Magnetic resonance imaging studies in patients with phenylketonuria (PKU) revealed white matter alterations that correlated to most recent blood phenylalanine (Phe) concentrations as well as to brain Phe concentrations measured by magnetic resonance spectroscopy. The clinical significance of these changes is unknown. Magnetic resonance imaging data thus have no impact on therapeutic recommendat...

OBJECTIVE The objective of this work was to determine whether cells overexpressing phenylalanine (Phe) hydroxylase (PAH) can significantly reduce Phe in vitro for potential use as a therapy for preventing maternal phenylketonuria. STUDY DESIGN Human 293T and WRL68 cell lines were transiently and stably transfected to overexpress PAH. Cells were encapsulated within microspheres of sodium algin...

The hydrolysis of the chromogenic peptide Pro-Thr-Glu-Phe-Phe(4-NO2)-Arg-Leu at the Phe-Phe(4-NO2) bond by nine aspartic proteinases of animal origin and seven enzymes from micro-organisms is described [Phe(4-NO2) is p-nitro-L-phenylalanine]. A further series of six peptides was synthesized in which the residue in the P3 position was systematically varied from hydrophobic to hydrophilic. The Ph...

Use of tetrahydrobiopterin for treatment of patients with phenylketonuria (PKU) is a ‘‘hot topic” among patients and doctors taking care of them. An increasing number of publications are describing decreases in blood phenylalanine (Phe) concentrations in persons receiving tetrahydrobiopterin. From the practical point of view, however, data on the extent of tetrahydrobiopterin responsiveness are...

This article summarizes the present knowledge, recent developments, and common pitfalls in the diagnosis, classification, and genetics of hyperphenylalaninemia, including tetrahydrobiopterin (BH4) deficiency. It is a product of the recent workshop organized by the European Phenylketonuria Group in March 2011 in Lisbon, Portugal. Results of the workshop demonstrate that following newborn screeni...

Phenylketonuria (PKU) is an autosomal recessive inborn disorder of the metabolism that occurs due to mutations in the gene that codifies enzyme called the phenylalanine hydroxylase (PAH) which is responsible for converting dietary phenylalanine (Phe) into tyrosine (Tyr) in the liver. This results in persistent elevated Phe blood and tissue concentrations, with potential toxic effects, particula...

Nitric oxide (NO) regulates numerous processes during endotoxemia and inflammation. However, the sequential changes in whole body (Wb) nitric oxide (NO) production during endotoxemia in vivo remain to be clarified. Male Swiss mice were injected intraperitoneally with saline (control group) or lipopolysaccharide (LPS group). After 0, 2, 4, 6, 9, 12, and 24 h, animals received a primed constant i...

Ribosomes from muscle of diabetic rats synthesized less polyphenylalanine than normal ribosomes at low magnesium concentrations (5 to 10 mM), but they were more active than normal ribosomes at high magnesium concentrations (12.5 to 20 mM). The magnesium dependence of binding of phenylalanyl transfer RNA to normal and diabetic ribosomes closely paralleled the synthesis of polyphenylalanine. A po...

The amino acid phenylalanine (Phe) is a critical metabolic node that plays an essential role in the interconnection between primary and secondary metabolism in plants. Phe is used as a protein building block but it is also as a precursor for numerous plant compounds that are crucial for plant reproduction, growth, development, and defense against different types of stresses. The metabolism of P...