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SECTION 12. INACTIVATION OF FOREIGN COMPOUNDS IN THE BODY

Main subjects:

12.1. System of microsomal oxidation of compounds and conjugation reactions

12.2. Detoxification of waste products of intestinal microflora

12.3. Biotransformation of drugs in the liver

12.4. Main mechanisms of phagocytosis

The foreign compounds coming into the body from the gastro-intestinal tract, via skin and lungs and not used for plastic and energetic purposes are referred to as xenobiotics. They are medicines, dyes, pesticides, and metabolic products of intestinal microflora. Hydrophilic xenobiotics are excreted in the urine from the body, but hydrophobic compounds can be accumulated and, interacting with proteins and lipids of cell, damage their structure and impair the functions. There is a number of protective mechanisms in the body ensuring detoxification of foreign and toxic compounds that invade the body. Detoxification of xenobiotics occurs in many tissues, but most actively in the liver. The process may consist of one or two steps. The first stage provides the increase of hydrophilicity of foreign compounds and includes hydrolytic, oxidation, hydroxylation, and reduction reactions; the second stage consists in the conjugation of compounds unchanged or chemically modified at the first stage with some metabolites.

However, it should be noted that some polar xenobiotics are excreted in an invariable form.

Phagocytosis, which is one of the most important mechanisms of immunity, plays a major role in the defense of the organism against invading microorganisms.

12.1. SYSTEM OF MICROSOMAL

OXIDATION OF COMPOUNDS AND CONJUGATION REACTIONS

The first stage of the inactivation of the most xeno-biotics begins with the reaction of their oxidation by enzymes of the smooth endoplasmic reticulum of the liver cells. When isolated from cells, the fragments of these membranes form microsomes. Therefore, the oxidation of substrates with the participation of the electron transport system localized in the membranes of endoplasmic reticulum is referred to as microsomal oxidation. There are two electron transport systems of oxidation in the liver which catalyze the hydroxylation of the substrates (Fig. 12.1), and they are monooxygen-eses.

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