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Expression of human inositol monophosphatase suppresses galactose toxicity in Saccharomyces cerevisiae: possible implications in galactosemia

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Title Expression of human inositol monophosphatase suppresses galactose toxicity in Saccharomyces cerevisiae: possible implications in galactosemia
 
Creator MEHTA, DV
KABIR, A
BHAT, PJ
 
Subject galactose-1-phosphate uridyltransferase
myoinositol monophosphatase
gene
yeast
system
pyrophosphorylase
activation
deficiency
lithium
cloning
galactosemia
galactose toxicity
inositol monophosphatase
udp-glucose pyrophosphorylase
saccharomyces cerevisiae
 
Description A suppressor of galactose toxicity in a gal7 yeast strain (lacking galactose 1-phosphate uridyl transferase) has been isolated from a HeLa cell cDNA library. Analysis of the plasmid clone indicated that the insert has an ORF identical to that of hIMPase (human myo-inositol monophosphatase). The ability of hIMPase to suppress galactose toxicity is sensitive to the presence of Li+ in the medium. A gal7 yeast strain harboring a plasmid containing cloned hIMPase grows on galactose as a sole carbon source, hIMPase mediated galactose metabolism is dependent on the functionality of GAL1 as well as GAL10 encoded galactokinase and epimerase respectively. These results predicted that the UDP-glucose/galactose pyrophosphorylase mediated pathway may be responsible for the relief of galactose toxicity. Experiments conducted to test this prediction revealed that expression of UGP1 encoded UDP-glucose pyrophosphorylase can indeed overcome the relief of galactose toxicity. Moreover, expression of UGP1 allows a gal7 strain to grow on galactose as a sole carbon source. Unlike the hIMPase mediated relief of galactose toxicity, UGP1 mediated relief of galactose toxicity is lithium insensitive. Based on our results and on the basis of available information on galactose toxicity, we suggest an alternative explanation for the molecular mechanism of galactose toxicity. (C) 1999 .
 
Publisher ELSEVIER SCIENCE BV
 
Date 2011-07-25T01:46:59Z
2011-12-26T12:49:07Z
2011-12-27T05:34:51Z
2011-07-25T01:46:59Z
2011-12-26T12:49:07Z
2011-12-27T05:34:51Z
1999
 
Type Article
 
Identifier BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1454(3), 217-226
0925-4439
http://dx.doi.org/10.1016/S0925-4439(99)00037-X
http://dspace.library.iitb.ac.in/xmlui/handle/10054/6597
http://hdl.handle.net/10054/6597
 
Language en