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Biodegradation of Xenobiotic CompoundsBY: Lakshmi K Sugavanam | Category: Others | Submitted: 2011-04-07 20:36:32
Article Summary: "Role of hepatic enzymes and oxygenases in the degradation of xenobiotic compounds. Xenobiotic compounds are those that are found in living systems or in the environment that are not natural to them. Substances that are present in abnormally high concentrations can also be considered xenobiotic..."
Biodegradation of Xenobiotic compounds
Xenobiotic compounds are those that are found in living systems or in the environment that are not natural to them. Substances that are present in abnormally high concentrations can also be considered xenobiotic. For example, the antibiotic drugs found in the human body are considered as xenobiotics as they are neither produced by the human body itself nor a normal part of the diet. The term xenobiotic is derived from Greek where xenos means foreign or strange and bios means life. Even a natural substance can be considered a xenobiotic if it has entered the body of another organism. But, this term is generally used to denote a chemical or a pollutant that is foreign to almost all living organisms.
Biodegradation is the complete breakdown of the complex and toxic contaminants to non-toxic, simple elements by the action of microbes. Hence, these contaminants act as the microbial food substrate. Biodegradation, in general, can be considered as a series of steps of biological degradation (or pathway) that ultimately result in the oxidation of the compound which most often results in the generation of energy. Xenobiotics in the body are removed by a process called xenobiotic metabolism. In this process, these compounds are degraded by the liver where the enzymes like cytochrome P450 activate the xenobiotics by the process of oxidation, hydrolysis, reduction or hydration and then, this activated compound conjugates with glucuronic acid, sulphuric acid or glutathione. These are then excreted out of the body by the usual excretion routes of urination, exhalation, sweating and excretion.
Xenobiotics in the environment are degraded by the microbes. Microbes have the capacity to degrade all naturally occurring compounds; this is called the principle of microbial infallibility. It was proposed by Alexander in 1965. Microbes can degrade many of the xenobiotic compounds, but not all. The compounds that resist biodegradation and persist in the environment are called 'recalcitrant'.
For complete biodegradation, oxidation of parent compound occurs to form carbon dioxide and water. Each step in the degradation pathway is catalyzed by a specific enzyme produced by the degrading cell. Degradation of some xenobiotics depends on the presence of a specific compound, which induces the required enzymes. These enzymes are metabolized to provide both energy and reducing equivalents for the degradation of xenobiotic compounds.
Degradation on xenobiotics requires the action of enzymes like oxygenases. They are a group of enzymes that change the hydrophobic nature of the organic compound to water-soluble. And this water-soluble compound can be broken down by a larger number of other microorganisms. Two main classes of oxygenases are known. These are monooxygenases and dioxygenases. These enzymes participate in the oxidative metabolism of a wide variety of chemicals of pharmaceutical, agricultural and environmental significance. Some of the most widely recognized substrates for this class of enzymes are the aliphatic and aromatic hydrocarbons of both endobiotic and xenobiotic sources.
Monoxygenases are a class of enzymes that insert one atom of the oxygen molecule into the substrate; the other atom becomes reduced to water. They are also more complex and can catalyze several different types of Oxygen atom insertion reactions. Since monoxygenases can oxidize two substrates, they are also called mixed function oxidizers. Also, since one of the main substrates gets hydroxylated, they are also called hydroxylases.
The general stoichiometry of the reaction is as follows:
R-H + NAD (P) H +O2 -----> R-OH + NAD (P) + H2O
Dioxygenases incorporate both atoms of the oxygen molecule into the substrates. Dioxygenases are crucial in initiating the decomposition of a variety of chlorinated and nitro-aromatic compounds as well as non-substituted polycyclic aromatic hydrocarbons. Many of these compounds are first degraded to catechol or protocatechuate by oxygenases (both dioxygenases and monooxygenases). The intermediates are metabolized by ring-cleavage type of dioxygenases to either beta-ketoadipate or 2-keto-4-hydroxyvalerate. These intermediates then enter the TCA cycle.
When the organism evolves to start tolerating the xenobiotic compound, it can lead to the phenomenon called resistance. An example is the resistance of the body to certain antibiotics. Also, some of these substances are resistant to degradation, for example, plastics and certain pesticides. However, it is understood that microbes have the ability to degrade almost any of these recalcitrant compounds.
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