Disease relevance of m-xylene

• In the presence of m-xylene, the Pu promoter of the TOL plasmid of Pseudomonas putida is activated by the prokaryotic enhancer-binding protein XylR [1].
• Initial reactions in anaerobic oxidation of m-xylene by the denitrifying bacterium Azoarcus sp. strain T [2].
• Good induction of the enzymes by m-toluate and m-methylbenzyl alcohol but not by m-xylene was measured in P. putida, but little or no regulation was found in E. coli [3].
• Molecular and biochemical characterization of two meta-cleavage dioxygenases involved in biphenyl and m-xylene degradation by Beijerinckia sp. strain B1 [4].
• 1-NN treatment caused severe respiratory toxicity that was prevented by prior m-xylene exposure [5].

Psychiatry related information on m-xylene

• The effects of m-xylene on body sway, reaction time performance, and overnight sleep were measured [6].
• The effects of combined exposure to m-xylene and n-butyl alcohol on rotarod performance and motor activity in rats and respiratory rate in mice were investigated in the condition of an acute inhalation experiment [7].

High impact information on m-xylene

• The results of the above experiments provide evidence that xylR positively controls the transcription of xylS in the presence of m-xylene or m-methylbenzyl alcohol [8].
• The nucleotide sequence of the xylS promoter resembles that of the promoter of the xylCAB operon for the m-xylene-degrading pathway, which is also activated by xylR in the presence of m-xylene or m-methylbenzyl alcohol [8].
• This study provides genetic evidence that the upstream-activating sequences (UAS), which serve as the binding sites for the pWW0-encoded XylR protein (the m-xylene-responsive sigma(54)-dependent activator of Pu), isolate expression of the upper TOL genes from any adventitious transcriptional flow originating further upstream [9].
• A genetic approach has been followed to locate the specific segment within A domain of XylR that is directly responsible for its down-regulation in the absence of inducer, as compared to that involved in effector (m-xylene) binding [10].
• Examination of the resulting phenotypes allowed the assignment of the A domain region near the central activation domain, as the portion of the protein responsible for the specific repression of XylR activity in the absence of m-xylene [10].

Chemical compound and disease context of m-xylene

• The Xy1R protein positively controls expression from the Pseudomonas putida TOL plasmid sigma 54-dependent Pu and Ps promoters, in response to the presence of aromatic effectors such as m-xylene, m-methylbenzyl alcohol, and p-chlorobenzaldehyde in the culture medium [11].
• Pseudomonas putida (arvilla) mt-2 carries genes for the catabolism of toluene, m-xylene, and p-xylene on a transmissible plasmid, TOL [12].
• Pseudocumene (1,2,4-trimethylbenzene) and 3-ethyltoluene were found to serve as growth substrates for Pseudomonas putida (arvilla) mt-2, in addition to toluene, m-xylene, and p-xylene as previously described [13].
• Permeabilized cells of m-xylene-grown Azoarcus sp. strain T catalyzed the addition of m-xylene to fumarate to form (3-methylbenzyl)succinate [2].
• Glucose and other C sources exert an atypical form of catabolic repression on the sigma54-dependent promoter Pu, which drives transcription of an operon for m-xylene degradation encoded by the TOL plasmid pWW0 in Pseudomonas putida [14].

Biological context of m-xylene

• The gene also activates the transcription of the same operon in the presence of m-xylene or m-methylbenzyl alcohol, but for this activation another regulatory gene, xylR, is required [8].
• The G3(MP2) results predict that sequential methylation of benzene rings with fewer than four methyl groups will preferentially occur on the ring, resulting in the series toluene, 1,3-dimethylbenzene, 1,2,4-trimethylbenzene, and 1,2,4,5-tetramethylbenzene [15].
• Product distribution studies reveal that the natural isoform is highly specific for para hydroxylation of toluene (kcat approximately 2 s-1 with respect to an alphabetagamma promoter), o-xylene (kcat approximately 0.8 s-1), m-xylene (kcat approximately 0.6 s-1), and other aromatic hydrocarbons [16].
• This aspect was validated by comparing the simulations of a binary interaction-based PBPK model with experimental data on the inhalation kinetics of m-xylene, toluene, ethyl benzene, dichloromethane, and benzene in mixtures of varying composition and complexity [17].
• In contrast, the conversion of m-xylene to 2,4-dimethylphenol followed single enzyme Michaelis-Menten kinetics, was inhibited selectively by furafylline, and correlated significantly with known CYP1A2 catalyzed reactions. cDNA-expressed CYP1A2 converted m-xylene to 2,4-dimethylphenol, with an apparent Km similar to that of the microsomal reaction [18].

Anatomical context of m-xylene

• Toluene- or m-xylene-grown strain T cells were induced to the same extent for oxidation of both hydrocarbons [19].
• Partition coefficients were measured and used to estimate the m-xylene concentration in the fibroblasts [20].
• The metabolism of a third P450 substrate, cyclopentadienyl manganese tricarbonyl (CMT), was also analyzed. m-Xylene caused significant inhibition of CMT metabolism at all time points in both nasal and pulmonary microsomes but was without effect on hepatic microsomal metabolism of this compound [21].
• The effect of acute ethanol-mediated inhibition of m-xylene metabolism on central nervous system (CNS) depression in the human worker population was investigated using physiologically based pharmacokinetic (PBPK) models and probabilistic random (Monte Carlo) sampling [22].
• The median elimination half-time of m-xylene from subcutaneous fat was 58 h (range 25--128 h) [23].

Associations of m-xylene with other chemical compounds

• With the exception of 2,4-dimethylphenol formation from m-xylene, ring hydroxylation accounted for < 5% of total metabolite formation [18].
• Sequence analysis of the 16S rRNA gene revealed a close relationship between strain EbS7 and the previously described marine sulfate-reducing strains NaphS2 and mXyS1 (similarity values, 97.6 and 96.2%, respectively), which grow anaerobically with naphthalene and m-xylene, respectively [24].
• This bssA null mutant strain was unable to grow under denitrifying conditions on either toluene or m-xylene, while growth on benzoate was unaffected [25].
• A P. putida DOT-T1E derivative bearing plasmid pWW0-xylE::Km transforms m-xylene (logP(ow) = 3.2) into 3-methylcatechol (logP(ow) = 1.8) [26].
• While most of the stresses downregulated the m-xylene biodegradation-related genes, some uncouplers of the respiratory chain (azide) and small doses of arsenate appeared to stimulate their expression [27].

Gene context of m-xylene

• The apparent K(s) value for the oxidation of m-xylene in intact cells of the xylN mutant was fourfold higher than that of the wild-type strain, although the TOL catabolic enzyme activities in cell extracts from the two strains were almost identical [28].
• Transcription from the promoter of a positive regulatory gene, xylS, on the TOL plasmid of Pseudomonas putida is activated by another positive regulator, XylR, in the presence of m-xylene and is dependent on RNA polymerase containing the NtrA protein (sigma 54) [29].
• The regulator was activated by m-toluate or benzoate, but not by m-xylene or m-methylbenzyl alcohol. the map positions of xylG and xylF were also determined [30].
• The xylE product, catechol 2,3-dioxygenase, was induced by m-xylene or m-methylbenzyl alcohol in the cells containing the fused operon when a 2.8-kilobase segment of the TOL plasmid was provided in trans [31].
• The regulatory gene xylR of the TOL plasmid, which functions positively on both xylABC and xylDEGF operons in the presence of m-xylene or m-methylbenzyl alcohol, was cloned onto an Escherichia coli vector, pACYC177 [31].

Analytical, diagnostic and therapeutic context of m-xylene

• The chosen level corresponds to the occupational exposure limit (8-h time weighted average) in Sweden. m-Xylene was monitored up to 24 h after exposure in exhaled air, blood, saliva, and urine by headspace gas chromatography. m-Methylhippuric acid (a metabolite of m-xylene) was analyzed in urine by high-performance liquid chromatography [32].
• A physiologically-based pharmacokinetic model, containing a skin compartment, was derived and used to simulate experimentally determined exposure to m-xylene, using human volunteers exposed under controlled conditions [33].
• When m-xylene was administered intraperitoneally, the effect of enzyme induction was shown only at the large dose, a finding which suggests that intraperitoneal administration is more similar to inhalation exposure than oral administration [34].
• The rat hepatic cytochrome P450 induction pattern caused by administration of a high peroral dose of methyl ethyl ketone (MEK, 1.4 ml/kg once daily for 3 consecutive days) and m-xylene (1.0 ml/kg X 3) was studied by catalytic activity and immunoblotting techniques [35].
• The efficiency of solvent adsorption using Permea-Tec general solvent pads, used for the detection of chemical breakthrough of protective clothing, was determined for methanol, acetone, ethyl methyl ketone, trichloroethylene (TriCE), tetrachloroethylene (TetCE), toluene, m-xylene, and D-limonene [36].

References