Disease relevance of phenylalanine

• Of the 18 Fabs tested, 3, anti-S10, anti-S12, and anti-S14, inhibited polyphenylalanine synthesis; antibodies against 3 of the 21 E. coli ribosomal proteins (S1, S16, and S17) were not tested [1].
• Bacillus stearothermophilus 50 S ribosomal subunits active in polyphenylalanine (polyPhe) synthesis were reconstituted from a mixture of purified proteins and RNA [2].
• The activity of initiation factors obtained from free and membrane-bound polyribosomes of liver and of transplantable H5123 hepatoma of rats was investigated by using an assay of protein synthesis in vitro in which poly (U)-directed polyphenylalanine synthesis was measured [3].
• The synthesis of polyphenylalanine by Pseudomonas sp. strain Kim extracts was stimulated by putrescine and by S-(+)-2-hydroxyputrescine to a greater degree than was synthesis by E. coli extracts [4].
• Polyphenylalanine synthesis with ribosomes and two separated, partially purified elongation factors (EF) was measured in cell-free systems from the archaebacteria Thermoplasma acidophilum and Methanococcus vannielii, in an eukaryotic system from rat liver and an eubacterial one with Escherichia coli ribosomes and factors from Thermus thermophilus [5].

Psychiatry related information on phenylalanine

• Treatment of attention deficit disorder with DL-phenylalanine [6].

High impact information on phenylalanine

• This work shows that the phosphorylation of EF-2 by the EF-2 kinase results in a drastic inhibition of polyphenylalanine synthesis in poly(U)-directed translation [7].
• In vitro, the binding of labeled VM to ribosomes, followed by its detachment, yields particles unable to perform poly(U)-directed polyphenylalanine synthesis [8].
• The polyphenylalanine synthesis assay using the ribosomes constituted from the 60S subunit of AR100-9 and the 40S subunit of CHO indicated that the resistant phenotype of AR100-9 cells is due to an alteration of the 60S ribosomal subunit [9].
• ASF-shortened ribosomes showed normal subunit association but higher activity in poly(U)-dependent polyphenylalanine synthesis than the wild type (WT) ribosome at limited EF-G concentrations [10].
• The resultant hybrid ribosome was insensitive to thiostrepton and showed poly(U)-programmed polyphenylalanine synthesis dependent on the actions of both eukaryotic elongation factors 1alpha (eEF-1alpha) and 2 (eEF-2) but not of the prokaryotic equivalent factors EF-Tu and EF-G [11].

Chemical compound and disease context of phenylalanine

• The ribosomes functioned in polyuridylic acid-directed polyphenylalanine synthesis in the presence of S-100 from either C. burnetii or Escherichia coli [12].
• Four RIPs had similar activities on poly(U)-directed phenylalanine polymerization by E. coli ribosomes, and three RIPs inhibited poly(U)-directed polyphenylalanine synthesis by A. tumefaciens ribosomes, with submicromolar 50% inhibitory concentrations [13].
• Temperature-dependent inhibition of polyphenylalanine formation by the exotoxin of Bacillus thuringiensis [14].
• At 5 mM Mg2+, spermidine stimulation of polyphenylalanine synthesis by cell-free extracts of Escherichia coli was found to be about 30 times greater than that by extracts of Pseudomonas sp. strain Kim, a unique organism which lacks detectable levels of spermidine [4].
• We report on the long-term treatment of eight patients with mild and classical phenylketonuria (blood Phe levels maximum blood Phe levels between 771 and 1500 micromol/L) using BH4 at a dosage of 8-12 mg/kg BW per day [15].

Biological context of phenylalanine

• Fluorometric titration of tryptophans and correlation to eEF-2 residual activity on GTP hydrolysis and polyphenylalanine synthesis showed that modification of the two most reactive tryptophans completely inactivated the factor [16].
• Amino acid substitutions in protein biosynthesis. Poly(A)-directed polyphenylalanine synthesis [17].
• Phosphorylation of valyl-tRNA synthetase in response to PMA is reproducibly accompanied by a 1.7-fold increase in aminoacylation activity, whereas phosphorylation of EF-1 is associated with a 2.0-2.2-fold stimulation of activity, as measured by poly(U)-directed polyphenylalanine synthesis [18].
• Only substitutions of a neutral residue for aspartic acid and of a nonaromatic residue for phenylalanine (Phe) were associated with drug resistance [19].
• Over the range of concentrations which inhibited polyphenylalanine synthesis, binding was proportional to concentration, so that a unique binding site could not be detected [20].

Anatomical context of phenylalanine

• Wheat germ EF-1 alpha, EF-1 beta gamma, and EF-2 support polyphenylalanine synthesis on rabbit reticulocyte ribosomes as well as on yeast ribosomes [21].
• Poly (U, s 4-U) as a synthetic messenger RNA for polyphenylalanine synthesis in a cell-free system derivem derived from rat liver [22].
• These hybrid ribosomes are active in protein biosynthesis, as proven by polysome analysis and poly(U)-dependent polyphenylalanine synthesis [23].
• 15 mM Gln significantly inhibited net protein loss and protein breakdown compared to rates obtained in its absence (net protein loss, 200 +/- 230 vs 2080 +/- 200 nmol Phe/hindlimb per h; protein breakdown, 4566 +/- 480 vs 1614 +/- 180 nmol Phe/hindlimb per h; both p less than 0.01) [24].
• The rate of protein synthesis in HeLa cells was measured at various periods of time after addition of abrin and ricin to the medium and compared with the concurrent ability of the isolated ribosomes to support poly(U)-stimulated synthesis of polyphenylalanine in a cell-free system [25].

Associations of phenylalanine with other chemical compounds

• Both antibodies strongly inhibited polyuridylic acid-directed polyphenylalanine synthesis, ribosome-dependent GTPase activity, and the binding of elongation factor G to the ribosome at mole ratios over ribosomes of 4:1 or less [26].
• The sensitivity of IF-M1 activity to N-ethylmaleimide and heat (45 degrees) inactivation was tested in two model reactions requiring minimal complementary factors: (a) AUG-directed fMet-tRNAf binding to ribosomes; and (b) poly(U)-directed polyphenylalanine synthesis at 4 mM Mg2+ (IF-M2A, IF-M2B, EF-1, and EF-2 also required) [27].
• Proteins were omitted one at a time, and the resulting particles were examined by sucrose gradient sedimentation and assayed for polyPhe synthesis, peptidyltransferase activity, and in some cases binding of elongation factor EF-G and GTP, and association with a (20 S . Phe-tRNA . poly(U)) complex [2].
• Although thyroxine stimulates polyphenylalanine synthesis, it does not influence polyuridylic acid hydrolysis measured in the same reaction [28].
• In addition to valyl-tRNA synthetase activity, which was assigned to the 140-kDa component, the purified complex exhibits a potent Elongation Factor 1 activity, determined by its ability to sustain poly(U)-dependent polyphenylalanine synthesis in the presence of Elongation Factor 2 [29].

Gene context of phenylalanine

• A combination of 40 S subunits from yeast and "60 S" from wheat germ showed the stimulatory effect of EF-3 in polyphenylalanine synthesis (Chakraburtty, K., and Kamath, A. (1988) Int. J. Biochem. 20, 581-590) [30].
• Dephospho-EF-2 could support poly(U)-directed polyphenylalanine synthesis in a reconstituted elongation system when combined with EF-1 [31].
• The activity of EF-1 alpha is enhanced in polyphenylalanine synthesis by a complementary component, EF-1 beta delta [32].
• In heterozygous (+/cry1) diploids both the sensitive and the resistant genes are expressed as shown by studies of the action of cryptopleurine on polyphenylalanine-synthesizing systems derived from each parental sensitive and resistant haploid strain and heterozygous diploid strains [33].
• Genetic analysis of a mutation affecting the thermal response of the 50S ribosomal subunit to in vitro polyphenylalanine synthesis indicates that the gene, rit, is located near metB on the Escherichia coli chromosome and that the probable gene order is metB-rit-arg-rpo [34].

Analytical, diagnostic and therapeutic context of phenylalanine

• Fourteen mutant enzymes were purified to homogeneity, tested for feedback inhibition by Phe, and characterized by kinetic analysis and circular dichroism spectroscopy [35].
• Steady-state perfusion studies of rat jejunum indicated rapid carrier-assisted uptake of Phe and alpha-Asp-Phe, but only slow passive diffusion of beta-Asp-Phe and cyclo-Asp-Phe from the lumen [36].
• In a double-blind study, DL-phenylalanine (150--200 mg/24 h) or imipramine (150--200 mg/24 h) was administered to 40 depressed patients (20 patients in each group) for 30 days [37].
• FTIR and laser Raman spectra of beta-alanine beta-alaninium picrate and dl-phenylalanine dl-phenylalaninium picrate crystals of space group P1 (C(i)) have been me in the 4000-50cm(-1) range, at room temperature [38].
• DL-phenylalanine markedly potentiates opiate analgesia - an example of nutrient/pharmaceutical up-regulation of the endogenous analgesia system [39].

References