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.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Slepak T,Tang M,Addo F,Lai Kdoi
10.1016/j.ymgme.2005.08.002subject
Has Abstractpub_date
2005-11-01 00:00:00pages
360-71issue
3eissn
1096-7192issn
1096-7206pii
S1096-7192(05)00251-9journal_volume
86pub_type
杂志文章abstract::The aim of this study was to evaluate the activity of daily living (ADL) and surgical interventions in patients with mucopolysaccharidosis IVA (MPS IVA). The factor(s) that affect ADL are age, clinical phenotypes, surgical interventions, therapeutic effect, and body mass index. The ADL questionnaire comprises three do...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2016.04.005
更新日期:2016-06-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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pub_type: 杂志文章,评审
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.06.015
更新日期:2012-11-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2006.08.011
更新日期:2007-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:2013-07-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.02.002
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/s1096-7192(03)00047-7
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/s1096-7192(02)00037-9
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2010.04.001
更新日期:2010-07-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.2001.3253
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2010.10.008
更新日期:2011-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.06.011
更新日期:2012-11-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2019.10.005
更新日期:2020-02-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2011.05.009
更新日期:2011-11-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.ymgme.2008.06.012
更新日期:2008-11-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2007.04.009
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2007.11.017
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2004.06.007
更新日期:2004-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2011.04.002
更新日期:2011-07-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.1998.2708
更新日期:1998-07-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.1998.2748
更新日期:1998-10-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 临床试验,杂志文章
doi:10.1016/j.ymgme.2014.02.007
更新日期:2014-05-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2008.04.004
更新日期:2008-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2004.01.010
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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更新日期:2020-08-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2008.12.014
更新日期:2009-04-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2014.05.004
更新日期:2014-07-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2013.05.020
更新日期:2013-09-01 00:00:00