title: Stimulation of hepatic phenylalanine hydroxylase activity but not Pah-mRNA expression upon oral loading of tetrahydrobiopterin in normal mice.
abstract: Tetrahydrobiopterin (BH4) supplementation in patients with BH4-responsive phenylalanine hydroxylase (PAH) deficiency is an alternative to low-phenylalanine diet. To further investigate hepatic BH4-responsiveness, oral administration of 50 mg BH4/kg/day for 5 weeks was performed in wild-type mice. We observed a 2-fold increase in PAH protein by quantitative Western blot analysis and a 1.7-fold increase in enzyme activity, but no change in Pah-mRNA expression by quantitative real-time PCR analysis in treated mice compared to controls. Our findings support the proposed chemical-chaperone effect of BH4 to protect PAH.
authors.affiliation: Division of Clinical Chemistry, Department of Pediatrics, University of Zürich, Switzerland.
authors.forename: Rossana
authors.initials: R
authors.lastname: Scavelli
authors.forename: Zhaobing
authors.initials: Z
authors.lastname: Ding
authors.forename: Nenad
authors.initials: N
authors.lastname: Blau
authors.forename: Jan
authors.initials: J
authors.lastname: Haavik
authors.forename: Aurora
authors.initials: A
authors.lastname: Martínez
authors.forename: Beat
authors.initials: B
authors.lastname: Thöny
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D010651:Phenylalanine Hydroxylase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D012333:RNA, Messenger; D001708:Biopterins; D010651:Phenylalanine Hydroxylase; C003402:sapropterin