Document Detail

A missense mutation of L-gulono-gamma-lactone oxidase causes the inability of scurvy-prone osteogenic disorder rats to synthesize L-ascorbic acid.
MedLine Citation:
PMID:  1400508     Owner:  NLM     Status:  MEDLINE    
The osteogenic disorder Shionogi (ODS) rat is a mutant Wistar rat that is subject to scurvy, because it lacks L-gulono-gamma-lactone oxidase, a key enzyme in L-ascorbic acid biosynthesis. Sequencing of polymerase chain reaction-amplified cDNAs for mutant and normal rat L-gulono-gamma-lactone oxidases demonstrated that the mutant cDNA has a single base mutation from G to A at nucleotide 182, which mutation alters the 61st amino acid residue from Cys to Tyr. To test the effect of this mutation on the expression of L-gulono-gamma-lactone oxidase, we inserted a region of the cDNAs coding for normal and mutant L-gulono-gamma-lactone oxidases into an expression vector, pSVL, and transfected COS-1 cells with such vectors. The result indicated that the defined amino acid substitution does decrease both the amount of immunologically detectable protein and the level of enzyme activity to about one-tenth of their normal values, while it does not affect the amount of the mRNA produced in the transfected cells. This situation is similar to our previous observation that L-gulono-gamma-lactone oxidase is expressed in the liver of the ODS rat at a very low level irrespective of the presence of a normal amount of L-gulono-gamma-lactone oxidase-specific mRNA of a normal size (Nishikimi, M., Koshizaka, T., Kondo, K., and Yagi, K. (1989) Experientia (Basel) 45, 126-129). Thus it became clear that the Cys-->Tyr substitution is responsible for the L-gulono-gamma-lactone oxidase deficiency in the ODS rat.
T Kawai; M Nishikimi; T Ozawa; K Yagi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  267     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1992 Oct 
Date Detail:
Created Date:  1992-11-25     Completed Date:  1992-11-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  21973-6     Citation Subset:  IM    
Institute of Applied Biochemistry, Yagi Memorial Park, Gifu, Japan.
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MeSH Terms
Ascorbic Acid / biosynthesis*
Base Sequence
Blotting, Northern
Cell Line, Transformed
Cells, Cultured
Genetic Predisposition to Disease
L-Gulonolactone Oxidase
Molecular Sequence Data
Polymerase Chain Reaction
RNA, Messenger / metabolism
Rats, Mutant Strains
Scurvy / genetics*
Sugar Alcohol Dehydrogenases / genetics*
Reg. No./Substance:
0/RNA, Messenger; 50-81-7/Ascorbic Acid; 9007-49-2/DNA; EC 1.1.-/Sugar Alcohol Dehydrogenases; EC Oxidase

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