Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036474 (scurvy)
 685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:A missense mutation of L-gulono-gamma-lactone oxidase causes the inability of scurvy-prone osteogenic disorder rats to synthesize L-ascorbic acid. 140 May 8

L-Gulono-gamma-lactone oxidase (GLO), an enzyme that is missing in scurvy-prone animals, was produced in COS-1 cells by transfection with a minigene constructed from pSVL vector and rat GLO cDNA. A functional GLO protein was expressed, which was indistinguishable from rat GLO in molecular size. The microsomes obtained from the transfected COS-1 cells showed GLO activity comparable to that in rat liver microsomes.
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PMID:Expression in monkey cells of the missing enzyme in L-ascorbic acid biosynthesis, L-gulono-gamma-lactone oxidase. 204 88