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

doi:10.1016/j.febslet.2014.09.004

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 journal › Article › peer-review

38 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 language	English
Pages (from-to)	3924-3931
Number of pages	8
Journal	FEBS Letters
Volume	588
Issue number	21
DOIs	https://doi.org/10.1016/j.febslet.2014.09.004
Publication status	Published - 03-11-2014
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2014.09.004

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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.",

keywords = "Dihydrofolate reductase, Folate, Oxidative stress, Quinonoid dihydropteridine reductase, Tetrahydrobiopterin",

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

year = "2014",

month = nov,

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doi = "10.1016/j.febslet.2014.09.004",

language = "English",

volume = "588",

pages = "3924--3931",

journal = "FEBS Letters",

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T1 - Disturbed biopterin and folate metabolism in the Qdpr-deficient mouse

AU - Xu, Feng

AU - Sudo, Yusuke

AU - Sanechika, Sho

AU - Yamashita, Junpei

AU - Shimaguchi, Sho

AU - Honda, Shun Ichiro

AU - Sumi-Ichinose, Chiho

AU - Mori-Kojima, Masayo

AU - Nakata, Rieko

AU - Furuta, Tadaomi

AU - Sakurai, Minoru

AU - Sugimoto, Masahiro

AU - Soga, Tomoyoshi

AU - Kondo, Kazunao

AU - Ichinose, Hiroshi

PY - 2014/11/3

Y1 - 2014/11/3

N2 - 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.

AB - 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.

KW - Dihydrofolate reductase

KW - Folate

KW - Oxidative stress

KW - Quinonoid dihydropteridine reductase

KW - Tetrahydrobiopterin

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M3 - Article

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AN - SCOPUS:84908242249

SN - 0014-5793

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EP - 3931

JO - FEBS Letters

JF - FEBS Letters

IS - 21

ER -

Disturbed biopterin and folate metabolism in the Qdpr-deficient mouse

Abstract

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