysterious molecules with various roles in antagonistic cellular processes such as autophagy, apoptosis, proliferation and differentiation. Moreover, sphingolipids have recently been recognized as important messengers in cellular signaling pathways. Notably, sphingolipid metabolism disorders have been observed in various pathological conditions such as cancer and neurodegeneration. Results The existing formal models of sphingolipid metabolism focus mainly on de novo ceramide synthesis or are limited to biochemical transformations of particular subspecies. Here, we propose the first comprehensive computational model of sphingolipid metabolism in human tissue. Contrary to the previous approaches, we use a model that reflects cell compartmentalization thereby highlighting the differences among individual organelles. Conclusions The model that we present here was validated using recently proposed methods of model analysis, allowing to detect the most sensitive and experimentally non-identifiable parameters and determine the main sources of model variance. Moreover, we demonstrate the usefulness of our model in the study of molecular processes underlying Alzheimer’s disease, which are associated with sphingolipid metabolism. Electronic supplementary material The online version of this article (doi:10.1186/s12918-015-0176-9) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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