Disturbed biopterin and folate metabolism in the Qdpr-deficient mouse

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. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.