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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

The sphingolipid metabolism diagram. Network of the SL metabolism system. Diagram was generated in Matlab Simbiology software. The full model contains 69 reactions, 39 modeled species and 37 reaction catalyzing enzymes. Oval boxes denote reacting molecule species, diamond boxes denote enzymes, circles denote reactions (small circles – transport, bigger circle metabolic reaction). Solid lines connect reactants with reaction, short dash lines connecting diamonds to reactions denote enzymatic catalyzing influence. Long dash lines connecting ovals to reactions denote inhibition
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Fig1: The sphingolipid metabolism diagram. Network of the SL metabolism system. Diagram was generated in Matlab Simbiology software. The full model contains 69 reactions, 39 modeled species and 37 reaction catalyzing enzymes. Oval boxes denote reacting molecule species, diamond boxes denote enzymes, circles denote reactions (small circles – transport, bigger circle metabolic reaction). Solid lines connect reactants with reaction, short dash lines connecting diamonds to reactions denote enzymatic catalyzing influence. Long dash lines connecting ovals to reactions denote inhibition

Mentions: Our model captures all essential elements of the complex network of sphingolipid metabolism excluding de novo ceramide synthesis which has been described by Vasquez et al. [26]. It illustrates the general behavior of selected subspecies in unspecified human tissue in nine subcellular compartments. These compartments represent the following organelles or their parts: the outer and inner layer of the cell membrane, the cytoplasm, the endoplasmic reticulum, the cytoplasmatic and lumenal face of the Golgi apparatus, the nucleus, the mitochondrion and the lysosome. Our model includes 69 reactions of molecular transport and biochemical transformation (Fig. 1).Fig. 1


Computational modeling of sphingolipid metabolism.

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

The sphingolipid metabolism diagram. Network of the SL metabolism system. Diagram was generated in Matlab Simbiology software. The full model contains 69 reactions, 39 modeled species and 37 reaction catalyzing enzymes. Oval boxes denote reacting molecule species, diamond boxes denote enzymes, circles denote reactions (small circles – transport, bigger circle metabolic reaction). Solid lines connect reactants with reaction, short dash lines connecting diamonds to reactions denote enzymatic catalyzing influence. Long dash lines connecting ovals to reactions denote inhibition
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: The sphingolipid metabolism diagram. Network of the SL metabolism system. Diagram was generated in Matlab Simbiology software. The full model contains 69 reactions, 39 modeled species and 37 reaction catalyzing enzymes. Oval boxes denote reacting molecule species, diamond boxes denote enzymes, circles denote reactions (small circles – transport, bigger circle metabolic reaction). Solid lines connect reactants with reaction, short dash lines connecting diamonds to reactions denote enzymatic catalyzing influence. Long dash lines connecting ovals to reactions denote inhibition
Mentions: Our model captures all essential elements of the complex network of sphingolipid metabolism excluding de novo ceramide synthesis which has been described by Vasquez et al. [26]. It illustrates the general behavior of selected subspecies in unspecified human tissue in nine subcellular compartments. These compartments represent the following organelles or their parts: the outer and inner layer of the cell membrane, the cytoplasm, the endoplasmic reticulum, the cytoplasmatic and lumenal face of the Golgi apparatus, the nucleus, the mitochondrion and the lysosome. Our model includes 69 reactions of molecular transport and biochemical transformation (Fig. 1).Fig. 1

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