Disease relevance of phenylalanine

• Kinetically, in mice infected at birth with LCMV ARM, as early as 3 weeks postinfection the Phe-to-Leu change was found in virus in the serum [1].
• Five specific amino acids in Escherichia coli dihydrofolate reductase and Photinus pyralis luciferase were replaced with d-phenylalanine and d-methionine, and the specific activities of the resulting enzymes were determined [2].
• A mecA-containing Staphylococcus aureus strain was grown in the presence of high concentrations of D-serine, D-threonine, and D-phenylalanine [3].
• Because of a possible late-onset phenylketonuria, Phe levels of untreated patients should be monitored carefully at least during the first year of life [4].
• Inconsistent results were obtained using D-phenylalanine and aprotinin (acute administration at the start of a migraine attack) [5].

Psychiatry related information on phenylalanine

• D-phenylalanine in endogenous depression [6].
• When PKU is moderately well controlled by a diet low in Phe (thus keeping the imbalance between Phe and Tyr in plasma within moderate limits) severe mental retardation is averted, but deficits remain in higher cognitive functions [7].
• Relatively small fluctuations in Phe concentration were found to influence neuropsychological task performance of PKU patients [8].
• The lack of differences in reaction time and P3 may be due to relatively good Phe control in children with PKU, or to the simplicity of the task [9].
• One of these compounds, D-phenylalanine (DPA), has been shown to increase the pain threshold in animals [10].

High impact information on phenylalanine

• In the total acid-soluble pool in brain concentrations of Phe were higher and other neutral amino acids lower in HMZ mice compared with either HTZ or BTBR mice indicating a partial saturation of the l-amino acid carrier at the blood brain barrier by the elevated plasma Phe concentrations [11].
• Alanine substitution or deletion of the carboxyl-terminal Phe570 in gp91phox resulted in a 2-fold reduction in superoxide production [12].
• 1-Aminocyclopropane-1-carboxylate (ACC) N-malonyltransferase from etiolated mung bean hypocotyls was examined for its relationship to D-phenylalanine N-malonyltransferase and other enzymes which transfer malonyl groups from malonyl-CoA to D-amino acids [13].
• Poly(A) RNA from D-phenylalanine-treated mycelium was therefore used to generate a cDNA library which was subsequently screened by hybrid-selected translation [14].
• The structures of the complexes of carboxypeptidase A with the amino acids D-phenylalanine and D-tyrosine are reported as determined by x-ray crystallographic methods to a resolution of 2.0 A [15].

Chemical compound and disease context of phenylalanine

• The D-phenylalanine-activating enzyme tyrocidine synthetase I (TycA) from Bacillus brevis ATCC 8185 was overexpressed in Escherichia coli, purified to homogeneity, and assayed for ATP-PPi exchange and covalent binding of phenylalanine by the thiotemplate mechanism [16].
• No differences in MKK4/SEK1 gene expression or in the 41 other metastasis and tumor suppressor genes were found in A375 melanoma cells cultured in Tyr- and Phe-deprived media [17].
• Tyrosine (Tyr) is an essential amino acid in phenylketonuria (PKU) because of the limited hydroxylation of phenylalanine (Phe) to Tyr [18].
• In addition, microinjections of compounds known to inhibit enkephalin degradation: D-phenylalanine (10 micrograms), puromycin (20 ng), Gly-Gly-Phe-Met (0.5 micrograms), and captopril (20 ng) induced a naloxone-reversible bradycardia [19].
• The findings were similar for fatal arrhythmias, although D-phenylalanine appeared to decrease the digoxin dose at the development of fatal arrhythmias [20].

Biological context of phenylalanine

• Ghrelin correlated negatively with Phe in all three groups, whereas it correlated positively with catecholamine levels and energy intake and negatively with BMI only in diet-controlled patients and controls [21].
• We coupled the Flexiresin system with a high-performance cell-free translation system and demonstrated protein mutagenesis with seven different Phe analogs in parallel [22].
• From these results, we conclude that phosphorylation of domain I residues plays a major role in in vivo transcription activity of the P protein, whereas in vivo replicative function of the protein does not require phosphorylation [23].
• Equilibrium dialysis experiments appeared to indicate that the dissociation constant of any binary enzyme/D-phenylalanine complex must be somewhat higher than the kinetics allowed (greater than 2 mM) [24].
• The results show that d-amino acids and certain Gly-l-Xaa dipeptides and tripeptides may act as acyl acceptors at the active site of the enzyme. d-Phenylalanine and Gly-l-Phe were the most effective d-amino acid and dipeptide acceptors, respectively [25].

Anatomical context of phenylalanine

• The absence of a correlation between ghrelin and catecholamines, energy intake, or BMI in PKU patients on an inadequate diet may be due to dysregulation of their neuroendocrine system and might be affected by high Phe levels in the stomach and/or central nervous system [21].
• Hydroxylated PBN and D-phenylalanine products were recovered from stool (microM/gm colonic contents/10(9) colony forming units) and urine (microM/h/ml), respectively, and quantified using electrochemical detection [26].
• By 5 weeks, viral nucleic acid obtained from peritoneal macrophages, spleen, lymph nodes, and liver showed the Phe-to-Leu change [1].
• A novel D-phenylalanine-derivative hypoglycemic agent A-4166 increases cytosolic free Ca2+ in rat pancreatic beta-cells by stimulating Ca2+ influx [27].
• The microdialysis probes were perfused with artificial cerebrospinal fluid containing 5 mM D-phenylalanine (flow rate 2 microL/min) [28].

Associations of phenylalanine with other chemical compounds

• The results indicated that urinary excretion (expressed per g of creatinine) of free and total PEA was significantly lower in the ADHD patients, and plasma levels of Phe and Tyr were also decreased in the ADHD subjects compared with the normal controls [29].
• H-1 MR spectroscopy was performed in eight patients to determine brain metabolite concentrations, including phenylalanine (PHE) concentration, and brain compartmentation [30].
• A reactivity order of Cys, Met >> Phe, Tyr, > Trp > Pro > His, Leu was determined under aerobic reaction conditions from MS/MS analysis of the radiolyzed peptide products [31].
• In addition to serum Phe levels, the assessment program consisted of comprehensive psychological testing, magnetic resonance imaging of the head, (1)H magnetic resonance spectroscopy, and genotyping [4].
• Using confluent monolayers of Caco-2 cells as a model of the intestinal epithelium, permeability coefficients were obtained from the steady-state flux of a series of neutral and zwitterionic peptides prepared from D-phenylalanine and glycine [32].

Gene context of phenylalanine

• Phenylalanine hydroxylase (PAH) deficiency results in accumulation of phenylalanine (Phe) in the brain and leads to pathophysiological abnormalities including cognitive defect, if Phe diet is not restricted [33].
• The N-terminal amino acid D-phenylalanine in astressin ¿cyclo(30-33) [D-Phe12, Nle21,38, Glu30, Lys33]h/rCRF-(12-41)¿, a potent CRF peptide antagonist, was replaced by a phenyldiazirine, the 4-(1-azi-2,2,2-trifluoroethyl)benzoyl (ATB) residue [34].
• Thyroid hormones, insulin-like growth factor I (IGF1), insulin-like growth factor binding protein (IGFBP3), selenium, zinc, and Phe blood levels were measured [35].
• CAT activity was significantly inhibited by Phe in vitro and in vivo, whereas GSH-Px activity was reduced in vivo but not in vitro and SOD activity was not altered by any treatment [36].
• Carbonic anhydrase activators. Activation of isoforms I, II, IV, VA, VII, and XIV with L- and D-phenylalanine and crystallographic analysis of their adducts with isozyme II: stereospecific recognition within the active site of an enzyme and its consequences for the drug design [37].

Analytical, diagnostic and therapeutic context of phenylalanine

• Eleven hyperactive boys were treated for 2 weeks with D-phenylalanine (20 mg/kg per day) and for 2 weeks with placebo in a double-blind crossover study [38].
• We evaluated morning preprandial plasma ghrelin levels in 14 diet-controlled and 15 poorly controlled PKU patients and 20 age- and body mass index (BMI)-matched healthy children (controls) and correlated its concentrations with those of Phe and catecholamines as well as with their BMI and 24-h nutrient intake [21].
• D-phenylalanine was not found to exhibit opiate receptor mediated analgesia in monkeys [39].
• Phe loading was performed in five patients with an oral dose of 100 mg/kg body wt L-Phe monitored by spectral EEG analysis [40].
• In a four-year longitudinal study we have found these deficits to be in the working memory and inhibitory control functions dependent upon dorsolateral prefrontal cortex in PKU children with plasma Phe levels 3-5 times normal [7].

References