The regulatory roles of sphingolipids in diverse cell functions have been characterized extensively. However, the dynamics and interactions among the different sphingolipid species are difficult to assess, because de novo biosynthesis, metabolic inter-conversions, and the retrieval of sphingolipids from membranes form a complex, highly regulated pathway system. Here we analyze the heat stress response of this system in the yeast Saccharomyces cerevisiae and demonstrate how the cell dynamically adjusts its enzyme profile so that it is appropriate for operation under stress conditions before changes in gene expression become effective. The analysis uses metabolic time series data, a complex mathematical model, and a custom-tailored optimization strategy. The results demonstrate that all enzyme activities rapidly increase in an immediate response to the elevated temperature. After just a few minutes, different functional clusters of enzymes follow distinct activity patterns. Interestingly, starting after about six minutes, both de novo biosynthesis and all exit routes from central sphingolipid metabolism become blocked, and the remaining metabolic activity consists entirely of an internal redistribution among different sphingoid base and ceramide pools. After about 30 minutes, heat stress is still in effect and the enzyme activity profile is still significantly changed. Importantly, however, the metabolites have regained concentrations that are essentially the same as those under optimal conditions.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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Evidence ID | Analyze ID | File | Description |
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