Terminal metabolites

Microbial activity may produce reactive intermediates that undergo spontaneous chemical transformation to terminal metabolites. This is quite a frequent occurrence, and its diversity is illustrated by the following examples ... 

Initially formed polar metabolites such as phenols and amines may be conjugated to water-soluble terminal metabolites that are excreted into the medium and function as an effective mechanism of detoxification. For example, pentachlorophenol and pentachlorothiophenol produced from pentachloronitrobenzene conjugated represented the major metabolites. Although the naphthalene dihydrodiol was the major metabolite produced from naphthalene, the further transformation... 

In most of the above illustrations, quinones have been formed and they may be terminal metabolites or only transient intermediates that are produced, for example, during mineralization by the basiomycete Stropharia coronillla (Steffen et al. 2003). Degradation was stimulated by addition of Mn +, and conld be attributed to elevated levels of the lignolytic manganese peroxidase. Experiments with Ph. laevis strain HHB-1625 have revealed some additional features (Bogan and Lamar 1996) ... 

The metabolism of cinnamate and w-phenylalkane carboxylates has been studied in Rhodopseudomonaspalustris (Elder et al. 1992), and for growth with the higher homologs additional CO2 was necessary. The key degradative reaction was ()-oxidation, for compounds with chain lengths of three, five, and seven carbon atoms, benzoate was formed and further metabolized, but for the even-numbered compounds with four, six, and eight carbon atoms phenylacetate was a terminal metabolite. 

It can be concluded from these observations that whereas benzoate produced by the carboxylation of phenols can be degraded, dehydroxylation with the formation of substituted benzoates may produce stable terminal metabolites. 

Dichloro from the 2 3 position with loss of chloride, to the 3,4-dihydrodiol that is a terminal metabolite... 

Although fluorotoluenes have yielded the corresponding fluorobenzoates, these reactions are merely biotransformations since the fluorobenzoates are terminal metabolites ... 

Both trifluoromethylbenzoates and trifluoromethylphenols prodnced 2-hydroxy-6-keto-7,7,7-trifluorohepta-2,4-dienoate, which is the immediate ring-fission prodnct. The triflnoromethyl group of the original substrates was retained in the terminal metabolites. 

V-acetylation to neutral acetanilides that are terminal metabolites (Noguera and Freedman 1996)... 

Chloro-2-hydroxypyridine-3-carboxylate is a terminal metabolite in the degradation of 3-chloroquinoline-8-carboxylate, but can be degraded by Mycobacterium sp. strain BA to chlorofumarate by reactions analogous to those described above for pyridine carboxylates (Figure 10.18) (Tibbies et al. 1989a). 

In addition, the formation of terminal metabolites may be adverse either for the organism itself, or for other organisms in the ecosystem. Microbial metabolites may also undergo purely chemical reactions to compounds that are terminal products. Examples include the formation of 5-hydroxyquinoline-2-carboxylate from 5-aminonaphthalene-2-sulfonate (Nortemann et al. 1993) or benzo[fc]naphtho[l,2- /]thiophene from benzothiophene (Kropp et al. 1994). Microbial metabolites may be toxic to both the bacteria producing them and to higher organisms. Illustrative examples of toxicity include the following ... 

Diminution in the concentration of the substrate(s) is not alone an acceptable measure of degradation, since loss may occur by volatilization or by transformation with the formation of transient or terminal metabolites. In addition there may be a continuous input, for... 

Microbial 0-methylation to chloroanisoles may occur, and under aerobic conditions these may be terminal metabolites. As a result of their lipophilic character they may be transported into higher biota and hence into the food chain via earthworms (Palm et al. 1991). 

Although the possibility of bioremediation of sites contaminated with nitrotoluene waste is clearly possible, important issues should be clearly appreciated. These include (a) additional carbon sources may be necessary to accomplish partial or complete reduction of nitro groups, (b) under aerobic conditions, dimeric azo compounds may be formed as terminal metabolites, and (c) aromatic amines may be incorporated into humic material by covalent bonding and thereby resist further degradation. 

Examination of pathways including transformation with the formation of intermediate and terminal metabolites... 

DFBcPh and its dihydrodiol were subjected to metabolism, and the extent of DNA binding in human breast cancer MCF-7 cells was assessed." The extent of DNA binding was then compared with that for BcPh and its dihydrodiol and the potent carcinogen BaP. The 1,4-DFBcPh series 2 (anti) DE-derived DNA adducts were also compared with those arising from intracellular oxidation of the dihydrodiol with subsequent DNA binding. These experiments showed that increased molecular distortion decreased metabolic activation to the terminal metabolites but the DE metabolites formed were the DNA-damaging species. 

---