Xenobiotics biochemical pathways

Despite all the problems attendant on studies of aquatic animals, however, great strides have been made in the past 10 years in defining biochemical pathways used by fishes to biotransform and eliminate xenobiotics (2, 3, 4, 5). Many of the earlier studies, especially the extensive work of DeWaide (6), defined various biochemical transformations which xenobiotics may undergo in vitro. Only in the past 10 years have in vivo studies been undertaken to define the routes and rates of elimination of xenobiotics by fishes (7, 8, 9, 10, ll). 

Figure 14.1 Schematic of olfactory sensillum and a generalized biochemical pathway of odor reception. A An olfactory sensillum includes 2-3 neurons surrounded by 3 support cells olfactory dendrites/cilia project up the fluid filled lumen of a cuticular hair. The sensillum lumen is isolated from hemolymph by a cellular barrier. Modified from Steinbrecht (1969) see Steinbrecht (1999) for more details. B Hydrophobic odor molecules enter the aqueous sensillum lumen via pores penetrating the cuticular hair wall. Hydrophilic OBPs are proposed to bind and transport odors to receptor proteins located in the neuronal membranes. ODEs (pathway I) in the sensellum lumen are proposed to degrade these odor molecules. Cytoplasm of support cells contain xenobiotic inactivating enzymes, such as glutathione-S-transferase (GST) (pathway I la) which may also serve to inactivate odor molecules (pathway lib). Interactions between OBPs and ORs and the function of SNMP are unclear. Modified from Rogers et al. (1999).

How the body s defenses respond to foreign compounds, especially the defenses provided by the biochemical pathways of xenobiotic metabolism... 

Fig. 11 Biochemical pathways for the formation, detoxification, and cellular effects of xenobiotic free radical intermediates and reactive oxygen species (ROS). Fe iron, G-6-P glucose-6-phos-phate, GSH glutathione, GSSG glutathione disulfide, H2O2 hydrogen peroxide, FIO hydroxyl radical, LPO lipoxygenase, NADP nicotinamide adenine dinucleotide phosphate, O2 superoxide, P450 cytochromes P450, PHS prostaglandin H synthase, SOD superoxide dismutase. (Modified from Wells et al. 1997)...

Lewinska M, Zmrzljak UP, Rozman D (2013) Low nucleotide variability of CYP51A1 in humans meta-analysis of cholesterol and bile acid syn- 2759. thesis and xenobiotic metabolism pathways. Acta Chim Slovenica 60 875-883 Lamb DC, Kaderbhai NN, Venkateswarlu K, Kelly DE, Kelly SL, Kaderbhai MA (2001) Human sterol 14a-demethylase activity is enhanced by the membrane-bound state of cytochrome b. Arch 2760. Biochem Biophys 395 78-84 Lamb DC, Kelly DE, Kelly SL (1998) Molecular diversity of sterol 14a-demethylase substrates in plants, fungi and humans. EEBS Lett 425 263-265 Strushkevich N, Usanov SA, Park HW (2010) 2761. 

Moorhouse KG, Logan CJ, Hutson DH, Dodds PF (1990) The incorporation of 3-phenoxybenzoic acid and other xenobiotics acids into xenobiotic lipids by enzymes of the monoacylglycerol pathway in microsomes from adult and neonatal tissues. Biochem Pharmacol 39 1529-1536... 

Porphyria may result from several different enzyme deficiences in the porphyrin biosynthetic pathway. The condition is often hereditary but may be induced by drugs or other xenobiotic substances and may be continuous or intermittent.425 426 429 In one type of congenital porphyria uroporphyrin I is excreted in large quantities. The biochemical defect appears to be a deficiency of the cosynthase that is required for formation of protoporphyrin IX. Another type of porphyria results from overproduction in the liver of... 

Biochemical and molecular toxicology consider events at the biochemical and molecular levels, including enzymes that metabolize xenobiotics, generation of reactive intermediates, interaction of xenobiotics or their metabolites with macromolecules, gene expression in metabolism and modes of action, and signaling pathways in toxic action. 

Figure 7.1 Pathways of xenobiotic species prior to their undergoing any biochemical interactions that could lead to toxic effects.

Metabolic pathways such as the electron transport chain of mitochondrial respiration and biochemical reduction of oxygen by enzymes of xenobiotic metabolism,... 

Conjugates of xenobiotics eliminated in the urine and feces of exposed animals normally provide the basis upon which secondary metabolic pathways are proposed. In many cases, the mechanism of formation of the conjugate is readily apparent. Such is the case with phenols which are excreted as sulfate and glucuronide conjugates. The biochemical donors are known, the enzymes are well characterized and the substrate specificities of these enzymes are generally well established. Although this does not rule out the... 

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