The Metabolism of Naphthalenes

Naphthalene-1,2-oxide is the obligatory intermediate in the microsomal hydroxyl-ation of naphthalene to 1-naphthol, 2-dihydroxy-1,2-dihydronaphthalene 

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This is illustrated by the metabolism of naphthalene, labeled in the 1 position with deuterium (2H), via the 1,2-oxide as shown in Figure 4.5. The shift in the deuterium atom that occurs during metabolism is the so-called NIH shift. This indicates that formation of an epoxide intermediate has occurred, and is one method of determining whether such an epoxide intermediate is involved. The phenolic products, 1- and 2-naphthols, retain various proportions of deuterium, however. The proposed mechanism involves the formation of an epoxide intermediate, which may break open chemically in two ways, leading to phenolic products (Fig. 4.5). 

Figure 5.4 The metabolism of naphthalene showing the various possible isomeric glutathione conjugates.

Treccani, V., Walker, N. Wiltshire, G. H. (1954). The metabolism of naphthalene by soil bacteria. Journal of General Microbiology, 11, 341-8. 

The metabolism of naphthalene is similar to that of benzene, starting with an enzymatic epoxidation of the aromatic ring ... 

Of the MAP metabolites tested in vitro, the enzymes studied to date have a specificity for L-cystelne conjugates. A preMAP metabolite (the cysteine conjugate of naphthalene) has been tested only in microorganisms (61) and was a substrate. Tissue C-S lyase exhibits an additional specificity for cysteine conjugates in which the carbon of the xenobiotic moiety attached to the cysteine sulfur be unsaturated (vinyl or aromatic), therefore preMAP metabolites, which lack this aromaticity, should not be substrates for tissue C-S lyase. In vivo evidence that this is the case was obtained in the metabolism of naphthalene (11). C-S lyases associated with the Intestinal microflora, which may involve many different enzymes in a number of different microorganisms, do not exhibit this specificity for aromatic compounds. 

The transformation of a few polycyclic aromatic hydrocarbons has also been investigated in yeasts. The metabolism of naphthalene, biphenyl, and benzo [a] pyrene has been examined in a strain of Debaryomyces hansenii and in number of strains of Candida sp. The results using C. lipolytica showed that the transformations were similar to those carried out by fungi the primary reaction was formation of the epoxides that were then rearranged to phenols (Cerniglia and Crow 1981). Benzo[a]pyrene is transformed by Saccharomyces cerevisiae to the 3- and 9-hydroxy compounds and the 9,10-dihydrodiol, and the cytochrome P-448 that mediates the monooxygenation has been purified and characterized (King et al. 1984). 

Corner EDS, Leon YA, Bulbrook RD (1960) Steroid sulphatase, arylsulphatase and /S-glucuronidase in marine invertebrates. J Mar Biol Assoc UK 39 51-61 Corner EDS, Kilvington CC, O Hara SCM (1973) Qualitative studies on the metabolism of naphthalene in Maia squinado (Herbst). J Mar Biol Assoc UK 53 819-832 Corner EDS, Harris RP, Kilvington CC, O Hara SCM (1976) Petroleum compounds in the marine food web short-term experiments on the fate of naphthalene in Calanus. J Mar Biol Assoc UK 56 121-133... 

This enzyme catalyses a conjugation reaction known to be involved in the metabolism of naphthalene. 

Salicylate is an intermediate in the metabolism of PAHs including naphthalene and phen-anthrene, and its degradation involves oxidation to catechol. The hydroxylase (monooxygenase) has been extensively studied (references in White-Stevens and Kamin 1972) and in the presence of an analog that does not serve as a substrate, NADH is oxidized with the production of H2O2 (White-Stevens and Kamin 1972). This uncoupling is characteristic of flavoenzymes and is exemplified also by the chlorophenol hydroxylase from an Azotobacter sp. that is noted later. 

Zhang X, LY Young (1997) Carboxylation as an initial reaction in the anaerobic metabolism of naphthalene and phenanthrene by sulfidogenic consortia. Appl Environ Microbiol 63 4759-4764. 

FIGU RE 8.1 Alternative pathways for the oxidative metabolism of naphthalene by (a) bacteria and (b) fungi. 

Cerniglia CE, JR Althus, EE Evans, JP Freeman, RK Mitchum, SK Yang (1983) Stereochemistry and evidence for an arene oxide-NIH shift pathway in the fungal metabolism of naphthalene. Chem-Biol Interactions 44 119-132. 

Wilson and Madsen [152] used the metabolic pathway for bacterial naphthalene oxidation as a guide for selecting l,2-dihydroxy-l,2-dihydronaphthalene as a unique transient intermediary metabolite whose presence in samples from a contaminated field site would indicate active in situ naphthalene biodegradation (Fig. 26). Naphthalene is a component of a variety of pollutant mixtures. It is the major constituent of coal tar [345], the pure compound was commonly used as a moth repellant and insecticide [345], and it is a predominant constituent of the fraction of crude oil used to produce diesel and jet fuels [346]. Prior studies at a coal tar-contaminated field site have focused upon contaminant transport [10,347], the presence of naphthalene catabolic genes [348, 349], and non-metabolite-based in situ contaminant biodegradation [343]. 

If PAH-degrading microorganisms use broad-specificity enzymes or common pathways to transform multiple PAHs, then inducers for the metabolism of one PAH substrate might co-induce the transformation of a range of PAHs. Preliminary evidence indicated that the transformation of naphthalene, phenanthrene, fluoranthene, and pyrene by Pseudomonas saccharophila P15 was stimulated by salicylate [132], a known inducer of naphthalene metabolism in pseudomonads [43]. However, Chen and Aitken [181] reported in more detail the inducing effects of salicylate on the transformation of various HMW PAHs by Pseudomonas saccharophila P15 isolated from contaminated soil, including... 

The oxidation of naphthalene was one of the earliest examples of an epoxide as an intermediate in aromatic hydroxylation. The epoxide can rearrange nonenzymatically to yield predominantly 1-naph-thol, interact with the enzyme epoxide hydrolase to yield the dihydrodiol, or interact with glutathione S-transferase to yield the glutathione conjugate, which is ultimately metabolized to a mer-capturic add. 

Catterall, F. A., Murray, K. Williams, P. A. (1971). The configuration of the l,2-dihydroxy-l,2-dihydronaphthalene formed by the bacterial metabolism of naphthalene. Biochimica et Biophysica Acta, 237, 361-4. 

Cerniglia, C. E., Van Baalen, C. Gibson, D. T. (1980a). Metabolism of naphthalene by the cyanobacterium Oscillatoria sp., strain CM. Journal of General Microbiology, 116,485-95. 

Davies, J. I. Evans, W. C. (1964). Oxidative metabolism of naphthalene by soil pseudomonads The ring-fission mechanism. Biochemical Journal, 91, 231-61. 

Kuhm, A. E., Stoiz, A. Knackmuss, H.J. (1991). Metabolism of naphthalene by the biphenyl-degrading bacterium PseudomonaspaucimobdisCJV. Biodegradation, 2,115-20. 

The mechanism of the NIH shift was not clearly understood until naphthalene 1,2-oxide (197) was isolated in the metabolism of 1-T-naphthalene (198) with hepatic monoxygenases the oxide then rearranges to 1-naphthol with migration of tritium from the 1- to the 2-position.112,113... 

Naphthalene-1,2-oxide is a metabolic intermediate in the oxidation of naphthalene mediated by cytochrome P-450. 

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