Compounds and Xenobiotics

The reactivity of both endogenous compounds and xenobiotics with CYP is fairly broad, and is governed by a complex combination of physiochemical and structural properties [5]. A comprehensive review of this enzyme system and its critical role in the mechanisms of toxicity for many important chemicals is beyond the scope of this chapter, and the reader is directed to reviews on the topic [6-10]. 

In aquatic environments, reactions are, in many situations, driven by DOC and their interactions with natural compounds and xenobiotics. The more intensive use of spectroscopic tools could help in making headway toward understanding the fate of metals, pesticides, and other xenobiotics in the environment. 

It has been suggested that multidrug resistance proteins (MRPs) play an important role in the transport and detoxification of a wide range of endogenous compounds and xenobiotics. They are predominantly expressed at the apical membrane of the small intestine, proximal tubules of the kidney and canalicular membrane of hepatocytes involved in intestinal, renal and hepatobiliary excretion of compounds. 

One of the many families included in the MFS is the SLC (solute carrier) superfamiiy. The SLC superfamiiy represents approximately 300 genes in the human genome that encode for either facilitated transporters or secondary active symporters or antiporters. Members of the SLC superfamiiy transport various ionic and nonionic endogenous compounds and xenobiotics. The SLC22 family includes anion and cation transporters (Organic Anion Transporters, OATs Organic Cation Transporters, OCTs). 

SLC TRANSPORTERS The SLC superfamily includes 43 families and contains 300 human genes. Many of these genes are associated with genetic diseases (Table 2-2). SLC transporters transport diverse ionic and nonionic endogenous compounds and xenobiotics, acting either as facilitated transporters or as secondary active symporters or antiporters. 

The anaerobic digestion process can be inhibited by substances in the waste that are toxic to anaerobic microorganisms. The common inhibitors include ammonia, sulphide, long-chain fatty acids, salts, heavy metals, phenolic compounds and xenobiot-ics (Chen, Cheng, Creamer, 2008 Mata-Alvarez, 2003). 

Abnormal elevation of HO activity in response to metals and other xenobiotics has both negative and positive consequences for cells. While the physiological role of HO involves the turnover of heme compounds, a protracted increase in the de novo synthesis of HO has been generally associated with perturbation of cellular processes which may lead to cell injury or death. Reduction of heme via HO can deplete cytochrome P-450 levels, inhibit mixed function oxidase activities, and deplete mitochondrial respiratory cytochromes (Maines and Kappas 1977). Cellular respiration and biotransformation of endogenous compounds and xenobiotics may become compromised. 

Human exposure to environmental contaminants has been investigated through the analysis of adipose tissue, breast milk, blood and the monitoring of faecal and urinary excretion levels. However, while levels of persistent contaminants in human milk, for example, are extensively monitored, very little is known about foetal exposure to xenobiotics because the concentrations of persistent compounds in blood and trans-placental transmission are less well studied. Also, more information is needed in general about the behaviour of endocrine disruptive compounds (and their metabolites) in vivo, for example the way they bind to blood plasma proteins. 

Cellular defense mechanisms against toxins (A multistep mechanism for elimination of toxic metabolites and xenobiotics. It involves various transport, oxidation, and conjugation steps.) are usually divided into several steps as it is visualized on Fig. 3. Organic anion transporting proteins (OATPs) are responsible for the cellular uptake of endogenous compounds and... 

Two important examples of reductive metabolism of xenobiotics are the reductive dehalogenation of organohalogen compounds, and the reduction of nitroaromatic compounds. Examples of each are shown in Figure 2.13. Both types of reaction can take place in hepatic microsomal preparations at low oxygen tensions. Cytochrome P450 can catalyze both types of reduction. If a substrate is bound to P450 in the... 

---