Disturbed biopterin and folate metabolism in the Qdpr-deficient mouse
Autor: | Masayo Mori-Kojima, Sho Shimaguchi, Feng Xu, Shun Ichiro Honda, Sho Sanechika, Minoru Sakurai, Kazunao Kondo, Chiho Sumi-Ichinose, Junpei Yamashita, Yusuke Sudo, Tadaomi Furuta, Masahiro Sugimoto, Tomoyoshi Soga, Hiroshi Ichinose, Rieko Nakata |
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Jazyk: | angličtina |
Předmět: |
Genetically modified mouse
Folate Quinonoid dihydropteridine reductase Biophysics Dihydrofolate reductase Biopterin Mice Transgenic Phenylalanine Biochemistry Mice chemistry.chemical_compound Folic Acid Structural Biology Dihydrobiopterin Genetics medicine Animals Metabolomics Molecular Biology Tetrahydrobiopterin biology Chemistry Cell Biology Dihydropteridine Reductase Kinetics Tetrahydrofolate Dehydrogenase QDPR Methotrexate Oxidative stress biology.protein Oxidoreductases medicine.drug |
Zdroj: | FEBS Letters. (21):3924-3931 |
ISSN: | 0014-5793 |
DOI: | 10.1016/j.febslet.2014.09.004 |
Popis: | Quinonoid dihydropteridine reductase (QDPR) catalyzes the regeneration of tetrahydrobiopterin (BH4), a cofactor for monoamine synthesis, phenylalanine hydroxylation and nitric oxide production. Here, we produced and analyzed a transgenic Qdpr−/− mouse model. Unexpectedly, the BH4 contents in the Qdpr−/− mice were not decreased and even increased in some tissues, whereas those of the oxidized form dihydrobiopterin (BH2) were significantly increased. We demonstrated that unlike the wild-type mice, dihydrofolate reductase regenerated BH4 from BH2 in the mutants. Furthermore, we revealed wide alterations in folate-associated metabolism in the Qdpr−/− mice, which suggests an interconnection between folate and biopterin metabolism in the transgenic mouse model. |
Databáze: | OpenAIRE |
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