Possible Interaction: Phenylalanine and Tetrahydrobiopterin

“Results: Mean daily consumption of Phe increased significantly after the first year of BH4 treatment in group 2 compared to group 1 (p<0.05).”

“The rate of phosphorylation of human phenylalanine hydroxylase was inhibited about 40% by the cofactor tetrahydrobiopterin , and this inhibition was completely prevented by the simultaneous presence of L-phenylalanine (i.e. at turnover conditions).”

“Furthermore, the Km for phenylalanine in the presence of BH4 is 0.050 mM, a value that is one-fifth that of the recombinant rat liver enzyme.”

“Thus, phosphorylation of the enzyme by cAMP-dependent protein kinase is stimulated by phenylalanine , especially in the presence of BH4 , (which by itself inhibits), whereas phosphorylation sensitizes the enzyme to activation by phenylalanine.”

“Serum phenylalanine concentrations decreased in 4 patients with hyperphenylalaninemia after loading with tetrahydrobiopterin.”

“ Tetrahydrobiopterin (BH4; sapropterin) reduces phenylalanine (Phe) levels in responders, enabling relaxation of dietary therapy.”

“… 6R-tetrahydrobiopterin … phenylalanine intake (from 49.1 [25.6-60.3] to 56.5 [39.8-68.3] mgkg(-1)day(-1)) and natural protein intake (….8-1.7] to 1.5 [1.0-1.8] g kg(-1)day(-1)), and some patients managed to adopt normal diets.”

“BACKGROUND Sapropterin dihydrochloride BH4 , tetrahydrobiopterin) can lower plasma phenylalanine (Phe) concentrations for a subset of patients with phenylketonuria (PKU), an inborn error of metabolism.”

“On long-term BH4 treatment over a period of 48 ± 27 months in a dose of 14.9 ± 3.3mg/kg/day phenylalanine tolerance was increased from 452 ± 201 mg/day to 1593 ± 647 mg/day, corresponding to a mean increase of 1141 ± 528 mg/day.”

“Treatment with tetrahydrobiopterin (BH4), the natural cofactor of phenylalanine hydroxylase (PAH), can reduce blood phenylalanine (Phe) levels in patients with BH4-responsive phenylketonuria (PKU).”