Xenobiotics: What are they? Role in Metabolism and Xenobiotic Substances in the Environment

From the Greek “xenos” which means “strange”, they are chemical compounds foreign to an organism or biological system.

It can be found in an organism but is not usually produced or expected to exist in that organism. The term also applies to substances present in concentrations much higher than the normal level.

In particular, drugs such as antibiotics are xenobiotic in humans because they are not produced by the human body and they are not part of the human diet. Pollutants such as dioxins and PCBs are xenobiotic, studying their effect on biota. Certain natural compounds can be considered xenobiotic if they are assimilated by another organism.

Xenobiotics can be grouped as carcinogens, drugs, environmental pollutants, food additives, hydrocarbons, and pesticides.

Function in metabolism

The body removes xenobiotics by xenobiotic metabolism. This consists of the deactivation and excretion of xenobiotics, and occurs mainly in the liver. The routes of excretion are urine, feces, breath and sweat.

Liver enzymes are responsible for the metabolism of xenobiotics by first activating them (oxidation, reduction, hydrolysis and / or hydration of the xenobiotic) and then conjugating the active secondary metabolite with glucuronic acid, sulfuric acid or glutathione, followed by excretion in the bile or urine.

An example of a group of enzymes involved in xenobiotic metabolism is the hepatic microsomal cytochrome P450. These enzymes that metabolize xenobiotics are very important for the pharmaceutical industry, as they are responsible for the breakdown of drugs.

Although the body can eliminate xenobiotics by reducing it to a less toxic form through xenobiotic metabolism and then excreting it, it is also possible that it becomes a more toxic form in some cases. This process is called bioactivation and can lead to structural and functional changes in the microbiota.

Exposure to xenobiotics can alter the structure of the microbiome community, either increasing or decreasing the size of certain bacterial populations depending on the substance.

The resulting functional changes vary by substance and may include increased expression in genes involved in stress response and antibiotic resistance, changes in the levels of metabolites produced, etc.

Organisms can also evolve to tolerate xenobiotics. An example is the coevolution of tetrodotoxin production in the rough-skinned newt and the evolution of resistance to tetrodotoxin in its predator, the common garter snake.

In this predator-prey pair, an evolutionary arms race has produced high levels of toxin in the newt and correspondingly high levels of resistance in the snake. This evolutionary response is based on the evolution of the modified forms of the ion channels on which the toxin acts, thus becoming resistant to its effects.

Another example of a xenobiotic tolerance mechanism is the use of ATP-binding cassette transporters, which is largely exhibited in insects. These transporters contribute to resistance by allowing the transport of toxins through the cell membrane, thus preventing the accumulation of these substances within cells.

Xenobiotics in the environment

Xenobiotic substances are a problem for wastewater treatment systems, as they are many in number, and each will present its own problems on how to eliminate them.

Some xenobiotics are resistant to degradation. Xenobiotics such as polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and trichlorethylene (TCE) accumulate in the environment due to their recalcitrant properties and have become an environmental problem due to their toxicity and accumulation.

This occurs particularly in the subsurface environment and water sources, as well as in biological systems, which have the potential to affect human health.

Some of the main sources of pollution and introduction of xenobiotics into the environment come from large industries, such as pharmaceuticals, fossil fuels, pulp and paper bleaching, and agriculture.

For example, they can be organochlorine synthetics such as plastics and pesticides, or natural organic chemicals such as polyaromatic hydrocarbons (HPA) and some fractions of crude oil and coal.

Microorganisms can be a viable solution to the problem of environmental contamination through the production of xenobiotics; a process known as bioremediation.

Microorganisms are capable of adapting to xenobiotics introduced into the environment through horizontal gene transfer, in order to make use of these compounds as energy sources.

This process can be further altered to manipulate the metabolic pathways of microorganisms in order to degrade harmful xenobiotics under specific environmental conditions at a more desirable rate.

Bioremediation mechanisms include both genetically engineered microorganisms and the isolation of naturally occurring xenobiotic-degrading microbes.

Research has been done to identify the genes responsible for the ability of microorganisms to metabolize certain xenobiotics and it has been suggested that this research can be used to engineer microorganisms specifically for this purpose.

Xenobiotics can be limited in the environment and difficult to access in areas such as the subsurface environment. The degrading organisms can be designed to increase mobility in order to access these compounds, including enhanced chemotaxis.

A limitation of the bioremediation process is that optimal conditions are required for the correct metabolic functioning of certain microorganisms, which can be difficult to find in an environmental setting.

In some cases, a single microorganism may not be able to carry out all the metabolic processes necessary for the degradation of a xenobiotic compound and, therefore, “syntrophic bacterial consortia” can be used.

In this case, a group of bacteria works together, causing the end products of one organism to be broken down by another organism. In other cases, the products of one microorganism can inhibit the activity of another and therefore a balance must be maintained.

Many xenobiotics produce a variety of biological effects, which are used when characterized by the use of bioassays.

Before they can be registered for sale in most countries, xenobiotic pesticides must undergo a comprehensive assessment for risk factors, such as toxicity to humans, ecotoxicity, or persistence in the environment.

For example, during the registration process, it was found that the herbicide, chloradulam-methyl, degraded relatively quickly in soil.