Metabolites, high concentration

Investigations into the fate of surfactants under different discharge conditions have demonstrated the importance of wastewater treatment in reducing the amounts of residues entering the natural aquatic environment, but also highlight the need for sophisticated and reliable analytical methods in order to obtain monitoring data of both the parent surfactants as well as the quite often more highly concentrated metabolites. 

The range of concentrations relevant for clinical diagnosis is spread over more than 8 decades from high concentrated metabolites, like glucose, serum proteins and therapeutic drugs down to the concentration of hormones. 

Compounds Causing Cardiovascular Toxicity Alcohols are the most important compounds causing vascular toxicity. Ethanol depresses cardiac muscle and attenuates its contractivity when the concentration of ethanol in the blood exceeds 0.75 mg/100 mL. Ethanol also causes arrhythmias, and a metabolite of ethanol, acetaldehyde, also depresses the heart. Furthermore, high concentrations of acetaldehyde cause cardiac arrhythmias. The cardiovascular toxicity of methanol is about the same as that of ethanol, whereas al cohols with longer chains are more toxic than ethanol. 

Through all these calculations of the effect of pH and metal ions on the ATP hydrolysis equilibrium, we have assumed standard conditions with respect to concentrations of all species except for protons. The levels of ATP, ADP, and other high-energy metabolites never even begin to approach the standard state of 1 M. In most cells, the concentrations of these species are more typically 1 to 5 mM or even less. Earlier, we described the effect of concentration on equilibrium constants and free energies in the form of Equation (3.12). For the present case, we can rewrite this as... 

All of the compounds we shall study in this Chapter are primary metabolites though both phases of growth will be studied. For example, as we shall see, citric add is produced continuously at low levels during trophophase but only accumulates at high concentration during idiophase. 

Administration of dibutyltin dichloride intraperito-neally to rats led to the formation of butyl(3-hydroxy-butyl)tm, butyl(4-hydroxybutyl)tin, and monobutyltin. The major metabolite (buty 1(3-hydroxybutyl)tin) was distributed to the kidney at a relatively high concentration compared with the other metabolites, and its concentration increased with time. Butyl(4-hydroxybutyl)tin was found in urine only. The parent compound and other metabolites were detected in the brain (Ishizaka et al., 1989). Dibutyltin diacetate was destarmylated by 14% within 90 h following a single oral dose in mice at 1.1 mg/kg body weight, with several butyltin derivatives found in the liver or faeces (Boyer, 1989). 

High concentrations of endosulfan sulfate were found primarily in the liver, intestine, and visceral fat 24 hours after mice were exposed to a single dose of -endosulfan (Deema et al. 1966). Five days following a single oral administration of " C-endosulfan to rats, the diol, sulfate, lactone, and ether metabolites were detected in the feces (Borough et al. 1978). In sheep, endosulfan sulfate was detected in the feces, and endosulfan alcohol and a-hydroxyether were detected in the urine (Gorbach et al. 1968). 

Many of the components of PCB and PBB mixtures are both lipophilic and stable, chemically and biochemically. Similar to the persistent organochlorine insecticides and their stable metabolites, they can undergo strong bioconcentration and bioaccumulation to reach relatively high concentrations in predators. 

Animal studies indicate that trichloroethylene can sensitize the heart to epinephrine-induced arrhythmias. Other chemicals can affect these epinephrine-induced cardiac arrhythmias in animals exposed to trichloroethylene. Phenobarbital treatment, which increases the metabolism of trichloroethylene, has been shown to reduce the trichloroethylene-epinephrine-induced arrhythmias in rabbits (White and Carlson 1979), whereas high concentrations of ethanol, which inhibits trichloroethylene metabolism, have been found to potentiate trichloroethylene-epinephrine-induced arrhythmias in rabbits (White and Carlson 1981). These results indicate that trichloroethylene itself and not a metabolite is responsible for the epinephrine-induced arrhythmias. In addition, caffeine has also been found to increase the incidence of epinephrine-induced arrhythmias in rabbits exposed to trichloroethylene (White and Carlson 1982). 

The tolerance of the strains to high concentrations of pentachlorophenol—S. chlorophenolica appears to be less sensitive than M. chlorophenolicus (Miethling and Karlson 1996). This may be attribnted to the ability of the cells to adapt their metabolism to avoid synthesis of toxic concentrations of chlorinated hydroquinones, and is consistent with the low levels of these metabolites measnred in the cytoplasm of cells metabolizing pentachlorophenol (McCarthy et al. 1997). Inocnla have also been immobilized on polyurethane that, in addition, ameliorates the toxicity of chlorophenols (Valo et al. 1990). 

Fat tissues do not appear to highly concentrate diisopropyl methylphosphonate or its metabolites. Tissue blood ratios for adipose deposits range from 1.3 to 3.6 in the species studied (Hart 1976). There was a surprisingly high concentration of radiolabel in the skin for mice with a tissue blood ratio of 14.6 (Hart 1976). It has been suggested, however, that the skin samples were contaminated with urine. 

Among common in vitro metabolizing systems, liver microsomes and liver S9 fractions are used more often in metabolite synthesis than other systems. The majority of drug metabolism is mediated by CYPs [8]. Liver microsomes contain a high concentration of CYPs and other... 

Another phenomenon which is difficult to interpret on the ketolysis basis is the finding that the rate of utilization of the ketones rises sharply with increased concentrations in the blood and tissues. The quantities oxidized under such circumstances apparently have no relationship to the carbohydrate utilized. In fact, they may practically exclude the oxidation of other metabolites since they have been reported to account for 90% of the total oxygen consumption at sufficiently high concentrations. However, such levels of ketones are never found normally and possibly a different relationship to carbohydrate occurs at physiological values. Likewise it is not clear whether a similar response would be expected if the natural isomer alone were administered. 

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