Disturbed biopterin and folate metabolism in the Qdpr-deficient mouse

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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<sup>-/-</sup> mouse model. Unexpectedly, the BH4 contents in the Qdpr<sup>-/-</sup> 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<sup>-/-</sup> mice, which suggests an interconnection between folate and biopterin metabolism in the transgenic mouse model.

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Xu, F., Sudo, Y., Sanechika, S., Yamashita, J., Shimaguchi, S., Honda, S. I., … Ichinose, H. (2014). Disturbed biopterin and folate metabolism in the Qdpr-deficient mouse. FEBS Letters, 588(21), 3924–3931. https://doi.org/10.1016/j.febslet.2014.09.004

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