ビオプテリンの生理機能と病態代謝

概要

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Tetrahydrobiopterin (BH4) is a cofactor for aromatic amino acid mono-oxygenases and nitric oxide synthases. Alteration in the content of tissue BH4 can affect a variety of physiological functions. GTP cyclohydrolase I is an enzyme for BH4-biosynthesis and the genetic defect in an allele of GTP cyclohydrolase I gene can cause hereditary dystonia, termed as DYT5, due to partial BH4 deficiency. Therefore, such a functional change associated with hereditary partial BH4 deficiency was analyzed using two types of partial biopterin-deficient transgenic mice, DPS-Pts^<-/-> mice and Spr-KO mice. Immunohistochemical analyses of DPS-Pts^<-/-> mice showed that tyrosine hydroxylase-immunoreactivity was weaker in the lateral region of the striatum than in the medial region or in the nucleus accumbens. It was also found that the motor coordination of limbs was disorganized in DPS-Pts^<-/-> mice, judging from the beam-walking test, whereas Spr-KO mice developed parkinsonian phenotypes like brady-kinesia and tremor. The brain levels of dopamine and tyrosine hydroxylase protein were markedly and concurrently increased from birth to early infantile in wild-type mice, whereas these increases were abolished in both types of partial biopterin-deficient mice. Our data suggest a close relevance of BH4 metabolism to brain development and the pathophysiology of neuropsychiatric disorders.
2014-03-25