Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We administered 6-fluoro-DL-tryptophan (6F-Trp) to rats (50-200 mg/kg i.p.) and evaluated its neurochemical effects on central catechole and indole compounds; we also determined the time course of its action, together with its metabolism and kinetics in four rat brain areas. Neither norepinephrine nor dopamine and its major metabolites were affected by 6F-Trp. With regard to serotonin (5-HT), 6F-Trp induced a transient depletion in all the brain areas studied, with a maximum of about 60-65% obtained between 1 and 3 hr depending on the dose administered. After 6 hr, 5-HT levels generally returned to control values. 5-Hydroxyindolacetic acid (5-HIAA) levels were also reduced 3 hr after administration (-40 to -60%). A large dose-dependent increase in tryptophan (Trp) was observed in the four brain areas, possibly because of an inhibition of Trp incorporation into protein, as suggested by experiments with mouse neuroblastoma cells. The brain elimination half-life of 6F-Trp was estimated at 0.5-1 hr. Regarding 6F-Trp metabolism, three new compounds were detected in all four brain areas after 6F-Trp administration. They were identified by means of liquid chromatography with electrochemical detection and/or radioenzymology, in comparison with fluorinated standards, or after NSD 1015 or pargyline coadministration with 6F-Trp. The first two 6F-Trp metabolites detected were probably 6-fluoro-5-hydroxytryptophan and 6-fluoro-5-HIAA. The third, identified and quantified by means of the two analytical methods, was 6-fluoro-5-HT (6F-5-HT). These findings suggest that 6F-Trp could be used as the in vivo precursor of 6F-5-HT with a view to tracing neuronal serotoninergic pools, as has already been done with platelets.
 ...
PMID:Metabolism of 6-fluoro-DL-tryptophan and its specific effects on the rat brain serotoninergic pathway. 768 71

Acrylamide quenching of the tryptophan fluorescence of the lambda-repressor at different protein concentrations indicates that one of the three tryptophan residues, W129, W142, and W230, undergoes a change in environment upon self-assembly, from dimer to associated species. Quenching data suggest that this tryptophan residue is inaccessible to low concentrations of acrylamide and is blue-shifted in the associated form. In the dimer, this tryptophan residue is highly accessible to acrylamide and is red-shifted. NBS oxidation, at protein concentrations which favor the associated form, showed that this tryptophan is also significantly protected from NBS oxidation. HPLC peptide mapping of NBS-oxidized lambda-repressor, amino acid analysis, and sequencing indicate that the protected, blue-shifted tryptophan is tryptophan 230. A mutant repressor (F235C) was specifically labeled at Cys 235 with an environment-sensitive probe, acrylodan. The acrylodan fluorescence of the labeled F235C lambda-repressor undergoes a significant blue-shift, accompanied by fluorescence enhancement, upon protein association. Along with other genetic evidence, these results suggest involvement of the C-terminal tail region in the self-assembly of the lambda-repressor.
 ...
PMID:Role of the C-terminal tail region in the self-assembly of lambda-repressor. 771 Oct 28

1. Tyrosine and tryptophan, as well as 26 metabolites of these amino acids, were analyzed simultaneously in urine specimens from patients with neuroblastoma and control infants by a three-dimensional HPLC system to develop an early diagnosis. 2. Levels of detected compounds in urine from patients with neuroblastoma were generally higher in the case of catecholamines and lower in the case of indolalkylamines than those in controls. 3. The pathways of Dopamine-3,4-Dihydroxyphenylacetic acid-Vanillylmandelic acid, Dopamine-3-Methoxy-4-hydroxyphenylethylene glycol-Vanillylmandelic acid and Tyrosine-4-Hydroxyphenylacetic acid-4 were, in particular, found to be active in patients with neuroblastoma.
 ...
PMID:Simultaneous analyses of monoamines and their metabolites in urine specimens of patients with neuroblastoma. 790 Sep 60

Accumulation of quinolinic acid and L-kynurenine occurs in the brain and/or blood following immune activation, and may derive from L-tryptophan following induction of indoleamine 2,3-dioxygenase and other kynurenine-pathway enzymes. In the present study a survey of various cell lines derived from either brain or systemic tissues showed that, while all cells examined responded to interferon-gamma by increased conversion of L-[13C6]tryptophan into L-kynurenine (human: B-lymphocytes, neuroblastoma, glioblastoma, lung, liver, kidney; rat brain: microglia, astrocytes and oligodendrocytes), only macrophage-derived cells (peripheral-blood mononuclear cells; THP-1, U-937) and certain liver cells (SKHep1) synthesized [13C6]quinolinic acid. Tumour necrosis factor-alpha enhanced the effects of interferon-gamma in THP-1 cells. Norharmane, 6-chloro-DL-tryptophan and 4-chloro-3-hydroxyanthranilate attenuated quinolinic acid formation by THP-1 cells with IC50 values of 51 microM, 58 microM and 0.11 microM respectively. Norharmane and 6-chloro-DL-tryptophan attenuated L-kynurenine formation with IC50 values of 43 microM and 51 microM respectively, whereas 4-chloro-3-hydroxyanthranilate had no effect on L-kynurenine accumulation. The reductions in L-kynurenine and quinolinic acid formation are consistent with the reports that norharmane is an inhibitor of indoleamine 2,3-dioxygenase, 6-chloro-DL-tryptophan is metabolized through the kynurenine pathway, and 4-chloro-3-hydroxyanthranilate is an inhibitor of 3-hydroxyanthranilate 3,4-dioxygenase. These results suggest that many tissues may contribute to the production of L-kynurenine following indoleamine 2,3-dioxygenase induction and immune activation. Quinolinic acid may be directly synthesized from L-tryptophan in both macrophages and certain types of liver cells, although uptake of quinolinic acid precursors from blood may contribute to quinolinic acid synthesis in cells that cannot convert L-kynurenine into quinolinic acid.
 ...
PMID:4-Chloro-3-hydroxyanthranilate, 6-chlorotryptophan and norharmane attenuate quinolinic acid formation by interferon-gamma-stimulated monocytes (THP-1 cells). 847 Oct 29

Rabbit muscle cytosolic creatine kinase (MM-CK) has been treated with N-bromosuccinimide, a reagent known to oxidize selectively the indole moiety of tryptophan residues of proteins in acidic conditions. Inactivation of the enzyme is achieved by modification of one residue per monomer. NBS treatment decreases the ultraviolet absorbance at 280 nm and the intrinsic fluorescence of the protein. From these data it can be deduced that the quantum yields of the four tryptophan residues of each monomer are different due to the more or less hydrophobic environment of each of them and that at least two of them are sufficiently close to Cys 282 to allow fluorescence energy transfer to an extrinsic fluorophore bound to this residue. The accessibility to iodide of the tryptophans has been evaluated during guanidinium chloride denaturation. These data allowed us to acquire a new insight into the environment, the contribution to intrinsic fluorescence and the role in enzymatic activity and fluorescence resonance energy transfer of the tryptophan residues of CK and to tentatively assign a position in the sequence to each of them.
 ...
PMID:Discrimination between the four tryptophan residues of MM-creatine kinase on the basis of the effect of N-bromosuccinimide on activity and spectral properties. 861 41

The homodimeric SecA protein is the peripheral subunit of the preprotein translocase in bacteria. It binds the preprotein and promotes its translocation across the bacterial cytoplasmic membrane by nucleotide modulated coinsertion and deinsertion into the membrane. SecA has two essential nucleotide binding sites (NBS; Mitchell & Oliver, 1993): The high-affinity NBS-I resides in the amino-terminal domain of the protein, and the low-affinity NBS-II is localized at 2/3 of the protein sequence. The nucleotide-bound states of soluble SecA were studied by site directed tryptophan fluorescence spectroscopy, tryptic digestion, differential scanning calorimetry, and dynamic light scattering. A nucleotide-induced conformational change of a carboxy-terminal domain of SecA was revealed by Trp fluorescence spectroscopy. The Trp fluorescence of a single Trp SecA mutant containing Trp775 decreased and increased upon the addition of NBS-I saturating concentrations of ADP or AMP-PNP, respectively. DSC measurements revealed that SecA unfolds as a two domain protein. Binding of ADP to NBS-I increased the interaction between the two domains whereas binding of AMP-PNP did not influence this interaction. When both NBS-I and NBS-II are bound by ADP, SecA seems to have a more compact globular conformation whereas binding of AMP-PNP seems to cause a more extended conformation. It is suggested that the compact ADP-bound conformation resembles the membrane deinserted state of SecA, while the more extended ATP-bound conformation may correspond to the membrane inserted form of SecA.
 ...
PMID:Domain interactions of the peripheral preprotein Translocase subunit SecA. 881 Sep 4

A xylanolytic amyloglucosidase of Termitomyces clypeatus was characterised with respect to other amyloglucosidases. The enzyme contained high alpha-helix destabilising amino acids but no sulphur amino acid. It contained high threonine and serine, analogous to other raw starch hydrolysing enzymes. Both xylanase and amyloglucosidase activities were gradually lost with the progress of tryptophan oxidation by NBS and total inactivation occurred after oxidation of 4-5 tryptophan residues. In the presence of substrates (either starch or xylan), complete inactivation of either activities was not noticed even after oxidation of 7.7 mol of tryptophan residues. Inactivation by HNBB was not possible in the absence of any denaturant. Only 4.9 mol of tryptophan could be modified in the presence of 5 M urea which resulted in only 42% inhibition of activity. Thus modified enzyme had higher Vm/Km and lower pH optima in comparison to those of native enzyme. It was suggested that tryptophan was present at the substrate binding site and not at the active site. No such change in activity was noticed after modification of tyrosine, lysine or arginine residues. HPGPLC analysis of both dilute and concentrated enzyme solution indicated that the enzyme existed as an equilibrium mixture of protomer-oligomer. Perhaps for this reason molar mass of NAI modified enzyme appeared to be almost half of that modified by NAI in presence of substrate. Arrhenius plot of the enzyme also indicated reversible oligomerisation as a function of temperature.
 ...
PMID:Characterisation of a xylanolytic amyloglucosidase of Termitomyces clypeatus. 918 49

In the end-stage renal disease patient, certain uremic compounds could influence the cellular accumulation of aluminum (Al). In this study, we examined the effect of 15 uremic ultrafiltrate fractions obtained by HPLC on the uptake and toxicity of Al in mouse hepatocytes (MH) in culture, a model system in which Al is taken up bound to transferrin (Tf). Uremic fractions 4 to 8, 12, 14, and 15 increased cellular Al uptake and aspartate aminotransferase release and decreased cell growth when Tf-Al, not Al citrate, was added to culture media. Compounds that have been extracted previously from these ultrafiltrate fractions (p-cresol, xanthine, tryptophan, hippuric acid, and o-hydroxyhippuric acid) were then tested for their effect on Al uptake and toxicity in MH at concentrations found in uremic serum. Significant Al uptake by MH was observed only when p-cresol was added together with Tf-Al. Time-response curves showed increased Al uptake and toxicity at p-cresol concentrations of 3 mg/dl in culture media. Dose-response curves confirmed that Al uptake and cell toxicity were proportional to p-cresol from 1.5 mg/dl to 3 mg/dl in culture media. p-Cresol was not toxic to MH in the absence of Tf-Al in media. p-Cresol increased Tf-associated Al uptake only because there was no effect on Al uptake when Al citrate was substituted, and studies with Tf-I125-Al in the presence of this compound showed increased Tf-I125 taken up by MH. p-Cresol did not increase Tf saturation with Al. p-Cresol also increased Tf-Al uptake in Friend erythroleukemia and neuroblastoma cells in culture. Our studies suggest that p-cresol and uremic fractions 4 to 8, 12, 14, and 15 increase the uptake and toxicity of Al in cultured MH. These compounds may play a role in the accumulation and toxicity of Al in the liver of end-stage renal disease patients and possibly in all cells that express Tf receptors.
 ...
PMID:P-Cresol, a uremic compound, enhances the uptake of aluminum in hepatocytes. 918 61

Carboxymethylcellulase (CMCase) was extracted and purified from an angiosperm parasite Cuscuta reflexa free from beta-glucosidase and other enzyme activities. The molecular mass and Stokes' radius of the purified enzyme are 144 kDa and 44 A, respectively. The diffusion coefficient and frictional ratio of the enzyme were 5.15 x 10(-7) cm2/sec and 1.27. The SDS-PAGE revealed homotetrameric nature of the enzyme with a subunit molecular mass of 35 +/- 1 kDa. Titration against DTNB and NBS revealed 19 sulfhydryl groups and 8 tryptophan groups, respectively, per mole of the enzyme. A sharp pH optimum at 5.0 was obtained. Cuscuta CMCase activity is unique amongst plant endoglucanases in being stimulated by Mg2+ and Mn2+ ions and by various thiols. Reaction product analysis, mode of enzyme action and substrate specificity test suggest the endo- nature of the purified CMCase. The enzyme showed K(m) value of 26 +/- 1 mg/ml for carboxymethylcellulose (sodium salt).
 ...
PMID:Physico-chemical and functional characterization of a high molecular weight carboxymethylcellulase from Cuscuta reflexa. 949 45

Microenvironment and conformation of the active site of xylanase from an extremophilic Bacillus was deciphered for the first time using fluorescence spectroscopy. NBS modified enzyme showed complete inactivation and the kinetic analysis implicated the presence of an essential tryptophan at the active site of xylanase. Xylan (0.5%) protected the enzyme completely from inactivation with NBS, whereas it afforded 35% protection against the loss of fluorescence, suggesting that not all the tryptophans are involved at the substrate binding site. Quenching studies revealed that acrylamide was more efficient than KI and CsCl as indicated by the higher Stern-Volmer quenching constants (Ksv). The steric factor represented by the percentage accessibility of the tryptophan residues of XylII was higher with the positively charged Cs+ (80) than with the negatively charged I- (10), suggesting that the tryptophan residues are located in a relatively electronegative environment. In the presence of 6 M Gdn HCl the fluorescence shifted to 350 nm with increased accessibility of the fluorophore to the quenchers. The proximity of the essential carboxyl groups with a high pKa value of 6.9 [Chauthaiwale and Rao (1994) Biochim. Biophys. Acta] probably contributes to the electronegative environment of the tryptophan residue. Our results on sequence analysis of the gene encoding for XylII (Accession Number U83602 in the GenBank database) have shown that Trp 61 is highly conserved and may play a role in the structure-function relationship of the enzyme.
 ...
PMID:Structural and functional role of tryptophan in xylanase from an extremophilic Bacillus: assessment of the active site. 970 58


<< Previous 1 2 3 4 5 6 7 Next >>