ECOLOGICAL BIOCHEMISTRY - Study Guide - V. M. Isaenko 2005

Chapter 10. BIOTRANSFORMATION OF XENOBIOTICS

Chemical substances of anthropogenic and natural origin, upon entering an ecosystem, undergo METABOLISM, accumulate, or are excreted.

For a Cell, it matters little whether foreign substances originate from another Organism or from the anthropogenic environment. Evidently, organisms possess a biochemical defense system designed to detoxify or mitigate the effects of a vast array of chemically diverse compounds. This explains the remarkable capacity of organisms to metabolize complex man-made substances.

Within ecosystems, chemical substances are exposed to various environmental factors. During their persistence in the external environment, they are acted upon by a complex of biotic and abiotic factors that drive chemical transformation, inactivation, or, conversely, activation. Upon entering Cells, most of these substances undergo enzymatic biotransformation. This process proves beneficial only when the resulting products are no less safe—or less toxic—than the parent compounds.

The metabolism of foreign chemical compounds known as xenobiotics (from the Greek xenos — foreign, bios — life) serves as a unique chemical defense mechanism for organisms. It also regulates the action of biologically active compounds within the body. As previously noted, the transformation of certain xenobiotics can sometimes yield even more toxic substances. Therefore, the term "biotransformation" rather than "detoxification" more accurately reflects the true nature of xenobiotic metabolism in living organisms.

BIOTRANSFORMATION OF XENOBIOTICS within the body is one of the most critical factors determining their biological activity. Various Organs and Tissues participate in this process, including the Liver, Kidneys, Lungs, intestines, Spleen, Adrenal Glands, Skin, Mammary Glands, and immune system cells. The liver exhibits the highest metabolic activity regarding xenobiotics, which underpins its primary physiological Functions: barrier, detoxification, and excretory. The liver plays an especially vital role in xenobiotic biotransformation when they enter

via the digestive tract. In this case, exogenous chemical compounds are absorbed by the mucosa of The Stomach and Small Intestine and are subsequently transported via the bloodstream directly to the liver.

The principal enzyme systems responsible for xenobiotic biotransformation are localized within polygonal liver cells, known as hepatocytes. These enzyme systems are closely associated with The Endoplasmic reticulum, particularly its smooth (agranular) regions.

Upon the disruption of the tubular and vesicular structures of the endoplasmic reticulum, vesicular membrane fragments known as microsomes are formed. Their primary enzymatic systems include oxidoreductases, transferases, and esterases.

In addition to microsomes, xenobiotic biotransformation is also catalyzed by a range of Enzymes with non-microsomal localization. For instance, Mitochondria contain amine oxidases that convert amines into aldehydes, as well as enzymes that aromatize saturated alicyclic compounds into benzoic derivatives. Furthermore, enzymes catalyzing The oxidation of alcohols and aldehydes—such as aldehyde oxidase and xanthine oxidase—have been identified. Blood Plasma also contains amine oxidases and esterases capable of metabolizing xenobiotics.

It should be noted that there remain numerous metabolic transformations of xenobiotics whose specific enzymes and cellular localizations have yet to be determined.