Aromatic compounds metabolism

Heterocyclic enamines A -pyrroline and A -piperideine are the precursors of compounds containing the pyrrolidine or piperidine rings in the molecule. Such compounds and their N-methylated analogs are believed to originate from arginine and lysine (291) by metabolic conversion. Under cellular conditions the proper reaction with an active methylene compound proceeds via an aldehyde ammonia, which is in equilibrium with other possible tautomeric forms. It is necessary to admit the involvement of the corresponding a-ketoacid (12,292) instead of an enamine. The a-ketoacid constitutes an intermediate state in the degradation of an amino acid to an aldehyde. a-Ketoacids or suitably substituted aromatic compounds may function as components in active methylene reactions (Scheme 17). 

Oxepin and its derivatives have attracted attention for several reasons. Oxepin is closely related to cycloheptatriene and its aza analog azepine and it is a potential antiaromatic system with 871-elcctrons. Oxepin can undergo valence isomerization to benzene oxide, and the isomeric benzene oxide is the first step in the metabolic oxidation of aromatic compounds by the enzyme monooxygenase. 

The metabolic processes underpinning the catabolism of aliphatic and aromatic compounds are described in the BIOTOL text "Energy Sources for Cell". 

JV-Acetyltransferases (NATs) catalyze the conjugation of an acetyl group from acetyl-CoA on to an amine, hydrazine or hydroxylamine moiety of an aromatic compound. NATs are involved in a variety of phase II-diug metabolizing processes. There are two isozymes NAT I and NAT II, which possess different substrate specificity profiles. The genes encoding NAT I and NAT II are both multi-allelic. Especially for NAT II, genetic polymoiphisms have been shown to result in different phenotypes (e.g., fast and slow acetylators). 

Nelson MJK, Montgomery SO, Pritchard PH. 1988. Trichloroethylene metabolism by microorganisms that degrade aromatic compounds. Appl Environ Microbiol 54 604-606. 

The anaerobic biotransfonnation of aromatic compounds may be dependent on COj, and a review by Ensign et al. (1998) provides a brief summary of the role of CO2 in the metabolism of epoxides by Xanthobacter sp. strain Py2, and of acetone by both aerobic and anaerobic bacteria. 

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... 

Analogous ring fission reactions have also been found in stndies on the metabolism of other aromatic compounds by the yeast Trichosporon cutaneum whose metabolic versatility is indeed comparable with that of bacteria. Examples inclnde the degradation of... 

Important investigations have been directed to persistent halogenated aromatic compounds and different mechanisms for their metabolism have been found ... 

Nozawa T, Y Maruyama (1988) Anaerobic metabolism of phthalate and other aromatic compounds by a denitrifying bacterium. J Bacteriol 170 5778-5784. 

Harwood CS, G Burchardt, H Herrmann, G Fuchs (1999) Anaerobic metabolism of aromatic compounds via the benzoyl-CoA pathway. FEMS Microbiol Rev 22 439-458. 

The signiflcance of toxic metabolites is important in diverse metabolic situations (a) when a pathway results in the synthesis of a toxic or inhibitory metabolite, and (b) when pathways for the metabolism of two (or more) analogous substrates supplied simultaneously are incompatible due to the production of a toxic metabolite by one of the substrates. A number of examples are provided to illustrate these possibilities that have achieved considerable attention in the context of the biodegradation of chlorinated aromatic compounds (further discussion is given in Chapter 9, Part 1) ... 

Dangel W, R Brackmann, A Lack, M Mohamed, J Koch, J Oswald, B Seyfried, A Tschech, G Fnchs (1991) Differential expression of enzyme activities initiating anoxic metabolism of varions aromatic compounds via benzoyl-CoA. Arch Microbiol 155 256-262. 

Daly JW, DM Jerina, B Witkop (1972) Arene oxides and the NIH shift the metabolism, toxicity and carcinogenicity of aromatic compounds. Experientia 28 1129-1149. 

Several pathways are used for the aerobic degradation of aromatic compounds with an oxygenated C2 or C3 side chain. These include acetophenones and reduced compounds that may be oxidized to acetophenones, and compounds including tropic acid, styrene, and phenylethylamine that can be metabolized to phenylacetate, which has already been discussed. 

Heider J et al. (1998) Differential induction of enzymes involved in anaerobic metabolism of aromatic compounds in the denitrifying bacterium Thauera aromatica. Arch Microbiol 170 120-131. 

Compared with monocyclic aromatic hydrocarbons and the five-membered azaarenes, the pathways used for the degradation of pyridines are less uniform, and this is consistent with the differences in electronic structure and thereby their chemical reactivity. For pyridines, both hydroxylation and dioxygenation that is typical of aromatic compounds have been observed, although these are often accompanied by reduction of one or more of the double bonds in the pyridine ring. Examples are used to illustrate the metabolic possibilities. 

In the absence of molecular oxygen, a nnmber of alternative electron acceptors may be used these include nitrate, sulfate, selenate, carbonate, chlorate, Fe(III), Cr(VI), and U(VI), and have already been discussed in Chapter 3, Part 2. In Chapter 14, which deals with applications, attention is directed primarily to the role of nitrate, sulfate, and Fe(III)— with only parenthetical remarks on Cr(VI) and U(VI). The role of nitrate and sulfate as electron acceptors for the degradation of monocyclic aromatic compounds is discnssed, and the particularly broad metabolic versatility of sulfate-reducing bacteria is worthy of notice. 

Reviews on the microbial metabolism of hydrocarbons with biochemical aspects are available, and inclnde those of Britton (1984) on alkanes, and of Morgan and Watkinson (1994) that also includes cycloalkanes and some aromatic compounds. Virtually all the issues that are discussed in these recur in the examples that are used as illustration. Some broad generalizations are summarized ... 

Phenols also constitute a major source of xenobiotic exposure to the body in the form of drugs and environmental pollutants. Oxidative metabolism of these compounds can lead to physiological damage, therefore the metabolism of these compounds is of great interest. LCEC has been a powerful tool for investigating the metabolism of aromatic compounds by the cytochrome P-450 system LCEC... 

If an aromatic compound reacts with an OH radical to form a specific set of hydroxylated products that can be accurately identified and quantified in biological samples, and one or more of these products are not identical to naturally occurring hydroxylated species, i.e. not produced by normal metabolic processes, then the identification of these unnatural products can be used to monitor OH radical activity therein. This is likely to be the case if the aromatic detector molecule is present at the sites of OH radical generation at concentrations sufficient to compete with any other molecules that might scavenge OH radical. 

Berry DF, Francis AJ, Bollag J-M (1987) Microbial metabolism of homocyclic and heterocyclic aromatic compounds under anaerobic conditions. Micorbiol Rev 51 43-59... 

Heider J, Fuchs G (1997) Anaerobic metabolism of aromatic compounds. Eur J Biochem 243 577-596... 

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