Metabolism proposed pathway

The proposed pathways for methyl-substituted quinolines differ from those shown in Fig. 23, even for the same culture, and most particularly, the fact that no C—N bond cleavage has been observed in most of the strains. A limited number of methylquinolines can be hydroxylated due to the inhibiting and blocking effect of the methyl group, particularly at position 2. So, neither P. aeruginosa QP nor P. putida QP could metabolize 2-methylquinoline however, a new strain of Pseudomonas (MQP) isolated by Grant and Al-Najjar [328] was reported to be able to transform 2-methylquinoline, yielding... 

Proposed pathways for the metabolism of acrylonitrile are presented in Figure 2-3 (Ahmed et al. 

Figure 22.2 Proposed pathway of paraquat degradation by a bacterial isolate (upper) and by ultraviolet irradiation (lower). (Modified from Funderburk, H.H., Jr. and G.A. Bozarth. 1967. Review of the metabolism and decomposition of diquat and paraquat. Jour. Agric. Food Chem. 15 563-567.

The major biotransformations of pseudoephedrine hydrochloride are parahydroxylation, N-demethylation, and oxidative deamination.14 The proposed pathways for the metabolism of pseudoephedrine are shown in Figure 6. 

The metabolism of 77-hexane takes place in the liver. The initial reaction is oxidation by cytochrome P-450 isozymes to hexanols, predominantly 2-hexanol. Further reactions convert 2-hexanol to 2-hexanone, 2,5-hexanediol, 5-hydroxy-2-hexanone, 4,5-dihydroxy-2-hexanone and the neurotoxicant 2,5-hexanedione. Hydroxylation at the 1- and 3- positions can be considered detoxification pathways hydroxylation at the 2- position is a bioactivation pathway. A diagram of the proposed pathway for mammalian metabolism of -hexane is presented in Figure 2-3. 

FIGURE 2-2. Proposed Pathway of Metabolism of 1,3-DNB In Rats and Hamsters ... 

Levels of Significant Exposure to Hexachlorobutadiene - Inhalation 2-2 Levels of Significant Exposure to Hexachlorobutadiene - Oral 2-3 Proposed Pathways for Hexachlorobutadiene Metabolism ... 

Figure 1. Proposed pathway of diethanolamine metabolism in the rat, based on urinary excretion data from an eight-week oral dosing study (7 mg/kg bw per day, five days per week for eight weeks)...

The major advantage of an in vitro system is that it represents a simplified system which allows the experimenter to address questions which cannot be tested in vivo. These systems can allow analysis of activation or metabolism at the single enzyme level. They can test proposed pathways of metabolism or activation. Such studies are not practical with in vivo systems. The major disadvantage is that in vitro systems are a simplified system and the results can be easily over-interpreted. In vitro systems cannot model the pharmacokinetics or toxicokinetics of xenobiotic exposure in vivo. In addition, there may be other, unappreciated enzymes or factors which influence metabolism/toxicity in vivo which are not present in the in vitro system. 

There have been a few reports of aerobic bacterial species which will grow on dibenzothiophene as their sole carbon source (51,52)- However, most studies have focused on its co-metabolism (22,52,54) which appears to be a more common phenomenon. Intermediates of the biodegradation have been identified in a number of studies (55-57). Figure 10 is a simplification of the proposed pathway for dibenzothiophene metabolism showing the two endproducts 3-hydroxy-2-formylbenzothiophene (HFBT), which is the more abundant, and dibenzothiophene-sulfoxide. [For a more complete pathway see (56) or (58)1. This pathway shows 1,2-dihydroxydibenzothiophene as an intermediate and this is analogous to the diols found as intermediates of aromatic hydrocarbons. 

Figure 10. Simplification of the proposed pathways from dibenzothiophene co-metabolism by pure cultures of aerobic bacteria. (I) dibenzo-thiophene-sulfoxide, (II) 1,2-dihydroxydibenzothiophene, (III) 3-hydroxy-2-formylbenzothiophene.

Fig. 5.5. Proposed pathways of metabolism in Moniezia expansa scoleces under aerobic conditions cytosolic reactions. (After Bryant Behm, 1976.) OAA, oxaloacetate PYR, pyruvate, MAL, malate, LACT, lactate for other abbreviations, see the text.

Figure 9. Two proposed pathways for 2,4-DB metabolism by soil microorganisms...

A proposed pathway for the degradation of PCP by two bacterial strains is represented in Figure 10.9. Cultures of Pseudomonas were found to transform PCP into tetrachlorocatechol and tetrachlorohydroquinone (TeCHQ). These materials are then metabolized, and radiolabeled carbon can be found in the amino acids of the degradative bacteria. Mycobacterium methylates PCP to pentachloroanisole but does not use PCP as an energy source. Fungi also metabolize PCP to a less toxic metabolite. 

Figure 7. Proposed pathway of formation of l-(2,4-dichloro-phenyDethanol which is excreted in rats and dogs treated with dimethyIvinphos. In this case CSH is involved in metabolism but does not become a part of the structure of the urinary metabolite.

Figure 2. Proposed pathway for reductive defunctionalization (see text) and methylthio-group turnover observed in hexachlorobenzene metabolism.

Figure 4. Proposed pathway for metabolism of -dimethylaminobenzo-nitrile to a methyIsulfonyl containing acetanilide. Bracketed L J intermediates and processes are proposed. R= -NC(C 4)...

Proposed Pathway for Formation of Dimethyl Selenide from Selenite in Animals 3-6. Activation and Reduction of Selenate to Selenite in Yeast Saccharomyces cerevisiae 3-7. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a Hypothetical Chemical Substance 3-8. Selenite Model, a Kinetic Model for Selenite Metabolism 3-9. Selenomethionine Model, a Kinetic Model for Selenomethionine Metabolism 3-10.Existing Information on Health Effects of Selenium 6-1. Frequency of NPL Sites with Selenium Contamination... 

Liibben M, Kolmerer B, Saraste M (1992) On archaebacterial terminal oxidase combines core structures of two mitochondrial respiratory complexes. EMBO J 11 805-812 Lundgren DG, Silver M (1980) Ore leaching by bacteria. Annu Rev Microbiol 34 263-283 Lyric RM, Suzuki I (1970a) Enzyme involved in the metabolism of thiosulfate by Thiobacillus thioparus III. Properties of thiosulfate-oxidizing enzyme and proposed pathway of thiosulfate oxidation. Can J Biochem 48 355-363... 

Figure 5. Proposed Pathways of Ametryn Metabolism in the Rat (Continued)...

FIGURE 10.3 Proposed pathways for OA group toxin metabolism within algae. Enzymatic processes are shown by block arrows and striped arrows represent algal interactions. 

FIGURE 10.4 Proposed pathways for OA group toxin metabolism with shellfish. The block arrows represent relatively rapid processes whereas the dashed arrows are proposed slow processes. Intermediate metabolites... 

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