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
Jazyk: angličtina
Předmět:
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