The Relationship Between Biopterin and Folate Metabolism
Phenylketonuria (PKU) is a metabolic disorder that is inherited in an autosomal recessive pattern and is caused by a defect in the hepatic phenylalanine (PA) hydroxylating system. This system consists of two enzymes, phenylalanine 4-hydroxylase (PAH) (EC 188.8.131.52) and dihydropteridine reductase (DHPR) (EC 184.108.40.206), and a coenzyme, tetrahydrobiopterin (BH4), which acts not only on PAH but also on tyrosine 3-hydroxylase (EC 220.127.116.11) and tryptophan 5-hydroxylase (EC 18.104.22.168) — the former on the dopamine and norepinephrine synthesis pathway, the latter on the serotonin synthesis pathway (Fig. 1). During each hydroxylation cycle of these three enzymes, BH4 is oxidized to quininoid dihydrobiopterin (q-BH2), the latter being transformed partly into L-erythro-7, 8-dihydrobiopterin (7,8-BH2). They are reduced to BH4 by DHPR and by dihydrofolate reductase (DHFR) (EC 22.214.171.124), respectively (Fig. 1).
KeywordsBiogenic Amine Folate Metabolism Basal Ganglion Calcification Autosomal Recessive Pattern Dihydropteridine Reductase
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