Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MEK (2-butanone) when combined with MBK (2-hexanone) markedly enhanced MBK neurotoxicity. MBK in rat plasma after exposure to MBK/MEK increased with time. Metabolites of MBK identified in blood and urine of rats and guinea pigs were 2-hexanol and 2,5-hexanedione.
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PMID:Toxicity and metabolism of methyl n-butyl ketone. 17 51

To make clear how the n-hexane metabolism is modified by co-exposure with MEK, rats were exposed to various concentrations of MEK mixed with a fixed concentration of n-hexane. Twenty-four male Wistar rats were divided into four equal groups. Each group was exposed for 8 h to 2000 ppm n-hexane, 2000 ppm n-hexane plus 200 ppm MEK, 2000 ppm n-hexane plus 630 ppm MEK and 2000 ppm n-hexane plus 2000 ppm MEK, respectively. Free metabolites and the sum of free and conjugated metabolites of n-hexane were analyzed by gas chromatography. The main metabolite was 2-hexanol during the exposure and 2,5-hexanedione (2,5-HD) after the exposure in any group. The main metabolites, 2-hexanol and 2,5 HD, decreased in inverse proportion to the co-exposed MEK concentrations. The results suggest that augmentation of n-hexane neurotoxicity by MEK co-exposure could not be explained only by 2,5-HD. In addition, 2,5-HD is recommended as an index for biological monitoring of n-hexane exposure. However, one should be careful to evaluate the exposed n-hexane concentration by urinary 2,5-HD, because n-hexane metabolism could be largely modified by co-exposure with MEK.
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PMID:Changes in urinary n-hexane metabolites by co-exposure to various concentrations of methyl ethyl ketone and fixed n-hexane levels. 235 Feb 38

It is well known that n-hexane produces peripheral neuropathy, and 2,5-hexanedione, one of the metabolites of n-hexane, is thought to be the main causative agent. Recently, the metabolites of n-hexane in urine have been measured by gas chromatography, and 2,5-hexanedione was proved to be useful for the biological monitoring of n-hexane exposure. In the present experiment, we intended to clarify the change of n-hexane metabolites in the urine of rats exposed to various concentrations of n-hexane and to its mixture with toluene of MEK. In the first experiment, five separate groups of five rats each were exposed to 100, 500, 1000, or 3000 ppm of n-hexane, or fresh air respectively in an exposure chamber for 8 h a day. Urinary samples were gathered during exposure, 16, 24, and 40 h after exposure. Half of each sample was analyzed by gas chromatography after hydrolysis with acid and enzymes, and the other half was analyzed without hydrolysis. 2,5-Dimethylfuran, MBK, 2-hexanol, 2,5-hexanedione, and gamma-valerolactone could be identified as n-hexane metabolites in the urine. The main metabolites were 2-hexanol and 2,5-hexanedione. 2-Hexanol was mostly excreted during exposure, while most of the 2,5-hexanedione was excreted after the end of exposure. The amount of metabolites in the urine correlatively increased with the concentration of n-hexane from 100 to 1000 ppm, but the amount of metabolites scarcely increased when the concentration of n-hexane increased from 1000 to 3000 ppm.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes of n-hexane metabolites in urine of rats exposed to various concentrations of n-hexane and to its mixture with toluene or MEK. 665 98

Pseudomonas veronii MEK700 was isolated from a biotrickling filter cleaning 2-butanone-loaded waste air. The strain is able to grow on 2-butanone and 2-hexanol. The genes for degradation of short chain alkyl methyl ketones were identified by transposon mutagenesis using a newly designed transposon, mini-Tn5495, and cloned in Escherichia coli. DNA sequence analysis of a 15-kb fragment revealed three genes involved in methyl ketone degradation. The deduced amino acid sequence of the first gene, mekA, had high similarity to Baeyer-Villiger monooxygenases; the protein of the second gene, mekB, had similarity to homoserine acetyltransferases; the third gene, mekR, encoded a putative transcriptional activator of the AraC/XylS family. The three genes were located between two gene groups: one comprising a putative phosphoenolpyruvate synthase and glycogen synthase, and the other eight genes for the subunits of an ATPase. Inactivation of mekA and mekB by insertion of the mini-transposon abolished growth of P. veronii MEK700 on 2-butanone and 2-hexanol. The involvement of mekR in methyl ketone degradation was observed by heterologous expression of mekA and mekB in Pseudomonas putida. A fragment containing mekA and mekB on a plasmid was not sufficient to allow P. putida KT2440 to grow on 2-butanone. Not until all three genes were assembled in the recombinant P. putida was it able to use 2-butanone as carbon source. The Baeyer-Villiger monooxygenase activity of MekA was clearly demonstrated by incubating a mekB transposon insertion mutant of P. veronii with 2-butanone. Hereby, ethyl acetate was accumulated. To our knowledge, this is the first time that ethyl acetate by gas chromatographic analysis has been definitely demonstrated to be an intermediate of MEK degradation. The mekB-encoded protein was heterologously expressed in E. coli and purified by immobilized metal affinity chromatography. The protein exhibited high esterase activity towards short chain esters like ethyl acetate and 4-nitrophenyl acetate.
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PMID:Degradation of alkyl methyl ketones by Pseudomonas veronii MEK700. 1735 Oct 32