Reference: Slepak T, et al. (2005) Intracellular galactose-1-phosphate accumulation leads to environmental stress response in yeast model. Mol Genet Metab 86(3):360-71

Reference Help

Abstract


In humans, deficiency of galactose-1-phosphate uridyltransferase (GALT) can lead a metabolic disorder Classic Galactosemia. Although the biochemical abnormalities associated with this disease have been described in detail, few attempts have been made to characterize the pathogenic mechanisms of this disorder at the molecular level. Here we report the use of high-throughput DNA microarray to examine how galactose affects gene expression in isogenic yeast models that are deficient in either galactokinase (GALK) or GALT, two enzymes which are essential for normal galactose metabolism. We confirmed that the growth of our GALT-deficient, but not GALK-deficient yeast strain ceased 4 h after challenge with 0.2% galactose. Such inhibition was not associated with a reduction of ATP content and was reversible after removal of galactose from medium. We compared the gene expression profiles of the GALT-deficient and GALK-deficient cells in the presence/absence of galactose. We revealed that in the absence of galactose challenge, a subset of genes involved in RNA metabolism was expressed at a level 3-fold lower in the GALT-deficient cells. Upon galactose challenge, significantly more genes involved in various aspects of RNA metabolism and almost all ribosomal protein genes were downregulated in the GALT-deficient, but not GALK-deficient cells. Remarkably, genes involved in inositol biosynthesis and turnover were exclusively induced at high level in the galactose-intoxicated GALT-deficient cells. Our data thus suggested that RNA metabolism, ribosome biogenesis, and inositol metabolism were likely targets for galactose-1-phosphate, a toxic intermediate that is uniquely accumulated under GALT-deficiency.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Slepak T, Tang M, Addo F, Lai K
Primary Lit For
Additional Lit For
Review For

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene/Complex Qualifier Gene Ontology Term Aspect Annotation Extension Evidence Method Source Assigned On Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Disease Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Disease Ontology Term Qualifier Evidence Method Source Assigned On Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Direction Regulation Of Happens During Method Evidence

Post-translational Modifications


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Site Modification Modifier Reference

Interaction Annotations


Genetic Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Assay Annotation Action Modification Source Reference

Functional Complementation Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Species Gene ID Strain background Direction Details Source Reference