Abstract
Tetrahydrobiopterin (BH4) metabolism is altered at various stages of life. BH4 deficiencies have been demonstrated in newborns (BH4-deficient Phenylketonuria-PKU) as well as in several neurological diseases including familial dystonia, Parkinson’s and Alzheimer’s disease, and normal aging (for review, see 1). BH4 was originally shown to be the essential cofactor for phenylalanine hydroxylase2. BH4 is perhaps best known as the essential cofactor for tyrosine and tryptophan hydroxylases, the initial and rate-limiting enzymes in dopamine and serotonin synthesis, respectively. BH4 administration in animals and cultured cells can enhance biogenic amine synthesis, and inhibition of BH4 synthesis lowers intracellular BH4 and reduces biogenic amine synthesis. Thus, BH4 therapy has been attempted in several of the diseases mentioned above with some success.
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Levine, R.A., States, J.C., Anastasiadis, P.Z., Kuhn, D.M. (1993). Cloning and Characterization of Genes Encoding Tetrahydrobiopterin Biosynthetic Enzymes. In: Ayling, J.E., Nair, M.G., Baugh, C.M. (eds) Chemistry and Biology of Pteridines and Folates. Advances in Experimental Medicine and Biology, vol 338. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2960-6_28
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DOI: https://doi.org/10.1007/978-1-4615-2960-6_28
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