The role of arene oxide-oxepin systems in the metabolism of aromatic substrates. III. Formation of 1,2-naphthalene oxide from naphthalene by liver microsomes

Jerina, Donald M.; Daly, John W.; Witkop, Bernhard; Zaltzman-Nirenberg, Perola; Udenfriend, Sidney

doi:10.1021/ja01025a058

Cited by 231 publications

(91 citation statements)

References 1 publication

(1 reference statement)

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“…The intermediate finally aromatizes to form a phenol (10,19). Stable arene oxides of naphthalene, quinoline, and methylbenzoate have been isolated as metabolic intermediates during enzyme-catalyzed hydroxylation of these compounds (1,11,45,46). Consequently, as well as providing a mechanistic explanation for the NIH shift, there is direct evidence that arene oxides are intermediates in the enzymatic hydroxylation of at least some aromatic compounds containing one or more aromatic rings.…”

Section: Discussionmentioning

confidence: 99%

Aerobic Metabolism of 4-Hydroxybenzoic Acid in Archaea via an Unusual Pathway Involving an Intramolecular Migration (NIH Shift)

Fairley

Boyd

Sharma

et al. 2002

Appl Environ Microbiol

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A novel haloarchaeal strain, Haloarcula sp. strain D1, grew aerobically on 4-hydroxybenzoic acid (4HBA) as a sole carbon and energy source and is the first member of the domain Archaea reported to do so. Unusually, D1 metabolized 4HBA via gentisic acid rather than via protocatechuic acid, hydroquinone, or catechol. Gentisate was detected in 4HBA-grown cultures, and gentisate 1,2-dioxygenase activity was induced in 4HBA-grown cells. Stoichiometric accumulation of gentisate from 4HBA was demonstrated in 4HBA-grown cell suspensions containing 2,2-dipyridyl (which strongly inhibits gentisate 1,2-dioxygenase). To establish whether initial 1-hydroxylation of 4HBA with concomitant 1,2-carboxyl group migration to yield gentisate occurred, 2,6-dideutero-4HBA was synthesized and used as a substrate. Deuterated gentisate was recovered from cell suspensions and identified as 3-deutero-gentisate, using gas chromatography-mass spectrometry and proton nuclear magnetic resonance spectroscopy. This structural isomer would be expected only if a 1,2-carboxyl group migration had taken place, and it provides compelling evidence that the 4HBA pathway in Haloarcula sp. strain D1 involves a hydroxylation-induced intramolecular migration. To our knowledge, this is the first report of a pathway which involves such a transformation (called an NIH shift) in the domain Archaea.

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Section: Discussionmentioning

confidence: 99%

Aerobic Metabolism of 4-Hydroxybenzoic Acid in Archaea via an Unusual Pathway Involving an Intramolecular Migration (NIH Shift)

Fairley

Boyd

Sharma

et al. 2002

Appl Environ Microbiol

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“…Previous studies on the mechanism of mercapturic acid and dihydrodiol formation both in vivo and in liver preparations have led to the view that a number of aromatic hydrocarbons are intially converted to epoxides by liver microsomes (11,12); indeed, direct proof for the formation of napththalene epoxide was recently obtained by Jerina et al (13,14). According to the current view, the epoxides are then converted nonenzymatically to phenols or enzymatically to their GSH conjugates and dihydrodiol derivatives (15,16).…”

Section: Histologic Studiesmentioning

confidence: 98%

Possible Mechanism of Liver Necrosis Caused by Aromatic Organic Compounds

Brodie

Reid

Cho

et al. 1971

Proc. Natl. Acad. Sci. U.S.A.

321

124

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Treatment of rats with phenobarbital, which stimulates the activity of the drug-metabolizing enzymes in the liver, potentiates hepatic necrosis elicited by bromobenzene and a number of other chemically inert halogenated aromatic hydrocarbons. Radioautographic studies indicate that ['4Clbromobenzene is covalently bound at the sites of necrosis. From these results, it is inferred that the hepatotoxic effects of the halogenated aromatic hydrocarbons are mediated by chemically active metabolites formed in hepatocytes. In accord with this view, a number of aromatic halogenated hydrocarbons are converted by microsomes in vitro to active intermediates which form covalent complexes with glutathione (GSH).

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“…The consequences of such reactions result in the production of intermediates containing epoxide, phenol, or cis-dihydrodiol functional groups that correspond to the parent aromatic compound from which it was derived (6,10,14,21,27,28,45). Based upon whether a eukaryote or prokaryote is performing the activity ( Fig.…”

mentioning

confidence: 99%

Epoxide Formation on the Aromatic B Ring of Flavanone by Biphenyl Dioxygenase of Pseudomonas pseudoalcaligenes KF707

Han

Kim

Jung

et al. 2005

Appl Environ Microbiol

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Prokaryotic dioxygenase is known to catalyze aromatic compounds into their corresponding cis-dihydrodiols, however, we found that the same enzyme showed dioxygenase activity toward flavone, resulting in the production of flavone cis-2,3-dihydrodiol. Extensive structural identification of the metabolites of flavanone by using high-pressure liquid chromatography, liquid chromatography/mass spectrometry, and nuclear magnetic resonance confirmed the presence of an epoxide functional group on the metabolites. Epoxide formation as the initial activation step of aromatic compounds by oxygenases has been reported to occur only by eukaryotic monooxygenases. To the best of our knowledge, biphenyl dioxygenase from P. pseudoalcaligenes KF707 is the first prokaryotic enzyme detected that can produce an epoxide derivative on the aromatic ring structure of flavanone.

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The role of arene oxide-oxepin systems in the metabolism of aromatic substrates. III. Formation of 1,2-naphthalene oxide from naphthalene by liver microsomes

Cited by 231 publications

References 1 publication

Aerobic Metabolism of 4-Hydroxybenzoic Acid in Archaea via an Unusual Pathway Involving an Intramolecular Migration (NIH Shift)

Aerobic Metabolism of 4-Hydroxybenzoic Acid in Archaea via an Unusual Pathway Involving an Intramolecular Migration (NIH Shift)

Possible Mechanism of Liver Necrosis Caused by Aromatic Organic Compounds

Epoxide Formation on the Aromatic B Ring of Flavanone by Biphenyl Dioxygenase of Pseudomonas pseudoalcaligenes KF707

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