Name
Title | ||
|---|---|---|
The effects of near optimal growth solutions in genome-scale human cancer metabolic model |
Abstract | ||
|---|---|---|
Cancer cells inefficiently produce energy through glycolysis even in ample oxygen, a phenomenon known as “aerobic glycolysis”. A characteristic of the rapid and incomplete catabolism of glucose is the secretion of lactate. Genome-scale metabolic models have been recently employed to describe the glycolytic phenotype of highly proliferating human cancer cells. Genome-scale models describe genotype-phenotype relations revealing the full extent of metabolic capabilities of genotypes under various environmental conditions. The importance of these approaches in understanding some aspects of cancer complexity, as well as in cancer diagnostics and individualized therapeutic schemes related to metabolism is evident. Based on previous metabolic models, we explore the metabolic capabilities and rerouting that occur in cancer metabolism when we apply a strategy that allows near optimal growth solution while maximizing lactate secretion. The simulations show that slight deviations around the optimal growth are sufficient for adequate lactate release and that glucose uptake and lactate secretion are correlated at high proliferation rates as it has been observed. Inhibition of lactate dehydrogenase-A, an enzyme involved in the conversion of pyruvate to lactate, substantially reduces lactate release. We also observe that activating specific reactions associated with the migration-related PLCγ enzyme, the proliferation rate decreases. Furthermore, we incorporate flux constraints related to differentially expressed genes in Glioblastoma Multiforme in an attempt to construct a Glioblastoma-specific metabolic model and investigate its metabolic capabilities across different glucose uptake bounds. |
Year | DOI | Venue |
|---|---|---|
2012 | 10.1109/BIBE.2012.6399774 | BIBE |
Keywords | DocType | Citations |
cancer complexity,lactate release,near optimal growth solution,previous metabolic model,lactate secretion,metabolic capability,genome-scale human cancer metabolic,Genome-scale metabolic model,lactate dehydrogenase-A,cancer cell,Glioblastoma-specific metabolic model,adequate lactate release | Conference | 0 |
PageRank | References | Authors |
0.34 | 0 | 3 |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Vangelis Sakkalis | 1 | 110 | 23.68 |
| Eleftheria Tzamali | 2 | 12 | 2.65 |
| Konstantinos Marias | 3 | 8 | 3.26 |