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Updated: Jun 14, 2026
A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
Published on: June 8, 2022
Drug target identification in sphingolipid metabolism by computational systems biology tools: metabolic control
F Betül Kavun Ozbayraktar1, Kutlu O Ulgen
1Department of Chemical Engineering, Bogazici University, 34342 Bebek, Istanbul, Turkey. betulkavun@gmail.com
Abstract:
Sphingolipids regulate cellular processes that are critically important in cell's fate and function in cancer development and progression. This fact underlies the basics of the novel cancer therapy approach. The pharmacological manipulation of the sphingolipid metabolism in cancer therapeutics necessitates the detailed understanding of the pathway. Two computational systems biology tools are used to identify potential drug target enzymes among sphingolipid pathway that can be further utilized in drug design studies for cancer therapy. The enzymes in sphingolipid pathway were ranked according to their roles in controlling the metabolic network by metabolic control analysis. The physiologically connected reactions, i.e. biologically significant and functional modules of network, were identified by metabolic pathway analysis. The final set of candidate drug target enzymes are selected such that their manipulation leads to ceramide accumulation and long chain base phosphates depletion. The mathematical tools' efficiency for drug target identification performed in this study is validated by clinically available drugs.
Insights
This study identifies novel cancer drug targets by analyzing the sphingolipid pathway. Computational tools pinpoint enzymes that, when manipulated, can lead to ceramide accumulation for cancer therapy.
Area of Science:
- Biochemistry
- Systems Biology
- Cancer Research
Background:
- Sphingolipids play a critical role in cell fate and function, significantly impacting cancer development and progression.
- Understanding the sphingolipid metabolic pathway is essential for developing novel cancer therapeutics that target these pathways.
- Pharmacological manipulation of sphingolipid metabolism offers a promising avenue for cancer treatment.
Purpose of the Study:
- To identify potential drug target enzymes within the sphingolipid pathway for cancer therapy using computational systems biology tools.
- To rank enzymes based on their control over the metabolic network and identify functionally significant pathway modules.
- To select candidate enzymes whose manipulation results in ceramide accumulation and long-chain base phosphates depletion.
Main Methods:
- Utilized two computational systems biology tools for analyzing the sphingolipid metabolic network.
- Applied metabolic control analysis to rank enzymes by their influence on the metabolic network.
- Employed metabolic pathway analysis to identify biologically significant and functionally connected reaction modules.
Main Results:
- Identified and ranked enzymes within the sphingolipid pathway based on their metabolic control.
- Determined physiologically connected reactions, representing functional modules of the network.
- Selected candidate drug target enzymes predicted to induce ceramide accumulation and deplete long-chain base phosphates.
Conclusions:
- Computational systems biology tools are effective for identifying drug targets in the sphingolipid pathway for cancer therapy.
- The identified candidate enzymes provide a basis for drug design studies aimed at cancer treatment.
- The study's approach was validated using clinically available drugs, confirming the efficiency of the mathematical tools.
