title: Disturbed biopterin and folate metabolism in the Qdpr-deficient mouse.
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.
authors.affiliation: Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sudo
authors.affiliation: Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Sanechika
authors.affiliation: Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Yamashita
authors.affiliation: Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Shimaguchi
authors.affiliation: Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Honda
authors.affiliation: Department of Pharmacology, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
authors.forename: Chiho
authors.initials: C
authors.lastname: Sumi-Ichinose
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Mori-Kojima
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Nakata
authors.affiliation: Center for Biological Resources and Informatics, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Furuta
authors.affiliation: Center for Biological Resources and Informatics, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Sakurai
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
authors.affiliation: Department of Pharmacology, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
authors.forename: Kazunao
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan. Electronic address: hichinos@bio.titech.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichinose
mesh_terms: D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D005492:Folic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D007700:Kinetics; D055432:Metabolomics; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D010088:Oxidoreductases / Q000172:deficiency* / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism
chemical_list: D001708:Biopterins; C010920:dihydrofolate; D005492:Folic Acid; D010088:Oxidoreductases; C022513:quinonoid dihydropterin reductase; D013762:Tetrahydrofolate Dehydrogenase; C003402:sapropterin; D008727:Methotrexate
keywords: Dihydrofolate reductase; Folate; Oxidative stress; Quinonoid dihydropteridine reductase; Tetrahydrobiopterin