Προβολή Εργασίας
In vivo ANALYSIS OF GALACTOSEMIA USING YEAST AS THE MODEL SYSTEM
Κ. Συριόπουλος1,2, Α. Παναγιώταρου1,3, Κ. Κατσικάνη1,4, Π. Πατιού1,4, B. Pesheva1,5, K. Lai6, Μ. Κλάπα1,7
1 ΙΤΕ/ΕΙΧΗΜΥΘ
2 Τμήμα Χημικών Μηχανικών, Πανεπιστήμιο Πατρών
3 Εθνικό Μετσόβιο Πολυτεχνείο
4 Τμήμα Βιολογίας, Πανεπιστήμιο Πατρών
5 Department of Biotechnology, University of Chemical Technology and Metallurgy, Sofia, Bulgaria
6 Department of Pediatrics, University of Miami School of Medicine, US
7 Department of Chemical and Biomolecular Engineering, University of Maryland, US |
ΣΥΝΤΟΜΗ ΠΕΡΙΛΗΨΗ
Classic galactosemia is the inborn error of galactose metabolism diagnosed by the deficiency of the second enzyme of the Leloir pathway, galactose-1-phosphate uridyltransferase (GAL7). At present, the molecular mechanisms leading to chronic physiological complications related to galactosemia remain unknown. Moreover, many regulatory phenomena related to galactose assimilation (GA) abnormalities cannot be explained by the current hypothesis about its function. In this context, further analyses of GA are required. Metabolic engineering and quantitative systems biology provide the most suited framework for these studies. Using yeast as the model system for GA analysis, two recombinant, GAL7-deficient (GAL7Δ) and GAL1-deficient (GAL1Δ) ? GAL1 being the first Leloir pathway gene-, strains of Saccharomyces cerevisiae were constructed. Metabolic output measurements of cell culture growth in shake-flask and fermentor experiments indicated that GAL7Δ has different phenotypic behavior than wild-type and GAL1Δ strains even in glucose-rich media. GAL1Δ was able to grow in galactose indicating, that ? at least in yeast ? alternative GA routes are potentially active. Both observations support the need for holistic studies to decipher GA function and defect mechanisms. Indeed, high-throughput transcriptomic analysis of Petri-dish experimental dataset allowed for the identification of biological interaction networks, enhancing the current resolution of GA and its interaction with the rest of the metabolism. These studies integrated with metabolomic studies are expected to further unravel currently unknown regulation mechanisms of GA and its defects.
Λέξεις Κλειδιά
galactose assimilation, Saccharomyces cerevisiae, analysis of metabolic regulation, metabolic engineering, systems biology, DNA microarrays, transcriptomics, metabolomics
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