Catechol, metabolism

Barnsley EA (1976) Role and regulation of the ortho and meta pathways of catechol metabolism in pseudomonads metabolizing naphthalene and salicylate. J Bacteriol 125 404-408. 

Isoproterenol is given sublingually or by iv. It is metabolized by monoamine oxidase and catechol-0-methyltransferase in brain, Hver, and other adrenergically innervated organs. The pharmacological effects of isoproterenol are transient because of rapid inactivation and elimination. About 60% is excreted unchanged. Adverse effects using isoproterenol therapy include nervousness, hypotension, weakness, dizziness, headache, and tachycardia (86). 

The principal mechanism for terminating dopamine signaling is reuptake by the presynaptic neuron via the dopamine transporter (DAT). Dopamine that is not taken up is metabolized by the enzymes monoamine oxidase (MAO) and catechol-O-methyl transferase... 

Metabolic pathways containing dioxygenases in wild-type strains are usually related to detoxification processes upon conversion of aromatic xenobiotics to phenols and catechols, which are more readily excreted. Within such pathways, the intermediate chiral cis-diol is rearomatized by a dihydrodiol-dehydrogenase. While this mild route to catechols is also exploited synthetically [221], the chirality is lost. In the context of asymmetric synthesis, such further biotransformations have to be prevented, which was initially realized by using mutant strains deficient in enzymes responsible for the rearomatization. Today, several dioxygenases with complementary substrate profiles are available, as outlined in Table 9.6. Considering the delicate architecture of these enzyme complexes, recombinant whole-cell-mediated biotransformations are the only option for such conversions. E. coli is preferably used as host and fermentation protocols have been optimized [222,223]. 

Just as the synthesis of DA and NA is similar so is their metabolism. They are both substrates for monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT). In the brain MAO is found in, or attached to, the membrane of the intraneuronal mitochondria. Thus it is only able to deaminate DA which has been taken up into nerve endings and blockade of DA uptake leads to a marked reduction in the level of its deaminated metabolites and in particular DOPAC. The final metabolite, homovanillic... 

After reuptake into the cytosol, some noradrenaline may be taken up into the storage vesicles by the vesicular transporter and stored in the vesicles for subsequent release (see above). However, it is thought that the majority is broken down within the cytosol of the nerve terminal by monoamine oxidase (MAO ECl.4.3.4). A second degradative enzyme, catechol-O-methyl transferase (COMT EC2.1.1.6), is found mostly in nonneuronal tissues, such as smooth muscle, endothelial cells or glia. The metabolic pathway for noradrenaline follows a complex sequence of alternatives because the metabolic product of each of these enzymes can act as a substrate for the other (Fig 8.8). This could enable one of these enzymes to compensate for a deficiency in the other to some extent. 

HT is metabolised primarily by MAO to 5-hydroxyindoleacetic acid (5-HIAA) (Fig. 9.4). In vitro, 5-HT is the preferred substrate for the MAOa, rather than the MAOb isoenzyme (see Chapter 8) and this appears to be the case in vivo since MAOa, but not MAOb, knock-out mice have increased concentrations of 5-HT in the brain. Obviously, because of its indole nucleus, 5-HT is not a substrate for the enzyme COMT which metabolises the catechol derivatives, dopamine and noradrenaline. However, other metabolic products of 5-HT are theoretically possible and one, 5-hydroxytryptophol,... 

Catechol-O-methyltransferase (COMT EC 2.1.1.6) is located in many tissues and catalyzes the methylation of polyphenols. The methylation is a well-established pathway in the metabolism of flavonoids such as those that undergo 3, 4 -dihydrox-ylation of ring B excreted as 3 -0-methyl ether metabohtes in rat bile. " Recently, the apparent methylation of both cyanidin-3-glucoside and cyanidin-3-sambubioside (cyanidin is an anthocyanin with a 3, 4 -dihydroxylation of ring B) to peonidin-3-glucoside and peonidin-3-sambubioside was reported in humans. In rats, this transformation occurred mainly in the liver and was catalyzed by COMT."°... 

Zhang et al. isolated Clostridium hydroxybenzoicum containing two inducible 4-hydroxybenzoate decarboxylase and 3,4-dihydroxybenzoate decarboxylase that form phenol and catechol (1,2-dihydroxybenzene), respectively. The organism does not further metabolize phenol and catechol produced by these reactions. The carboxylation activities of the two purified decarboxylases are not... 

Rhizobia. Taxa belonging to both the genera Rhizobium and Bradyrhizobium are capable of degrading simple aromatic compounds including benzoate (Chen et al. 1984) and 4-hydroxy-benzoate (Parke and Omston 1986 Parke et al. 1991). It has been shown that 4-hydroxyben-zoate hydroxylase is required for the transport of 4-hydroxybenzoate into the cell (Wong et al. 1994). In strains of Rhizobium trifolium, the metabolism of benzoate involves either 3,4-dihydroxybenzoate (protocatechuate) 3,4-dioxygenase (Chen et al. 1984), or catechol... 

The metabolic activity of other white-rot fungi including Phanerochaete chrysosporium and Pleurotus ostreacus has been discussed in the context of polycyclic aromatic hydrocarbons. For example, the mineralization potential of the manganese peroxide system fmmNematolomafrowardii for a number of substrates has been demonstrated (Hofrichter et al. 1998) the formation of CO2 from labeled substrates ranged from 7% (pyrene) to 36% (pentachlorophenol), 42% (2-amino-4, 6-dinitrotoluene), and 49% (catechol). 

Chen, YP, AR Glenn, MJ Dilworth (1985) Aromatic metabolism in Rhizobium trifolii—catechol 1,2-dioxy-genase. Arch Microbiol 141 225-228. 

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. 

The metabolism of C-labeled BTX has been examined in soil cultures, and a mass balance constructed after 4 weeks of aerobic incubation (Tsao et al. 1998). Mineralization of all substrates was ca. 70% but ca. 20% of the label in toluene and ca. 30% in o-xylene were found in humus. It was suggested that alkylated catechol metabolites were responsible for this association. 

Heavy-metal cations and oxyanions are generally toxic to bacteria although resistance may be induced by various mechanisms after exposure. Attention is drawn to an unusual example in which AF+ may be significant, since the catechol 1,2-dioxygenase and 3,4-dihydroxybenzoate (protocat-echuate) 3,4-dioxygenase that are involved in the metabolism of benzoate by strains of Rhizobium trifolii are highly sensitive to inhibition by AP (Chen et al. 1985). 

The metabolism of fluorophenols by phenol hydroxylase from Trichosporium cutaneum, catechol 1,2-dioxygenase from Pseudomonas arvilla strain C-1, and by the fungus Exophilia jeanselmei has been examined, and detailed NMR data were given for the ring fission flnoromnconates (Boersma et al. 1998). 

The degradation of 2,2 -dihydroxy- 3,3 -dimethoxybiphenyl-5,5 -dicarboxylate (5,5 -dehydro-divanillate) by Sphingomonas paucimobilis SYK-6 proceeds by partial de-O-methylation followed by extradiol hssion of the catechol to 2-hydroxy-3-methoxy-5-carboxybenzoate. Diversion of this into central metabolic pathways involves decarboxylation to vanillate by two separate decarboxylases LigWl and LigW2 (Peng et al. 2005). 

The mandelate pathway in Pseudomonas putida involves successive oxidation to benzoyl formate and benzoate, which is further metabolized via catechol and the 3-ketoadipate pathway (Figure 8.35a) (Hegeman 1966). Both enantiomers of mandelate were degraded through the activity of a mandelate racemase (Hegeman 1966), and the racemase (mdlA) is encoded in an operon that includes the next two enzymes in the pathway—5-mandel-ate dehydrogenase (mdlB) and benzoylformate decarboxylase (mdlC) (Tsou et al. 1990). 

A two-component 2-halobenzoate 1,2-dioxygenase has been purified from Pseudomonas cepacia strain 2CBS that is able to metabolize 2-fluorobenzoate, 2-chlorobenzoate, 2-bromobenzoate, and 2-iodobenzoate to catechol by concomitant decarboxylation and loss of halide (Fetzner et al. 1992). The inducible 2-halobenzoate 1,2-dioxygenase consisted of... 

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