Violation of the amount of protein synthesized. Antibiotics that inhibit protein synthesis on ribosomes

Among the causes of protein synthesis disorders, various types occupy an important place. nutritional deficiency(complete, incomplete fasting, lack of essential amino acids in food, violation of a certain quantitative ratio between essential amino acids entering the body).

If, for example, tryptophan, lysine, and valine are contained in tissue protein in equal ratios (1:1:1), and these amino acids are supplied with food protein in a ratio of 1:1:0.5, then tissue protein synthesis will be ensured evenly half. The absence of at least one (out of 20) essential amino acids in cells stops protein synthesis as a whole.

An impairment in the rate of protein synthesis may be due to a disorder in the function of the corresponding genetic structures. Damage to the genetic apparatus can be either hereditary or acquired, arising under the influence of various mutagenic factors (ionizing radiation, ultra-violet rays etc.). Some antibiotics cause disruption of protein synthesis. So, “errors” in reading genetic code may occur under the influence of streptomycin, neomycin and other antibiotics. Tetracyclines inhibit the addition of new amino acids to a growing polypeptide chain (the formation of strong covalent bonds between its chains), preventing the splitting of DNA strands.

One of the important reasons causing disruption of protein synthesis may be dysregulation of this process. Regulation of the intensity and direction of protein metabolism is controlled by the nervous and endocrine systems, the effects of which are realized by influencing various enzyme systems. Decebration of animals leads to a decrease in

protein synthesis. Growth hormone, sex hormones and insulin under certain conditions stimulate protein synthesis. Finally, the cause of its pathology may be a change in the activity of cell enzyme systems involved in protein synthesis.

The result of these factors is a decrease in the rate of synthesis of individual proteins.

Quantitative changes in protein synthesis can lead to changes in the ratio of individual protein fractions in the blood serum - dysproteinemia. There are two forms of dysproteinemia: hyperproteinemia (increased content of all or individual types of proteins) and hypoproteinemia (decreased content of all or individual proteins). Thus, some diseases of the liver (cirrhosis, hepatitis), kidneys (nephritis, nephrosis) are accompanied by a decrease in albumin synthesis and a decrease in its content in the serum. A number of infectious diseases accompanied by extensive inflammatory processes lead to an increase in synthesis and a subsequent increase in the content of gamma globulins in the serum. The development of dysproteinemia is usually accompanied by shifts in homeostasis (impaired oncotic pressure, water balance). A significant decrease in the synthesis of proteins, especially albumins and gamma globulins, leads to a sharp decrease in the body's resistance to infection.

With damage to the liver and kidneys, some acute and chronic inflammatory processes (rheumatism, infectious myocarditis, pneumonia), qualitative changes occur in protein synthesis, and special proteins with altered properties are synthesized, for example, C-reactive protein. Examples of diseases caused by the presence of pathological proteins are diseases associated with the presence of pathological hemoglobin (hemoglobinosis), blood clotting disorders with the appearance of pathological fibrinogens. Unusual blood proteins include cryoglobulins, which can precipitate at temperatures below 37 ° C (systemic diseases, cirrhosis of the liver).

Hydrolysis and absorption of food proteins in the gastrointestinal tract.

Disturbance of the first stage of protein metabolism

In the stomach and intestines, hydrolytic breakdown of food proteins into peptides and amino acids occurs under the influence of enzymes from gastric juice (pepsin), pancreatic (trypsin, chymotrypsin, aminopeptidase and carboxypeptidase) and intestinal (aminopeptidase, dipeptidase) juices. Amino acids formed during the breakdown of proteins are absorbed by the wall of the small intestine into the blood and consumed by the cells of various organs. Disruption of these processes occurs in diseases of the stomach (inflammatory and ulcerative processes, tumors), pancreas (pancreatitis, blockage of ducts, cancer), small intestine (enteritis, diarrhea, atrophy). Extensive surgical interventions, such as removal of the stomach or a significant part of the small intestine, are accompanied by violation of the breakdown and absorption of food proteins. The absorption of food proteins is impaired during fever due to a decrease in the secretion of digestive enzymes.

With a decrease in the secretion of hydrochloric acid in the stomach, the swelling of proteins in the stomach and the conversion of pepsinogen to pepsin decrease. Due to the rapid evacuation of food from the stomach, proteins are not sufficiently hydrolyzed into peptides, i.e. Some proteins enter the duodenum unchanged. It also interferes with the hydrolysis of proteins in the intestine.

Insufficient absorption of food proteins is accompanied by a deficiency of amino acids and impaired synthesis of its own proteins. The lack of dietary proteins cannot be fully compensated by the excessive administration and absorption of any other substances, since proteins are the main source of nitrogen for the body.

Protein synthesis occurs in the body continuously throughout life, but occurs most intensively during the period of intrauterine development, in childhood and adolescence.

The causes of protein synthesis disorders are:

Lack of sufficient amino acids;

Energy deficiency in cells;

Disorders of neuroendocrine regulation;

Disruption of the processes of transcription or translation of information about the structure of a particular protein encoded in the cell genome.

The most common cause of protein synthesis disorder is lack of amino acids in the body due to:

1) digestive and absorption disorders;

2) low protein content in food;

3) nutrition with incomplete proteins, which lack or contain insignificant amounts of essential amino acids that are not synthesized in the body.

A complete set of essential amino acids is found in most animal proteins, while plant proteins may lack or contain some of them (for example, corn proteins are low in tryptophan). Flaw in the body at least one of essential amino acids leads to a decrease in the synthesis of one or another protein, even with an abundance of others. Essential amino acids include tryptophan, lysine, methionine, isoleucine, leucine, valine, phenylalanine, threonine, histidine, arginine.

Deficiency of essential amino acids in food less often leads to a decrease in protein synthesis, since they can be formed in the body from keto acids, which are products of the metabolism of carbohydrates, fats and proteins.

Lack of keto acids occurs with diabetes mellitus, disruption of the processes of deamination and transamination of amino acids (hypovitaminosis B 6).

Lack of energy sources occurs during hypoxia, the action of uncoupling factors, diabetes mellitus, hypovitaminosis B1, nicotinic acid deficiency, etc. Protein synthesis is an energy-dependent process.

Disorders of neuroendocrine regulation of protein synthesis and breakdown. The nervous system affects protein metabolism direct and indirect action. When nerve influences are lost, cell trophic disorder occurs. Tissue denervation causes: cessation of their stimulation due to disruption of the release of neurotransmitters; impaired secretion or action of comediators that provide regulation of receptor, membrane and metabolic processes; disruption of the release and action of trophogens.

The action of hormones can be anabolic(increasing protein synthesis) and catabolic(increasing protein breakdown in tissues).

Protein synthesis increases under the influence of:

Insulin (provides active transport of many amino acids into cells - especially valine, leucine, isoleucine; increases the rate of DNA transcription in the nucleus; stimulates ribosome assembly and translation; inhibits the use of amino acids in gluconeogenesis, enhances the mitotic activity of insulin-dependent tissues, increasing the synthesis of DNA and RNA);

Somatotropic hormone (GH; the growth effect is mediated by somatomedins produced under its influence in the liver). The main one is somatomedin C, which increases the rate of protein synthesis in all cells of the body. This stimulates the formation of cartilage and muscle tissue. Chondrocytes also have receptors for growth hormone itself, which proves its direct effect on cartilage and bone tissue;

Thyroid hormones in physiological doses: triiodothyronine, binding to receptors in the cell nucleus, acts on the genome and causes increased transcription and translation. As a result, protein synthesis is stimulated in all cells of the body. In addition, thyroid hormones stimulate the action of GH;

Sex hormones that have a growth hormone-dependent anabolic effect on protein synthesis; androgens stimulate the formation of proteins in the male genital organs, muscles, skeleton, skin and its derivatives, and to a lesser extent in the kidneys and brain; The action of estrogens is directed mainly to the mammary glands and female genital organs. It should be noted that the anabolic effect of sex hormones does not affect protein synthesis in the liver.

Protein breakdown increases under the influence of:

Thyroid hormones with increased production (hyperthyroidism);

Glucagon (reduces the absorption of amino acids and increases the breakdown of proteins in muscles; activates proteolysis in the liver, and also stimulates gluconeogenesis and ketogenesis from amino acids; inhibits the anabolic effect of growth hormone);

Catecholamines (promote the breakdown of muscle proteins with the mobilization of amino acids and their use by the liver);

Glucocorticoids (increase protein synthesis and nucleic acids in the liver and increase the breakdown of proteins in muscles, skin, bones, lymphoid and adipose tissue with the release of amino acids and their involvement in gluconeogenesis. In addition, they inhibit the transport of amino acids into muscle cells, reducing protein synthesis).

The anabolic effect of hormones is carried out mainly by activating certain genes and increasing the formation of various types of RNA (messenger, transport, ribosomal), which accelerates protein synthesis; the mechanism of the catabolic action of hormones is associated with an increase in the activity of tissue proteinases.

A long-term and significant decrease in protein synthesis leads to the development of dystrophic and atrophic disorders in various organs and tissues due to insufficient renewal of structural proteins. Regeneration processes slow down. In childhood, growth, physical and mental development are inhibited. The synthesis of various enzymes and hormones (GH, antidiuretic and thyroid hormones, insulin, etc.) decreases, which leads to endocrinopathies and disruption of other types of metabolism (carbohydrate, water-salt, basal). The content of proteins in the blood serum decreases due to a decrease in their synthesis in hepatocytes. The production of antibodies and other protective proteins decreases and, as a result, the immunological reactivity of the body decreases.

Causes and mechanism of disruption of the synthesis of individual proteins. In most cases, these disorders are hereditary. They are based on the absence in cells of messenger RNA (mRNA), a specific matrix for the synthesis of any particular protein, or a violation of its structure due to a change in the structure of the gene on which it is synthesized. Genetic disorders, for example, the replacement or loss of one nucleotide in a structural gene, lead to the synthesis of an altered protein, often devoid of biological activity.

The formation of abnormal proteins can be caused by deviations from the norm in the structure of mRNA, mutations of transfer RNA (tRNA), as a result of which an inappropriate amino acid is added to it, which will be included in the polypeptide chain during its assembly (for example, during the formation of hemoglobin).

Causes, mechanism and consequences of increased breakdown of tissue proteins. Along with synthesis in the cells of the body, protein degradation constantly occurs under the action of proteinases. The renewal of proteins per day in an adult is 1-2% of the total amount of protein in the body and is associated mainly with the degradation of muscle proteins, while 75-80% of the released amino acids are again used for synthesis.

Preferanskaya Nina Germanovna
Associate Professor, Department of Pharmacology, Faculty of Pharmacy, First Moscow State Medical University named after. THEM. Sechenov

Antibiotics have a mainly bacteriostatic effect, with the exception of aminoglycosides that have a bactericidal effect and drugs used in large doses. These medicines have a wide spectrum of antimicrobial action and are often used in clinical practice, they are especially indispensable in the specific treatment of such rare infections as bartonellosis, brucellosis, cryptosporidiosis, cystic fibrosis, toxoplasmosis, tularemia, tuberculosis, anthrax, cholera, plague, etc.

Part I. Macrolides

Macrolides are a class of antibiotics that contain in the molecule a macrocyclic lactone ring associated with carbohydrate residues of amino sugars. Depending on the number of carbon atoms making up the ring, 14-membered, 15-membered and 16-membered macrolides are distinguished. Of all existing antibiotics, macrolides have proven themselves to be highly effective and safest chemotherapeutic agents. Macrolides are divided into two groups: natural and semi-synthetic .

The antimicrobial effect of macrolides is due to a disruption of protein synthesis on the ribosomes of the microbial cell. Macrolides reversibly bind to various domains of the catalytic peptyl-transferase center of the 50S ribosomal subunit and inhibit the processes of translocation and transpeptidation of peptides, which leads to the cessation of protein molecule assembly and slows down the ability of microorganisms to divide and reproduce. Depending on the type of microorganism and the concentration of the drug, they have a dose-dependent effect, exhibiting a bacteriostatic effect, and in large doses and on some strains of microorganisms - a bactericidal effect. The antimicrobial spectrum of action is very close to the group of natural penicillins.

Macrolides have lipophilic properties, are quickly absorbed into the gastrointestinal tract, create high tissue and intracellular concentrations, distributed in many tissues and secretions, are poorly retained in extracellular fluids, and do not penetrate the BBB. Their effect manifests itself mainly at the reproduction stage. They are highly effective only against actively dividing microorganisms, therefore they have proven themselves in the treatment of the acute period of the disease and have little or no effect on sluggish processes.

They have increased activity against gram “+” cocci and intracellular pathogens (chlamydia, mycoplasmas, legionella), suppress the development of gram-negative cocci, diphtheria bacilli, pathogens of brucellosis, amoebic dysentery. On gram “-” microorganisms of the family Enterobacteriaceae P. aeruginosa and gram “-” anaerobes are resistant. Pseudomonas and Acinetobacter are naturally resistant to all macrolides. Resistance of microorganisms to this group of drugs is associated with changes in the structure of receptors on the 50S subunits of ribosomes, which leads to disruption of the binding of the antibiotic to ribosomes. In macrolides, lincosamides and fenicols, binding to the 50S ribosomal subunit occurs at different sites, which results in the absence of cross-resistance. A feature of the antimicrobial action of macrolides is their bacteriostatic effect against those forms of bacteria that are resistant to such widely used groups as penicillins, streptomycins, and tetracyclines.

Macrolides are used for lower respiratory tract infections, including atypical forms, exacerbation of chronic bronchitis and community-acquired pneumonia. They are prescribed for upper respiratory tract infections (sinusitis, otitis, pharyngitis, tonsillitis), infections of the oral cavity, soft tissues, skin, infected acne and urogenital infections. Indications for their use are the prevention and treatment of mycobacteriosis, the prevention of rheumatic fever, endocarditis, with the aim of eradicating H. pylori ( clarithromycin). The immunomodulatory properties of macrolides are used for panbronchonchiolitis ( clarithromycin, roxithromycin) and cystic fibrosis ( azithromycin).

Basic side effects when using macrolides - gastrointestinal disorders, the risk of which does not exceed 5-8%. In rare cases, allergic reactions develop 2-3% (skin rash, swelling of the face, neck, feet, anaphylactic shock), less commonly cholestatic hepatitis and pseudomembranous colitis. The smallest frequency of administration of macrolides, improved pharmacokinetic parameters do not require dose adjustment in case of renal failure and are well tolerated by patients. Most macrolides (especially erythromycin and clarithromycin) are potent inhibitors of cytochrome P-450 (CYP 3A 4, CYP3A5, CYP3A7, CYP 1A 2), therefore, their use disrupts biotransformation and increases the maximum concentration in the blood of co-administered drugs. This is especially important to consider when using Warfarin, Cyclosporine, Theophylline, Digoxin, Carbamazepine etc., which are metabolized in the liver. Their combined use can cause the most dangerous complications (heart rhythm disturbances, prolongation of the Q-T interval, development of limb ischemia and gangrene). Spiramycin and azithromycin are not subject to oxidation by cytochrome P-450. In the body, macrolides undergo enterohepatic recirculation, are excreted mainly with bile, and only 5-10% of the drug is excreted by the kidneys.

Erythromycin (Erythromycinum) is produced by soil actinomycetes (radiant fungi), from the cultural liquid of which it was isolated in 1952. It is well absorbed from the gastrointestinal tract. In the acidic environment of the stomach, it is partially destroyed, so erythromycin should be administered in tablets coated with an acid-resistant coating that dissolves only in the intestines. The drug easily penetrates various tissues, incl. crosses the placental barrier. It does not enter brain tissue under normal conditions. After a single oral dose, the maximum concentration in the blood is reached after 2 hours. Erythromycin has a bioavailability of 2-3 hours, so to maintain therapeutic levels in the blood it should be administered 4 times a day. Higher doses orally: single - 0.5 g, daily - 2 g. Excreted in feces and, partially, in urine. Erythromycin tablets are most widely used for the treatment of pneumonia, bronchitis of various etiologies, scarlet fever, tonsillitis, purulent otitis media, diphtheria, and wound infections. The drug is used for severe infectious diseases, for the treatment of whooping cough, diphtheria. For conjunctivitis in newborns, it is administered intravenously, a single dose is diluted in 250 ml of isotonic sodium chloride solution, administered slowly over an hour. In gastroparesis, erythromycin dose-dependently stimulates gastric motility, increases the amplitude of pyloric contractions and improves antral-duodenal coordination. Topically used in the form of an ointment and solution for external use for the treatment of purulent-inflammatory skin diseases, infected wounds, trophic ulcers, bedsores and burns of II-III degree. Resistance of microorganisms to erythromycin quickly develops; the drug is low-toxic and rarely causes side effects. Sometimes dyspeptic disorders (nausea, vomiting) and allergic reactions occur. Bioavailability is significantly reduced when taking erythromycin with or after meals, because food reduces the concentration of this antibiotic in the blood by more than 2 times. Available in tubular, coated. obol. 100 and 250 mg; eye ointment 10 g (in 1 g 10,000 units); ointment for external and local use 15 mg - 10 thousand units/g. Suppositories for children, 0.05 g and 0.1 g. Powder for injection, 0.05, 0.1 and 0.2 g, and granules for suspension, 0.125 g and 0.2 g in 5 ml bottles.

The importance of protein metabolism for the body is determined, first of all, by the fact that the basis of all its tissue elements is made up of proteins, which are continuously subject to renewal due to the processes of assimilation and dissimilation of their main parts - amino acids and their complexes. Therefore, protein metabolism disorders in various variants are components of the pathogenesis of all pathological processes without exception.

The role of proteins in the human body:

· structure of all tissues

growth and repair (recovery) in cells

· enzymes, genes, antibodies and hormones are protein products

influence on water balance through oncotic pressure

· participation in the regulation of acid-base balance

A general idea of ​​protein metabolism disorders can be obtained by studying the nitrogen balance of the body and the environment.

1. Positive nitrogen balance is a condition when less nitrogen is excreted from the body than is taken in from food. It is observed during the growth of the body, during pregnancy, after fasting, with excessive secretion of anabolic hormones (GH, androgens).

2. Negative nitrogen balance is a condition when more nitrogen is excreted from the body than is taken in from food. Develops with fasting, proteinuria, bleeding, excessive secretion of catabolic hormones (thyroxine, glucocorticoids).

Typical violations protein metabolism

1. Violations in the quantity and quality of protein entering the body

2. Impaired absorption and synthesis of proteins

3. Violation of interstitial amino acid metabolism

4. Violation of the protein composition of the blood

5. Violation of the final stages of protein metabolism

1. Violations in the quantity and quality of protein entering the body

A) One of the most common reasons disorders of protein metabolism is quantitative or high quality protein deficiency. This is due to the limited supply of exogenous proteins during fasting, the low biological value of food proteins, and a deficiency of essential amino acids.

Manifestations of protein deficiency:

negative nitrogen balance

slowdown in growth and development of the body

insufficiency of tissue regeneration processes

weight loss

Decreased appetite and protein absorption

Extreme manifestations of protein deficiency are kwashiorkor and nutritional marasmus.

Nutritional marasmus is a pathological condition that occurs as a result of prolonged complete starvation and is characterized by general exhaustion, metabolic disorders, muscle atrophy and dysfunction of most organs and systems of the body.

Kwashiorkor is a disease that affects children. early age, is caused by a qualitative and quantitative protein deficiency under the condition of a general caloric excess of food.

b)Excessive protein intake causes the following changes in the body:

positive nitrogen balance

dyspepsia

· dysbacteriosis

intestinal autoinfection, autointoxication

aversion to protein foods

2. Impaired absorption and synthesis of proteins

· disturbances in the breakdown of proteins in the stomach (gastritis with reduced secretory activity and low acidity, gastric resections, stomach tumors). Proteins are carriers of foreign antigenic information and must be broken down during digestion, losing their antigenicity, otherwise their incomplete breakdown will lead to food allergies.

· malabsorption in the intestine (acute and chronic pancreatitis, pancreatic tumors, duodenitis, enteritis, resection of the small intestine)

pathological mutations of regulatory and structural genes

Dysregulation of protein synthesis (change in the ratio of anabolic and catabolic hormones)

3. Violation of interstitial amino acid metabolism

1. Impaired transamination (formation of amino acids)

· deficiency of pyridoxine (vit. B 6)

· fasting

liver diseases

2. Impaired deamination (destruction of amino acids) causes hyperaminoacidemia ® aminoaciduria ® changes in the ratio of individual amino acids in the blood ® impaired protein synthesis.

· lack of pyridoxine, riboflavin (B 2), nicotinic acid

hypoxia

· fasting

3. Impaired decarboxylation (proceeds with the formation of CO 2 and biogenic amines) leads to the appearance of a large amount of biogenic amines in tissues and disruption of local blood circulation, increased vascular permeability and damage to the nervous system.

hypoxia

ischemia and tissue destruction

4. Violation of the protein composition of the blood

Hyperproteinemia – increase in plasma protein > 80 g/l

Consequences of hyperproteinemia: increased blood viscosity, changes in its rheological properties and impaired microcirculation.

Hypoproteinemia– decrease in protein in blood plasma< 60 г/л

· fasting

Impaired digestion and absorption of proteins

Impaired protein synthesis (liver damage)

loss of protein (blood loss, kidney damage, burns, inflammation)

increased protein breakdown (fever, tumors, catabolic hormones)

Consequences of hypoproteinemia:

· ¯ resistance and reactivity of the body

· disruption of the functions of all body systems, because the synthesis of enzymes, hormones, etc. is disrupted.

5. Violation of the final stages of protein metabolism. The pathophysiology of the final stages of protein metabolism includes the pathology of the processes of formation of nitrogenous products and their removal from the body. Residual blood nitrogen is the non-protein nitrogen remaining after the precipitation of proteins.

Normally 20-30 mg% composition:

· urea 50%

amino acids 25%

· other nitrogenous products 25%

Hyperazotemia – increase in residual nitrogen in the blood

The accumulation of residual nitrogen in the blood leads to intoxication of the entire body, primarily the central nervous system and the development of a coma.

There are also toxic effects associated with the direct effect of xenobiotics on microsomal monooxygenases. Typical here is the mechanism of the toxic effect of carbon tetrachloride, which dissolves in all membrane elements of liver cells with a predominant accumulation in the microsomal fraction. Here it binds to cytochrome P-450, and a rapidly occurring reduction reaction leads to the formation of the CCl3 radical, which is the trigger in the mechanism of the damaging effect of this xenobiotic.

The radical stimulates sharply lipid peroxidation, causing damage to biomembranes and leads to the destruction of cytochrome P-450. As a result, these mechanisms, coupled with other, less significant ones, cause cell death. For the mechanism of toxicity briefly described here, A.I. Archakov introduced the term “lethal decay.”

When interacting xenobiotics with microsomal monooxygenases, not radicals can be formed, but stable, highly toxic products leading to intoxication. This version of the toxic effect is called "lethal synthesis". For example, the formation of toxic fluorocitric acid from fluoroacetate, the accumulation of formaldehyde and formic acid during the oxidative transformation of methanol, etc.

All chemical substances, damaging protein synthesis, can be divided into 2 groups. The first of them includes xenobiotics that have an indirect effect on protein synthesis through changes in bioenergy processes, hormonal status, biomembrane permeability, etc. Violation of protein synthesis in the mechanism of their toxic action is a secondary phenomenon that complicates, but does not determine the development of intoxication. An example would be chlorinated hydrocarbons. Thus, tetrachloroalkanes inhibit the incorporation of methionine and lysine into serum and liver proteins.

There is also another mechanism: in the process of metabolism of xenobiotics, active radicals and peroxides are formed, affecting the phospholipids of the membranes of the endoplasmic reticulum and damaging them, which contributes to the disruption of protein synthesis. In particular, inhalation of dichloroethane leads to inhibition of the incorporation of leucine into the liver proteins of mice and causes damage to the polyribosomal structures of hepatocytes. In silicosis, macrophage protein synthesis is inhibited in the lungs; in chronic berylliosis, the processes of incorporation of amino acids into lung proteins are disrupted. Under the influence of lead, the use of methionine for protein synthesis is inhibited; This process is also suppressed by organomercury compounds.

Second group xenobiotics includes compounds that directly inhibit protein synthesis either by interfering with transcription or translation processes. A significant part of xenobiotics disrupts transcription processes, damaging the matrix, i.e. DNA. Under their influence, covalent bonds between nucleotides are disrupted and their functional groups are modified due to the formation of complexes, loss or destruction of sections of the DNA chain. This is exactly how alkylating compounds work. Blocks DNA large group antibiotics. Matrix properties DNA damages big class xenobiotics of the acridine series, intercalating between nucleic acid bases.

As a result mRNA synthesis decreases(matrix ribonucleic acid) and protein biosynthesis is inhibited. Amanitins, products of poisonous mushrooms of the genus Amanita, disrupt transcription by inhibiting the activity of RNA polymerase, which also leads to suppression of protein synthesis.

Xenobiotics, which disrupt translation, can be divided into groups depending on the stage of translation at which they act. For example, at the stage of initiation of the translation process, dihydroxybutyraldehyde and methylglyoxal, synthetic anions - polyvinyl sulfate, polydextran sulfate, etc., and trichothecene fungal toxins act. However, their mechanism of action may be different: aliphatic aldehydes block the attachment of mRNA to ribosomes; polyvinyl sulfate binds to ribosomes at the site where the mRNA attaches; other polyanions block the interaction of ribosomal subunits. Xenobiotics that disrupt translation at the elongation stage may also have different mechanisms of action. For example, the formation of a peptide bond at the elongation stage is blocked by erythromycin and oleandomycin. Diphtheria toxin disrupts translocation. Cycloheximide and its derivatives disrupt translocation in a slightly different way. At the stage of termination of the translation process, tenuazonic acid acts, suppressing the separation of newly formed proteins from ribosomes.

At the conclusion of the consideration protein synthesis disorders xenobiotics will indicate the possibility of suppressing the processes of activation of amino acids and inhibiting the activity of aminoacyl-tRNA synthetases. Substances that act in this way primarily include synthetic analogs of natural amino acids, for example 5-methyltryptophan, 2-methylhistidine, methylhomocysteine, cisfluoroproline, fluorophenylalanine, ethionine, canavanine, etc. These xenobiotics inhibit the incorporation of natural amino acids into proteins due to competitive inhibition corresponding aminoacyl synthetases.

General biological mechanism implementation of toxic effects is also a disorder of bioenergetic processes, usually associated with the mitochondrial structural-metabolic complex.