In vitro biotransformation of 2-methylpropene (isobutene): Epoxide formation in mice liver

Cornet, Miranda; Sonck, Walter; Callaerts, A.; Csanády, Georg; Vercruysse, Antoine; Laib, R. J.; Rogiers, Vera

doi:10.1007/bf01968959

Cited by 9 publications

(7 citation statements)

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“…The source of this compound is speculated to be terpenes or ubiquinones. Animal models have proven that it is metabolized by cytochrome P450 enzymes to epoxides [30,31]. Terpenes and terpenoids are the primary constituents of the essential oils of many plants.…”

Section: Discussionmentioning

confidence: 99%

Breath biomarkers of liver cirrhosis

Dadamio

Velde

Laleman

et al. 2012

Journal of Chromatography B

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The diagnosis of asymptomatic cirrhosis in patients with liver disease is of importance to start screening for complications in due time. Liver biopsy is neither sensitive nor practical enough to be used as a frequent follow-up test in patients with chronic liver disease. The volatile organic compounds present in exhaled breath offer the possibility of exploring internal physiologic and pathologic process in a non invasive way. This study examined whether a specific pattern of biomarkers can be found in breath samples of patients with cirrhosis. To this aim samples of alveolar breath from patients with cirrhosis and healthy volunteers were analyzed using gas chromatography-mass spectrometry. When linear discriminant analysis was used to search for a model(s)/pattern of compounds characteristic for liver cirrhosis, 24 models of 8 independent compounds could distinguish between the groups. The sensitivity and specificity (between 82% and 88%, and 96% and 100%, respectively) of the models suggest that a specific pattern of breath biomarkers can be found in patients with cirrhosis, which may allow detecting this complication of chronic liver disease in an early stage.

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Section: Discussionmentioning

confidence: 99%

Breath biomarkers of liver cirrhosis

Dadamio

Velde

Laleman

et al. 2012

Journal of Chromatography B

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“…The gas chromatographic conditions were as described previously (2). The total amount of MEP present in gas and liquid phase was calculated (2).…”

Section: Methodsmentioning

confidence: 99%

“…2-Methyl-l,2-epoxypropane (MEP) has been identified as the primary metabolite of MP in liver tissue of rodents. MP is converted, in vitro (2) as well as in vivo (3), to this reactive epoxide intermediate. It can subsequently be hydrolyzed to a diol or conjugated to glutathione to form more hydrophilic metabolites (2), as shown in Figure 1.…”

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confidence: 99%

“…MP is converted, in vitro (2) as well as in vivo (3), to this reactive epoxide intermediate. It can subsequently be hydrolyzed to a diol or conjugated to glutathione to form more hydrophilic metabolites (2), as shown in Figure 1. Due to their electrophilic reactivity, epoxides may react with nucleophilic centers in the cell, inducing alterations of critical cellular macromol- ecules, such as DNA, RNA, and proteins, which may disturb normal biochemical processes and may lead to cytotoxic and genotoxic effects (4).…”

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Species-Dependent Differences in Biotransformation Pathways of 2-Methylpropene (Isobutene)

Cornet

Callaerts

Jorritsma³

et al. 1995

Chem. Res. Toxicol.

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The biotransformation of 2-methylpropene, a gaseous alkene widely used in industry, was investigated in vitro in liver tissue of rats, mice, and humans. Interspecies comparison revealed that the lowest levels of the primary epoxide metabolite were detected in incubations of 2-methylpropene with human liver homogenate, followed by rat and mouse, respectively. Among the human liver samples, however, important interindividual variations were observed. Out of the 16 samples analyzed, only 2 contained measurable epoxide amounts, while in the other samples only traces were detectable. The involvement of rat liver cytochrome P450 2E1 in the activation of 2-methylpropene to its epoxide 2-methyl-1,2-epoxypropane has been established. The lower capacity of the mixed function oxidase system in human liver samples compared to rodents is confirmed. Concerning epoxide detoxifying enzymes, a high microsomal epoxide hydrolase activity was observed in human liver tissue and an intermediate in rat liver, while a low activity was measured in mouse liver. These findings were inversely correlated with the epoxide levels measured in vitro in liver tissue of the three species studied. It can be concluded that, as far as the in vitro metabolism of 2-methylpropene is concerned, neither mouse nor rat represents a good model for the human situation. Although, the same biotransformation pathways are involved, marked quantitative differences in epoxide levels were observed. The results indicate that human liver tissue is exposed in vitro to smaller concentrations of the primary metabolite 2-methyl-1,2-epoxypropane than rodent liver.

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“…Hydrolysis of 1,2-epoxy-2-methylpropane to 2-methyl-1,2-propanediol occurs in mammalian systems where epoxide hydrolases are common (55)(56)(57). 2-Hydroxyisobutyrate has also been detected as a mammalian metabolite of 2-methylpropene oxidation (58).…”

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Metabolism of 2-Methylpropene (Isobutylene) by the Aerobic Bacterium Mycobacterium sp. Strain ELW1

Kottegoda

Waligora

Hyman

2015

Appl Environ Microbiol

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An aerobic bacterium (Mycobacterium sp. strain ELW1) that utilizes 2-methylpropene (isobutylene) as a sole source of carbon and energy was isolated and characterized. Strain ELW1 grew on 2-methylpropene (growth rate ‫؍‬ 0.05 h ؊1 ) with a yield of 0.38 mg (dry weight) mg 2-methylpropene ؊1 . Strain ELW1 also grew more slowly on both cis-and trans-2-butene but did not grow on any other C 2 to C 5 straight-chain, branched, or chlorinated alkenes tested. Resting 2-methylpropene-grown cells consumed ethene, propene, and 1-butene without a lag phase. Epoxyethane accumulated as the only detected product of ethene oxidation. Both alkene consumption and epoxyethane production were fully inhibited in cells exposed to 1-octyne, suggesting that alkene oxidation is initiated by an alkyne-sensitive, epoxide-generating monooxygenase. Kinetic analyses indicated that 1,2-epoxy-2-methylpropane is rapidly consumed during 2-methylpropene degradation, while 2-methyl-2-propen-1-ol is not a significant metabolite of 2-methylpropene catabolism. Degradation of 1,2-epoxy-2-methylpropane by 2-methylpropene-grown cells led to the accumulation and further degradation of 2-methyl-1,2-propanediol and 2-hydroxyisobutyrate, two sequential metabolites previously identified in the aerobic microbial metabolism of methyl tert-butyl ether (MTBE) and tert-butyl alcohol (TBA). Growth of strain ELW1 on 2-methylpropene, 1,2-epoxy-2-methylpropane, 2-methyl-1,2-propanediol, and 2-hydroxyisobutyrate was fully inhibited when cobalt ions were omitted from the growth medium, while growth on 3-hydroxybutyrate and other substrates was unaffected by the absence of added cobalt ions. Our results suggest that, like aerobic MTBE-and TBA-metabolizing bacteria, strain ELW1 utilizes a cobalt/cobalamin-dependent mutase to transform 2-hydroxyisobutyrate. Our results have been interpreted in terms of their impact on our understanding of the microbial metabolism of alkenes and ether oxygenates.T he compound 2-methylpropene (isobutylene) is one of four butene (C 4 H 8 ) isomers and is the simplest branched alkene. Annually, in excess of 10 million tons of this gas are produced worldwide, mainly from cracking of petroleum. 2-Methylpropene is used as feedstock for high-volume petrochemicals, including ether fuel oxygenates, such as methyl tert-butyl ether (MTBE); high-octane gasoline blending components, such as 2,2,4-trimethylpentane (isooctane); and butyl rubber (1). The industrial importance of 2-methylpropene has stimulated interest in its biological production as an alternative to nonrenewable petroleum sources. Many microorganisms that can generate this gas have been identified (2, 3), including MTBE-metabolizing bacteria (4). It can also be produced directly by several enzymes (5-8). In contrast to these microbial and enzymatic production routes, little is known about the microbial degradation of 2-methylpropene, and no microorganisms have previously been reported to grow on this gas.From their outset, studies of aerobic microbial metabolism of gaseous alkenes have f...

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In vitro biotransformation of 2-methylpropene (isobutene): Epoxide formation in mice liver

Cited by 9 publications

References 24 publications

Breath biomarkers of liver cirrhosis

Breath biomarkers of liver cirrhosis

Species-Dependent Differences in Biotransformation Pathways of 2-Methylpropene (Isobutene)

Metabolism of 2-Methylpropene (Isobutylene) by the Aerobic Bacterium Mycobacterium sp. Strain ELW1

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