The pH optimum of rat liver phenylalanine hydroxylase is dependent on the structure of the cofactor employed and on the state of activation of the enzyme. The tetrahydrobiopterin-dependent activity of native phenylalanine hydroxylase has a pH optimum of about 8.5. In contrast, the 6,7-dimethyltetrahydropterin-dependent activity is highest at pH 7.0. Activation of phenylalanine hydroxylase eithe...

The enzymatic oxidation of phenylalanine to tyrosine has been studied as part of an investigation of the intermediates and enzyme systems involved in the biosynthesis of epinephrine. Womack and Rose (1) indicated that phenylalanine was converted to tyrosine in viva by showing that tyrosine is not essential when sufficient phenylalanine is available. Definite proof was provided by Moss and Schoe...

In isotopic experiments, the labeling pattern of glutamate opens a window on hepatic metabolism, particularly the citric acid cycle, gluconeogenesis and fatty acid oxidation. This is because glutamate is in isotopic equilibrium with a-ketoglutarate, whose labeling pattern is influenced by the following: 1) the contributions of glucose and fatty acids to acetyl-CoA, 2) the relative contributions...

Pyranose dehydrogenase (PDH), a member of the GMC family of flavoproteins, shows a very broad sugar substrate specificity but is limited to a narrow range of electron acceptors and reacts extremely slowly with dioxygen as acceptor. The use of substituted quinones or (organo)metals as electron acceptors is undesirable for many production processes, especially of food ingredients. To improve the ...

Kinetic analyses of the irreversible inhibition of L-tyrosine and L-phenylalanine transport in Bacillus subtilis by phenylalanine chloromethyl ketone revealed that the inhibition was due to an affinity labeling process. Phenylalanine chloromethyl ketone is a competetive inhibitor of L-tyrosine and L-phenylalanine transport. The K, values for irreversible inhibition of L-tyrosine and L-phenylala...

Dietary restriction of phenylalanine is the main treatment for phenylketonuria (PKU), and current estimates of requirements are based on plasma phenylalanine concentration and growth. The present study aimed to determine more precisely the phenylalanine requirements in patients with the disease by use of indicator amino acid oxidation, with L-[1-13C]lysine as the indicator. Breath 13CO2 product...

The derivation of a quantitative model of phenylalanine metabolism in humans is described. The model is based on the kinetic properties of pure recombinant human phenylalanine hydroxylase and on estimates of the in vivo rates of phenylalanine transamination and protein degradation. Calculated values for the steady-state concentration of blood phenylalanine, rate of clearance of phenylalanine fr...

We present a solvent-implicit minimalistic model potential among the amino acid residues of proteins, obtained by using the known native structures [deposited in the Protein Data Bank (PDB)]. In this model, the amino acid side chains are represented by a single ellipsoidal site, defined by the group of atoms about the center of mass of the side chain. These ellipsoidal sites interact with other...

To investigate intestinal and hepatic metabolism of phenylalanine, four conscious pigs (7.5 kg), bearing arterial, venous, and hepatic portal catheters, were fasted for 12 h and infused with [ phenyl-2H5]phenylalanine via a peripheral vein and [ carboxyl-13C]phenylalanine via the stomach. During the first 6 h of the infusion, the pigs remained fasted and received only the intravenous tracer. Du...