Xenobiotic molecules

The classification of P450s, which is based on amino acid sequencing, bears some relationship to metabolic function. That said, some xenobiotic molecules, especially... 

Table 12 shows redox properties of some redox systems of biochemical nature. Generally, the redox potentials are modest, cytochrome P450 possibly being an exception. If cytochrome P450 functions as an electron transfer oxidant towards xenobiotic molecules, it is necessary to postulate a considerably higher potential (1.3-1.8V) from considerations of the Marcus theory (Eberson, 1990). 

Serum albumin is the most abundant protein in blood plasma. Its primary function is to control the colloidal osmotic pressure in blood, but is also important for its buffering capacity and for its ability to transport fatty acids and bilirubin, as well as xenobiotic molecules. The physiological implications of its esterase-like activity are unknown (see Sect. 3.7.5). 

N-dealkylation results from an alkyl substitution on an aromatic molecule, which is one of the first places where microorganisms initiate catabolic transformation of atrazine, a xenobiotic molecule (Fig. 15.2). It is a typical example of a reaction leading to transformation of pesticides like phenyl ureas, acylanihdes, carbamates, s-tri-azines, and dinitranilines. The enzyme mediating the reaction is a mixed-function oxidase, requiring a reduced nicotinamide nucleotide as an H donor. 

Oxirene (113) and oxirane (114), oxetene (115) and oxetane (116), the heterocyclic analogues of cyclopropane and cyclobutane respectively, are rarely encountered in xenobiotic molecules. With the exception of oxirane derivatives, which are formed as... 

On the other hand, the presence of quickly mineralized substrates in higher concentrations may facilitate an initial transformation of the xenobiotic molecule by co-metabolism. The co-metabolized substance may then be available for further degradation and mineralization. Thus, the presence of other substrates may increase the possibilities for a substance to be degraded. 

Rich in both phase I (principally the cytochromes P450, catalyzing hydrolysis, reduction, and oxidation reactions) and phase II (catalyzing conjugation of xenobiotic molecules with hydrophilic moieties) biotransforming enzymes, the liver is the metabolic center of the body. In fact, most of the field of biochemistry is concerned with its metabolic reactions. The liver essentially converts ingested food into a balanced cell culture medium via metabolic interconversion of amino acids, carbohydrates, and lipids and synthesizes many substances that are subsequently exported for use in other areas of... 

Xenobiotic molecules with electrophilic centers are potential substrates for conjugation with the thiol groip of the tripeptlde... 

Olefinic bonds in xenobiotic molecules can also be targets of cytochrome P450-catalyzed epoxidation (Figure 32.5b). In contrast to arene oxides, the resulting epoxides are fairly stable and can be isolated and characterized. But like arene oxides, they are substrates of epoxide hydrolase to yield dihydrodiols. This is exempUlied by carbamazepine, whose 10,11-epoxide is a major and pharmacologically active metabolite in humans, and is further metabolized to the inactive dihydrodiol. ... 

There may exist intrinsic limitations to transport into cells due to steric effects or the mere size and shape of the xenobiotic molecule. 

Olefinic bonds in xenobiotic molecules can also be targets of cytochrome P450-catalyzed epoxidation (reaction 2-A). In contrast to arene oxides, the resulting epoxides are fairly... 

A chapter in an earlier compilation [1] bringing together fundamentals and applications of radiation chemistry illustrated applications to biochemistry and radiobiology. That chapter mainly described studies of redox processes in proteins and biomolecules. It therefore seemed appropriate to focus instead a major part of the present review on free radicals derived from xenobiotic molecules, especially drugs of interest in cancer therapy. 

Phase I reactions, which often create anchor points in the xenobiotic molecule for subsequent conjugation, comprise oxidations (electron removal, dehydrogenation and hydroxylation), reductions (electron donation, hydrogenation and removal of oxygen), and hydrolytic reactions. Many metabolic reactions take place in the endoplasmic reticulum of the liver cells. Other organs, particularly kidneys and lungs, also participate in drug metabolism. In addition, a variety of other tissues (brain, skin, intestinal mucosa) have the capacity to metabolize xenobiotics. 

Taken from Khan et al. (1974), Gibson and Skett (1986) and James (1987). R = rest of organic xenobiotic molecule. 

LC-MS techniques have been shown to be very useful for the direct analysis of glucuronide conjugates of xenobiotic molecules in biological fluids, as well as in in vitro... 

A polar xenobiotic molecule will not enter the fatty tissue but will be absorbed by the liver via the blood-hver (B-L) equilibrium. The function of the liver is to metabolize the xenobiotic molecule, probably to a more polar molecule, for eventual excretion in the urine and feces. 

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