TY - JOUR
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
N1 - Funding Information:
We would like to thank the members of our laboratory for their critical suggestions and discussions. This work was supported by KAKENHI from MEXT (Grant-in-Aid for Scientific Research (C) 21500305 to H.I. and 25460346 to C.S.-I.), CREST from JST , NEXT-Supported Program for the Strategic Research Foundation at Private Universities 2011–2015, and a Grant from Tsuruoka City and Yamagata Prefecture .
Publisher Copyright:
© 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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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U2 - 10.1016/j.febslet.2014.09.004
DO - 10.1016/j.febslet.2014.09.004
M3 - Article
C2 - 25240194
AN - SCOPUS:84908242249
SN - 0014-5793
VL - 588
SP - 3924
EP - 3931
JO - FEBS Letters
JF - FEBS Letters
IS - 21
ER -