Disturbed biopterin and folate metabolism in the Qdpr-deficient mouse

Feng Xu, Yusuke Sudo, Sho Sanechika, Junpei Yamashita, Sho Shimaguchi, Shun Ichiro Honda, Chiho Sumi-Ichinose, Masayo Mori-Kojima, Rieko Nakata, Tadaomi Furuta, Minoru Sakurai, Masahiro Sugimoto, Tomoyoshi Soga, Kazunao Kondo, Hiroshi Ichinose

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3924-3931
Number of pages8
JournalFEBS Letters
Volume588
Issue number21
DOIs
Publication statusPublished - 2014 Nov 3

Keywords

  • Dihydrofolate reductase
  • Folate
  • Oxidative stress
  • Quinonoid dihydropteridine reductase
  • Tetrahydrobiopterin

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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