INTRODUCTION Hyperphenylalaninemias are inborn errors of phenylalanine metabolism caused by deficiency of L-phenylalanine hydroxylase (the enzyme that converts phenylalanine to tyrosine), resulting in increased serum phenylalanine (>4 mg/dL or 240 µmol/L). Phenylketonuria, or PKU, is the most common form. Untreated PKU is associated with progressive neurodevelopmental delay, evolving towards in...

In normal individuals the major portion of ingested phenylalanine is converted into tyrosine. In the disease phenylpyruvic oligophrenia, however, ingested phenylalanine is converted mainly into phenylpyruvic and phenyllactic acids (l), which are excreted in the urine. This phenomenon has been ascribed to the inability of the body to convert phenylalanine to tyrosine (2) and a consequent shuntin...

Pancreatic protein and bicarbonate outputs were measured in dogs with pancreatic fistulas receiving intravenous secretin while individual L-amino acids or mixtures of L-amino acids were perfused into proximal intestine, Both phenylalanine and tryptophan were potent stimuli of pancreatic secretion; alanine, leucine, and valine increased protein outputs but their effects were small and not statis...

Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [(14)C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [(14)C]phenylalanine across the isolate...

Rats were given intraperitoneal injections of 2 mCi of carrier-free "Pi and substances known to activate liver phenylalanine hydroxylase. After 30 min, these animals were anesthetized and their livers removed for analysis of enzyme activity, 32Pi ncorporation into immunoprecipitated phenylalanine hydroxylase and [yS2P]ATP specific activity. Following glucagon treatment, rat liver phenylalanine ...

Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. The lack of activity at low levels of phenylalanine has been attributed to the N-terminus of the protein's regulatory domain acting as an inhibitory peptide by blocking substrate access to the active site. The location of the site at w...

The initial use of a tracer of phenylalanine was by Moss and Schoenheimer in rats in 1940 to determine that phenylalanine was hydroxylated to tyrosine, defining for the first time the primacy of this pathway. Phenylalanine and tyrosine kinetics were not measured in humans until the 1970-80s. The first application was to determine the degree of blockage of phenylalanine hydroxylation in patients...

The allosteric inhibition of M1-type pyruvate kinase from rabbit skeletal muscle by phenylalanine is reciprocally dependent on Mg2+ and phosphoenolpyruvate concentrations. At pH 8, phenylalanine acts as a competitive inhibitor with respect to Mg2+ and phosphoenolpyruvate, and vice versa. Phenylalanine introduces sigmoidicity into the dependence of the reaction velocity on [Mg2+]. In vitro kinet...