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Computational modeling of sphingolipid metabolism.

Wronowska W, Charzyńska A, Nienałtowski K, Gambin A - BMC Syst Biol (2015)

Bottom Line: Contrary to the previous approaches, we use a model that reflects cell compartmentalization thereby highlighting the differences among individual organelles.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Computer Science Polish Academy of Sciences, Warsaw, Poland. wwro@biol.uw.edu.pl.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Time evolution of molar concentrations of the following species (the dashed lines correspond to the homeostasis scenario and solid lines to the AD scenario): (a) ceramide species; (b) sphingosine species; (c) sphingosine-1-phosphate species; (d) species functionally related to AD
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Fig5: Time evolution of molar concentrations of the following species (the dashed lines correspond to the homeostasis scenario and solid lines to the AD scenario): (a) ceramide species; (b) sphingosine species; (c) sphingosine-1-phosphate species; (d) species functionally related to AD

Mentions: As far as the concentration of Sph species in the model output is concerned, an immediate decline was observed due to CDase down-regulation. This was followed by the accumulation of Sph species in all compartments due to increased concentrations of CER species, the substrates for Sph synthesis. We also observed decreased concentrations of S1P species in the AD scenario (Fig. 5).Fig. 5


Computational modeling of sphingolipid metabolism.

Wronowska W, Charzyńska A, Nienałtowski K, Gambin A - BMC Syst Biol (2015)

Time evolution of molar concentrations of the following species (the dashed lines correspond to the homeostasis scenario and solid lines to the AD scenario): (a) ceramide species; (b) sphingosine species; (c) sphingosine-1-phosphate species; (d) species functionally related to AD
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4537549&req=5

Fig5: Time evolution of molar concentrations of the following species (the dashed lines correspond to the homeostasis scenario and solid lines to the AD scenario): (a) ceramide species; (b) sphingosine species; (c) sphingosine-1-phosphate species; (d) species functionally related to AD
Mentions: As far as the concentration of Sph species in the model output is concerned, an immediate decline was observed due to CDase down-regulation. This was followed by the accumulation of Sph species in all compartments due to increased concentrations of CER species, the substrates for Sph synthesis. We also observed decreased concentrations of S1P species in the AD scenario (Fig. 5).Fig. 5

Bottom Line: Contrary to the previous approaches, we use a model that reflects cell compartmentalization thereby highlighting the differences among individual organelles.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Computer Science Polish Academy of Sciences, Warsaw, Poland. wwro@biol.uw.edu.pl.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus