Abstract
Can qualitative metabolite time course predictions be inferred from measured mRNA expression patterns? Speaking against this possibility is the large number of ‘decoupling’ control points that lie between these variables, i.e. translation, protein degradation, enzyme inhibition and enzyme activation. Speaking for it is the notion that these control points might be coordinately regulated such that action exerted on the mRNA level is informative of action exerted on the protein and metabolite levels. A simple kinetic model of sphingoid base metabolism in yeast is postulated. When the enzyme activities in this model are modulated proportional to mRNA expression levels measured in heat shocked yeast, the model yields a transient rise and fall in sphingoid bases followed by a permanent rise in ceramide. This finding is in qualitative agreement with experiments and is thus consistent with the aforementioned coordinated control system hypothesis.
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Selected References
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- Dickson R. C., Lester R. L. Yeast sphingolipids. Biochim Biophys Acta. 1999 Jan 6;1426(2):347–357. doi: 10.1016/s0304-4165(98)00135-4. [DOI] [PubMed] [Google Scholar]
- Dickson R. C., Nagiec E. E., Skrzypek M., Tillman P., Wells G. B., Lester R. L. Sphingolipids are potential heat stress signals in Saccharomyces. J Biol Chem. 1997 Nov 28;272(48):30196–30200. doi: 10.1074/jbc.272.48.30196. [DOI] [PubMed] [Google Scholar]
- Dickson R. C. Sphingolipid functions in Saccharomyces cerevisiae: comparison to mammals. Annu Rev Biochem. 1998;67:27–48. doi: 10.1146/annurev.biochem.67.1.27. [DOI] [PubMed] [Google Scholar]
- Eisen M. B., Spellman P. T., Brown P. O., Botstein D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863–14868. doi: 10.1073/pnas.95.25.14863. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hannun Y. A. Functions of ceramide in coordinating cellular responses to stress. Science. 1996 Dec 13;274(5294):1855–1859. doi: 10.1126/science.274.5294.1855. [DOI] [PubMed] [Google Scholar]
- Jenkins G. M., Richards A., Wahl T., Mao C., Obeid L., Hannun Y. Involvement of yeast sphingolipids in the heat stress response of Saccharomyces cerevisiae. J Biol Chem. 1997 Dec 19;272(51):32566–32572. doi: 10.1074/jbc.272.51.32566. [DOI] [PubMed] [Google Scholar]
- Nagiec M. M., Nagiec E. E., Baltisberger J. A., Wells G. B., Lester R. L., Dickson R. C. Sphingolipid synthesis as a target for antifungal drugs. Complementation of the inositol phosphorylceramide synthase defect in a mutant strain of Saccharomyces cerevisiae by the AUR1 gene. J Biol Chem. 1997 Apr 11;272(15):9809–9817. doi: 10.1074/jbc.272.15.9809. [DOI] [PubMed] [Google Scholar]
- Nagiec M. M., Skrzypek M., Nagiec E. E., Lester R. L., Dickson R. C. The LCB4 (YOR171c) and LCB5 (YLR260w) genes of Saccharomyces encode sphingoid long chain base kinases. J Biol Chem. 1998 Jul 31;273(31):19437–19442. doi: 10.1074/jbc.273.31.19437. [DOI] [PubMed] [Google Scholar]
- Schneiter R. Brave little yeast, please guide us to thebes: sphingolipid function in S. cerevisiae. Bioessays. 1999 Dec;21(12):1004–1010. doi: 10.1002/(SICI)1521-1878(199912)22:1<1004::AID-BIES4>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
- Skrzypek M. S., Nagiec M. M., Lester R. L., Dickson R. C. Analysis of phosphorylated sphingolipid long-chain bases reveals potential roles in heat stress and growth control in Saccharomyces. J Bacteriol. 1999 Feb;181(4):1134–1140. doi: 10.1128/jb.181.4.1134-1140.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]