Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-Phenyllinoleamide (NPLA), the anilide of linoleic acid, has been regarded as a marker of the case oils associated with toxic oil syndrome, but the mechanisms of toxic injury remain enigmatic. Experimental data have related an increased systemic toxic effect of heated linoleic anilides to chemical structural modifications that might also be possible by in vivo metabolism; however, little is known about their metabolism. Taking into account that NPLA is a derivative of linoleic acid, a fatty acid that can be metabolized by lipoxygenase activity to a vast array of derivatives possessing biological activity, the objective has been to elucidate the oxidative metabolism of NPLA by mouse peritoneal macrophages, a cellular model with high lipoxygenase activity. Cells were incubated with 0.1 mM NPLA spiked with N-phenyl[1-14C]linoleamide. The metabolites were separated by high-performance liquid chromatography and individually collected prior to GC/MS analysis. Identification of trihydroxy-, monohydroxy- and epoxy-derivatives of NPLA, suggests that this xenobiotic can be metabolized via the same oxidative processes as for linoleic acid. Furthermore, identification of the non-amidated monohydroxylated and trihydroxylated derivatives of linoleic acid arising from NPLA suggests an amidase-like activity with release of aniline and the free fatty acid. These results provide information about possible biological structures arising from NPLA, and open the way to evaluate the biological significance of these metabolites in the inflammatory reactions associated with toxic oil syndrome.
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PMID:Mass spectrometric identification of N-phenyllinoleamide metabolites in mouse peritoneal macrophages. 765 69

1. N-phenyllinoleamide (NPLA), the anilide of linoleic acid, has been associated with the epidemiology of Toxic Oil Syndrome, but so far data available on its metabolism are scarce. On account of the similarities in chemical structure between linoleic acid and NPLA, the objective here has been to investigate the oxidative metabolism of this xenobiotic by human polymorphonuclear leukocytes. 2. Human polymorphonuclear leukocytes were incubated with 0.1 mM NPLA spiked with NPLA labelled either on the aniline or the fatty acid moieties. The metabolites were separated by high-performance liquid chromatography and individually collected prior to gas chromatography-mass spectrometry analysis. 3. Identification of the metabolites as N-phenyl-9-hydroxy- and N-phenyl-13-hydroxy-10,12-octadecenamide (9-HNPLA and 13-HNPLA) and their corresponding non-amidated metabolites, the 9-hydroxy- and 13-hydroxyoctadecenoic acids (9-HODE and 13-HODE), suggests that NPLA can be metabolized via the same hydroperoxidative processes acting upon linoleic acid. 4. Identification of free aniline as a NPLA metabolite suggests an amidase-like activity with liberation of aniline and the free fatty acid moieties.
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PMID:N-phenyllinoleamide metabolism by human polymorphonuclear leukocytes. 797 26

Mercapturates (S-substituted N-acetyl-L-cysteines) are terminal metabolites formed by the glutathione-dependent metabolism of electrophilic xenobiotics, including haloalkenes. Acylases catalyze the hydrolysis of N-acyl-L-amino acids, including many xenobiotic-derived mercapturates, to give fatty acids and amino acids as products. Although several acylases have been identified, the acylases that catalyze the deacetylation of the haloalkene-derived mercapturates have not been identified and characterized. Acylase I catalyzes the deacetylation of some haloalkene-derived mercapturates, including S-(1,1,2, 2-tetrafluoroethyl)-N-acetyl-L-cysteine, S-(2-chloro-1,1, 2-trifluoroethyl)-N-acetyl-L-cysteine, and S-(2-bromo-1,1, 2-trifluoroethyl)-N-acetyl-L-cysteine [Uttamsingh, V., et al. (1998) Chem. Res. Toxicol. 11, 800-809]. In the studies presented here, we identified a rat kidney acylase that catalyzed the hydrolysis of the haloalkene-derived mercapturates S-(1, 2-dichlorovinyl)-N-acetyl-L-cysteine, S-(1,2,3,4,4-pentachloro-1, 3-butadienyl)-N-acetyl-L-cysteine, and S-(2,2-dibromo-1, 1-difluoroethyl)-N-acetyl-L-cysteine. The substrate selectivity and amino acid sequence of the purified rat kidney acylase were studied. Although the sequence of the purified rat kidney acylase was somewhat identical with that of aspartoacylase, it did not catalyze the hydrolysis of N-acetyl-L-aspartate.
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PMID:Acylase-catalyzed deacetylation of haloalkene-derived mercapturates. 1052 69

Propanil (3,4-dichloropropionanilide) is a selective contact pesticide, recommended for post-emergence use in rice. This herbicide may end up in surface waters and present potential risk for aquatic vascular plants. Therefore, its toxicity was evaluated on Lemna minor L., an aquatic plant regularly used for toxicological studies, during time- and concentration-dependent exposure. Toxicity assessments were based on inhibition of growth of L. minor cultures after 24 days. The obtained results showed that the growth of Lemna was affected by the herbicide. The responses of the guaiacol peroxidase (G-POD) and glutathione S-transferase (GST) involved in the xenobiotic metabolism and antioxidative system were also investigated following Propanil exposure. Our results showed that Propanil has not induced enzymatic antioxidative defenses of L. minor. Both 3,4-dichloroaniline (3,4-DCA) and 3,4-dichloroacetanilide are the major metabolites in this plant. On the contrary, only 3,4-DCA was found in culture media after 4 days. Probably, the enzymatic hydrolysis by acyl acylamidase and the acetylation by acetyl-CoA are the major pathways for these transformation products, respectively. The results of this study showed that the selected aquatic plant has the potential to accumulate and metabolize rice herbicide, like Propanil. Based on these toxicity data this herbicide should impair the establishment of non-target aquatic plants.
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PMID:Growth rate effects, responses of antioxidant enzymes and metabolic fate of the herbicide Propanil in the aquatic plant Lemna minor. 1600 45

Comamonas sp. strain CNB-1 degrades nitrobenzene and chloronitrobenzene via the intermediates 2-aminomuconate and 2-amino-5-chloromuconate, respectively. Deamination of these two compounds results in the release of ammonia, which is used as a source of nitrogen for bacterial growth. In this study, a novel deaminase was purified from Comamonas strain CNB-1, and the gene (cnbZ) encoding this enzyme was cloned. The N-terminal sequence and peptide fingerprints of this deaminase were determined, and BLAST searches revealed no match with significant similarity to any functionally characterized proteins. The purified deaminase is a monomer (30 kDa), and its V(max) values for 2-aminomuconate and 2-amino-5-chloromuconate were 147 micromol x min(-1) x mg(-1) and 196 micromol x min(-1) x mg(-1), respectively. Its catalytic products from 2-aminomuconate and 2-amino-5-chloromuconate were 2-hydroxymuconate and 2-hydroxy-5-chloromuconate, respectively, which are different from those previously reported for the deaminases of Pseudomonas species. In the catalytic mechanism proposed, the alpha-carbon and nitrogen atoms (of both 2-aminomuconate and 2-amino-5-chloromuconate) were simultaneously attacked by a hydroxyl group and a proton, respectively. Homologs of cnbZ were identified in the genomes of Bradyrhizobium japonicum, Rhodopseudomonas palustris, and Roseiflexus sp. strain RS-1; these genes were previously annotated as encoding hypothetical proteins of unknown function. It is concluded that CnbZ represents a novel enzyme that deaminates xenobiotic compounds and/or alpha-amino acids.
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PMID:A novel deaminase involved in chloronitrobenzene and nitrobenzene degradation with Comamonas sp. strain CNB-1. 1725 10

The amphoteric surfactant N-oleoyl-N-methyltaurine, which is in use in skin-care products, was utilized by aerobic bacteria as the sole source of carbon or of nitrogen in enrichment cultures. One isolate, which was identified as Pseudomonas alcaligenes, grew with the xenobiotic compound as the sole source of carbon and energy. The sulfonate moiety, N-methyltaurine, was excreted quantitatively during growth, while the fatty acid was dissimilated. The initial degradative reaction was shown to be hydrolytic and inducible. This amidase reaction could be demonstrated with crude cell extracts. The excreted N-methyltaurine could be utilized by other bacteria in cocultures. Complete degradation of similar natural compounds in bacterial communities seems likely.
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PMID:Amphoteric surfactant N-oleoyl-N-methyltaurine utilized by Pseudomonas alcaligenes with excretion of N-methyltaurine. 1878 36

Erythropoietic Protoporphyria (EPP) is an inherited deficiency of ferrochelatase, the last enzyme of the heme pathway. Under general anaesthesia, some patients develop neurological dysfunction suggesting upregulation in heme biosynthesis similar to that described for acute porphyrias after xenobiotic administration. Our aim has been to evaluate whether Isoflurane induces alterations in the heme pathway in a mouse model for EPP. Administration of Isoflurane (a single dose of 2 ml/kg, i.p) to wild-type (+/+), heterozygous (+/Fechm1Pas) and homozygous (Fechm1Pas/Fechm1Pas) mice, was evaluated by measuring the activity of delta-aminolevulinic acid synthetase (ALA-S) and Porphobilinogen-deaminase (PBG-D) in different tissues, as well as Heme oxygenase (HO), cytochrome P-450, CYP2E1 and glutathione levels in liver. Porphyrin precursors were measured in 24 h-urine samples. Fechm1Pas/Fechm1Pas mice receiving anaesthesia show enhanced ALA-S and CYP2E1 activities in the liver and increased urinary excretion of porphyrin precursors. No alterations were found in either PBG-D or HO activities. Diminished glutathione levels suggest that anaesthesia may produce oxidative stress in these animals. In conclusion, Isoflurane induces ALA-S activity and increased excretion of porphyrin precursors in EPP mice. These findings appear to confirm our previous hypothesis and indicate that Isoflurane may be an unsafe anaesthetic not only for patients with acute porphyrias but also for individuals with non acute porphyrias.
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PMID:Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria. 1926

Phytoremediation--the use of plants to clean up polluted soil and water resources--has received much attention in the last few years. Although plants have the inherent ability to detoxify xenobiotics, they generally lack the catabolic pathway for the complete degradation of these compounds compared to microorganisms. There are also concerns over the potential for the introduction of contaminants into the food chain. The question of how to dispose of plants that accumulate xenobiotics is also a serious concern. Hence the feasibility of phytoremediation as an approach to remediate environmental contamination is still somewhat in question. For these reasons, researchers have endeavored to engineer plants with genes that can bestow superior degradation abilities. A direct method for enhancing the efficacy of phytoremediation is to overexpress in plants the genes involved in metabolism, uptake, or transport of specific pollutants. Furthermore, the expression of suitable genes in root system enhances the rhizodegradation of highly recalcitrant compounds like PAHs, PCBs etc. Hence, the idea to amplify plant biodegradation of xenobiotics by genetic manipulation was developed, following a strategy similar to that used to develop transgenic crops. Genes from human, microbes, plants, and animals are being used successfully for this venture. The introduction of these genes can be readily achieved for many plant species using Agrobacterium tumefaciens-mediated plant transformation or direct DNA methods of gene transfer. One of the promising developments in transgenic technology is the insertion of multiple genes (for phase 1 metabolism (cytochrome P450s) and phase 2 metabolism (GSH, GT etc.) for the complete degradation of the xenobiotics within the plant system. In addition to the use of transgenic plants overexpressed with P450 and GST genes, various transgenic plants expressing bacterial genes can be used for the enhanced degradation and remediation of herbicides, explosives, PCBs etc. Another approach to enhancing phytoremediation ability is the construction of plants that secrete chemical degrading enzymes into the rhizosphere. Recent studies revealed that accelerated ethylene production in response to stress induced by contaminants is known to inhibit root growth and is considered as major limitation in improving phytoremediation efficiency. However, this can be overcome by the selective expression of bacterial ACC deaminase (which regulates ethylene levels in plants) in plants together with multiple genes for the different phases of xenobiotic degradation. This review examines the recent developments in use of transgenic-plants for the enhanced metabolism, degradation and phytoremediation of organic xenobiotics and its future directions.
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PMID:Transgenic plants for enhanced biodegradation and phytoremediation of organic xenobiotics. 1937 78