Primary metabolites and their producers. Primary metabolites

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Whatever the route of photosynthesis, it ultimately ends with the accumulation of energy-rich reserve substances that form the basis for maintaining the life of the cell and, ultimately, the entire multicellular organism. These substances are products of primary metabolism. In addition to their most important function, primary metabolites are the basis for the biosynthesis of compounds that are commonly called products of secondary metabolism. The latter, often conventionally called “secondary metabolites,” owe their existence in nature entirely to the products formed as a result of photosynthesis. It should be noted that the synthesis of secondary metabolites is carried out due to the energy released in mitochondria during the process of cellular respiration.

Secondary metabolites are the subject of study of plant biochemistry, but it is not without interest to familiarize yourself with the diagram (Fig. 1), which shows their biogenetic relationship with direct products of photosynthesis.

Figure 1. Biogenetic relationship of secondary metabolites with direct products of photosynthesis.

Secondary metabolites: pigments, alkaloids, tannins, glycosides, organic acids

Pigments

Among the vacuole pigments, anthocyanins and flavones are the most common.

Anthocyanins belong to the group of glycosides with phenolic groups. Anthocyanins of one group are different from another. An interesting feature of this pigment is that it changes color depending on the pH of the cell sap. When the cell sap is acidic, anthocyanin turns it pink, when it is neutral, it turns purple, and when it is basic, it turns blue.

In some plants, color may change as the flowers develop. For example, borage has buds Pink colour, and mature flowers are blue. It is assumed that in this way the plant signals to insects that it is ready for pollination.

Anthocyanins accumulate not only in flowers, but also in stems, leaves and fruits.

Antochlor is a yellow pigment that belongs to flavonoids. It is less common. Contains anthochlor yellow flowers pumpkin, toadflax, citrus fruits.

The pigment antopheine can also accumulate in the cell sap, turning it dark brown.

Alkaloids include natural heterocyclic compounds containing, in addition to carbon, one or more nitrogen atoms and, less commonly, oxygen atoms in their rings. They exhibit alkaline properties. Alkaloids have high pharmacological activity, so most medicinal plants are classified as alkaloids. More than 20 different alkaloids were found in the pods of the sleeping pill poppy, including morphine, thebaine, codeine, papaverine, etc. As is known, morphine, having an analgesic and anti-shock effect, causes euphoria: with its repeated use, a painful addiction to it develops - drug addiction. Codeine reduces the excitability of the cough center and is part of antitussives. Papaverine is used as an antispasmodic for hypertension, angina, and migraine. Nightshades, buttercups, and lilies are rich in alkaloids.

Many alkaloid-bearing plants are poisonous and are not eaten by animals; they are weakly affected by fungal and bacterial diseases.

Glycosides are sugar derivatives combined with alcohols, aldehydes, phenols and other nitrogen-free substances. When in contact with air, glycosides disintegrate, releasing a pleasant aroma, for example, the smell of hay, brewing tea, etc.

Widest practical use find cardiac glycosides and saponins. Cardiac glycosides are the active principle of such a famous medicinal plant as lily of the valley. Its medicinal properties have been known for a very long time and have not lost their significance to this day. Previously, medicines for dropsy, heart disease, epilepsy, and fever were prepared from lily of the valley.

The name saponins comes from the foaming ability of these compounds. Most representatives of this group have high biological activity, which determines therapeutic effect and, accordingly, the medicinal use of such well-known biostimulants as ginseng, licorice, and aralia.

Tannins (tannins) are phenol derivatives. They have an astringent taste and have antiseptic properties. They accumulate in the cell in the form of colloidal solutions and have yellow, red and Brown color. When iron salts are added, they acquire a bluish-green color, which was previously used to make ink.

Tannins can accumulate in significant quantities in various plant organs. There are many of them in the fruits of quince, persimmon, bird cherry, in oak bark, and in tea leaves.

Tannins are thought to serve a variety of functions. When the protoplast dies, tannins permeate the cell walls and give them resistance to decay. In living cells, tannins protect the protoplast from dehydration. They are also thought to be involved in the synthesis and transport of sugars.

Production of secondary metabolites

Of all the products produced by microbial processes, highest value have secondary metabolites. Secondary metabolites, also called idiolites, are low molecular weight compounds that are not required for growth in pure culture. They are produced by a limited number of taxonomic groups and are often a mixture of closely related compounds belonging to the same chemical group. If the question of the physiological role of secondary metabolites in producer cells has been the subject of serious debate, then their industrial production is of undoubted interest, since these metabolites are biologically active substances: some of them have antimicrobial activity, others are specific enzyme inhibitors, others are growth factors, and many have pharmacological activity. Secondary metabolites include antibiotics, alkaloids, plant growth hormones and toxins. The pharmaceutical industry has developed highly sophisticated methods for screening (mass testing) microorganisms for the ability to produce valuable secondary metabolites.

The production of such substances served as the basis for the creation of a number of branches of the microbiological industry. The first in this series was the production of penicillin; The microbiological method for producing penicillin was developed in the 1940s and laid the foundation for modern industrial biotechnology.

Antibiotic molecules are very diverse in composition and mechanism of action on the microbial cell. At the same time, due to the emergence of resistance of pathogenic microorganisms to old antibiotics, there is a constant need for new ones. In some cases, natural microbial antibiotic products can be chemically or enzymatically converted into so-called semisynthetic antibiotics with higher therapeutic properties.

Antibiotics - organic compounds. They are synthesized by a living cell and in small concentrations are capable of slowing down the development or completely destroying species of microorganisms that are sensitive to them. They are produced not only by the cells of microorganisms and plants, but also by animal cells. Antibiotics of plant origin are called phytoncides. These are chloreline, tomatine, sativine, obtained from garlic, and aline, isolated from onions.

The growth of microorganisms can be characterized as an S - shaped curve. The first stage is the stage of rapid growth, or logarithmic, which is characterized by the synthesis of primary metabolites. Next comes a phase of slow growth, when the increase in cell biomass slows down sharply. Microorganisms that produce secondary metabolites first go through a stage of rapid growth, the tropophase, during which the synthesis of secondary substances is insignificant. As growth slows due to depletion of one or more essential nutrients in the culture medium, the microorganism enters idiophase; It is during this period that idiolites are synthesized. Idiolytes, or secondary metabolites, do not play a clear role in metabolic processes; they are produced by cells to adapt to environmental conditions, for example, for protection. They are synthesized not by all microorganisms, but mainly by filamentous bacteria, fungi and spore-forming bacteria. Thus, producers of primary and secondary metabolites belong to different taxonomic groups.

The characteristics of the cultural growth of these microorganisms must be taken into account during production. For example, in the case of antibiotics, most microorganisms during the tropophase are sensitive to their own antibiotics, but during the idiophase they become resistant to them.

To protect antibiotic-producing microorganisms from self-destruction, it is important to quickly reach the idiophase and then culture the microorganisms in this phase. This is achieved by varying cultivation regimes and the composition of the nutrient medium at the stages of fast and slow growth.

Plant cell and tissue cultures are considered a potential source of specific secondary metabolites, which include compounds such as alkaloids, steroids, oils and pigments. Many of these substances are still obtained by extraction from plants. Microbiological industry methods are not currently applicable to all plant species. With the exception of some plant species, suspension and callus cell cultures synthesize secondary metabolites in smaller quantities than whole plants. In this case, the growth of biomass in the fermenter can be significant.

A new approach aimed at increasing the yield of secondary metabolites is the immobilization of plant cells and tissues. The first successful attempt to record whole cells was carried out in 1966 by Mosbach. He fixed the cells of the lichen Umbilicaria pustulata in a polyacrylamide gel. The following year, van Wetzel grew animal embryonic cells immobilized on DEAE (dextran-based diethylaminoethyl Sephadex) microbeads. After this, the cells were immobilized on different substrates. These were mainly microbial cells.

Cell immobilization methods are divided into 4 categories:

Immobilization of cells or subcellular organelles in an inert substrate. For example, cells of Catharanthus roseus, Digitalis lanata in alginate, agarose beads, gelatin, etc. The method involves enveloping cells in one of various cementing media - alginate, agar, collagen, polyacrylamide.

Adsorption of cells on an inert substrate. Cells adhere to charged beads made of alginate, polystyrene, and polyacrylamide. The method was used in experiments with animal cells, as well as cells of Saccharomyces uvarum, S. cerevisiae, Candida tropicalis, E. coli.

Adsorption of cells on an inert substrate using biological macromolecules (such as lectin). Rarely used, there is information about experiments with different lines human cells, sheep blood erythrocytes adsorbed on protein-coated agarose.

Covalent binding to another inert carrier such as CMC. Very rarely used, successful immobilization is known for Micrococcus luteus. Experiments were mainly carried out on the immobilization of animal cells and microorganisms.

IN Lately Interest in the immobilization of plant cells has increased significantly, this is due to the fact that immobilized cells have certain advantages over callus and suspension cultures when used to obtain secondary metabolites.

Physiological basis of the advantages of immobilized plant cells over traditional cultivation methods

There is extensive evidence in the literature that there is a positive correlation between the accumulation of secondary metabolites and the degree of differentiation in cell culture. In addition, lignin, for example, is deposited in tracheids and vascular elements of xylem only after the completion of differentiation processes, which was shown in experiments both in vivo and in vitro. The data obtained indicate that differentiation and accumulation of secondary metabolic products occurs at the end of the cell cycle. As growth decreases, differentiation processes accelerate.

A study of the content of alkaloids accumulated by many plants in vitro showed that compact, slowly growing cell cultures contain alkaloids in larger quantities than loose, rapidly growing cultures. Organization of cells is necessary for their normal metabolism. The presence of organization in the tissue and its subsequent effect on various physical and chemical gradients are clear indicators by which high- and low-yield crops are distinguished. It is obvious that immobilization of cells provides conditions leading to differentiation, streamlines the organization of cells and thereby contributes to a high yield of secondary metabolites.

Immobilized cells have a number of advantages:

1. Cells immobilized in or on an inert substrate form biomass much more slowly than those growing in liquid suspension cultures.

What is the connection between growth and metabolism? What does cellular organization and differentiation have to do with it? It is believed that this relationship is due to two types of mechanisms. The first mechanism is based on the fact that growth determines the degree of cell aggregation, having an indirect effect on the synthesis of secondary metabolites. Organization in in this case is the result of cell aggregation, and a sufficient degree of aggregation can only be obtained in slowly growing cultures. The second mechanism is related to growth rate kinetics and suggests that the “primary” and “secondary” metabolic pathways compete differently for precursors in fast and slow growing cells. If environmental conditions are favorable for rapid growth, then primary metabolites are synthesized first. If rapid growth is blocked, then the synthesis of secondary metabolites begins. Thus, the low growth rate of immobilized cells contributes to a high yield of metabolites.

2. In addition to slow growth, immobilization of cells allows them to grow in close physical contact with each other, which also has a beneficial effect on chemical contacts.

In a plant, any cell is surrounded by other cells, but its position changes during ontogenesis as a result of the division of both this and surrounding cells. The degree and type of differentiation of this cell depends on the position of the cell in the plant. Therefore, the physical environment of a cell influences its metabolism. How? The regulation of the synthesis of secondary metabolites is under both genetic and epigenetic (extranuclear) control, that is, any changes in the cytoplasm can lead to quantitative and qualitative changes in the formation of secondary metabolites. In turn, the cytoplasm is a dynamic system influenced by the environment.

From external conditions metabolism is significantly influenced by 2 important factors: oxygen concentration and carbon dioxide, as well as lighting levels. Light plays a role both in the process of photosynthesis and in physiological processes such as cell division, microfibril orientation, and enzyme activation. The intensity and wavelength of the light wave are determined by the position of the cell in the mass of other cells, that is, they depend on the degree of organization of the tissue. In an organized structure, there are centrifugal concentration gradients of O2 and CO2, which play an extremely important role in the differentiation process.

Thus, secondary metabolism in large aggregates of cells with small area-to-volume (S/V) ratios differs from that of isolated cells and small groups of cells as a result of gas concentration gradients. Gradients of growth regulators, nutrients, and mechanical pressure operate similarly. The environmental conditions of dispersed cells and cells in the form of aggregates are different, so their metabolic pathways are also different.

3. The yield of secondary metabolites can also be regulated by changing the chemical composition of the environment.

Changing the composition of the medium for callus and suspension cultures is accompanied by certain physical manipulations with cells, which can lead to damage or contamination of the cultures. These difficulties can be overcome by circulating large volumes of nutrient medium around physically immobile cells, allowing for sequential chemical treatments.

4. In some cases, problems arise with the isolation of idiolites.

When using immobilized cells, it is relatively easy to process them chemicals, inducing the release of the required products. It also reduces feedback inhibition, which limits the synthesis of substances due to their accumulation within the cell. Cultivated cells of some plants, for example, Capsicum frutescens, release secondary metabolites into the environment, and the system of immobilized cells allows the selection of products without damaging the crops. Thus, cell immobilization facilitates easy isolation of idiolites.

List of used literature:

1. “Microbiology: a dictionary of terms”, Firsov N.N., M: Bustard, 2006.

2. Medicinal raw materials of plant and animal origin. Pharmacognosy: textbook/ed. G.P.Yakovleva. St. Petersburg: SpetsLit, 2006. 845 p.

3. Shabarova Z. A., Bogdanov A. A., Zolotukhin A. S. Chemical foundations of genetic engineering. - M.: Moscow State University Publishing House, 2004, 224 p.

4. Chebyshev N.V., Grineva G.G., Kobzar M.V., Gulyankov S.I. Biology.M., 2000

Medicinal raw materials of plant and animal origin. Pharmacognosy: textbook/ed. G.P.Yakovleva. St. Petersburg: SpetsLit, 2006. 845 p.

Shabarova Z. A., Bogdanov A. A., Zolotukhin A. S. Chemical foundations of genetic engineering. - M.: Moscow State University Publishing House, 2004, 224 p.

Diauxia- the appearance of one or more transitional (i.e. temporary) growth phases in the culture. This occurs when bacteria are in an environment containing two or more alternative sources nutrition. Bacteria often use one source in preference to another until the first is depleted. Then the bacteria switch to another food source. However, growth slows down noticeably even before the change in food source occurs. An example is E. coli, a bacterium typically found in the intestines. It can use glucose or lactose as a source of energy and carbon. If both carbohydrates are present, glucose is used first and then growth slows until lactose fermenting enzymes are produced.

Formation of primary and secondary metabolites

Primary metabolites- These are metabolic products necessary for growth and survival.
Secondary metabolites- metabolic products that are not required for growth and are not essential for survival. However, they do useful features and often protect against the action of other competing microorganisms or inhibit their growth. Some of them are toxic to animals, so they can be used as chemical weapons. During the most active periods of growth, they are most often not produced, but begin to be produced when growth slows down, when reserve materials become available. Secondary metabolites are some important antibiotics.

Measuring the growth of bacteria and fungi in culture

In the previous section we analyzed typical bacterial growth curve. One would expect that the same curve characterizes the growth of yeast (single-celled fungi) or the growth of any culture of microorganisms.

When analyzing bacterial growth or yeast, we can either directly count the number of cells or measure some parameters dependent on the number of cells, such as the turbidity of the solution or gas production. Typically, a small number of microorganisms are inoculated into a sterile nutrient medium and the culture is grown in an incubator at optimal temperature growth. The remaining conditions should be as close to optimal as possible (Section 12.1). Growth should be measured from the time of inoculation.

Usually in scientific research adhere to good rule - carry out the experiment in several repetitions and place control samples where possible and necessary. Some height measurement techniques require certain skills and even in the hands of specialists they are not very accurate. Therefore, it makes sense to perform, if possible, two samples (one repetition) in each experiment. A control sample in which no microorganisms were added to the culture medium will show whether you are truly working sterilely. With enough experience, you can master all the methods described, so we advise you to practice them first before using them on your project. The number of cells can be determined in two ways, namely by counting either the number of viable cells or the total number of cells. The viable cell count is the number of living cells only. The total cell number is the total number of both living and dead cells; this indicator is usually easier to determine.

Questions:

1. Metabolism. Primary and secondary metabolism.

2. Features of cellular metabolism.

3. The cell as an open thermodynamic system. Types of work in the cage. Macroergic compounds.

4. Enzymes: structure (prostatic group, coenzymes) and functions. Classification of enzymes

5. Secondary metabolites, classification, role in plant life, human use. Formation of pigments, toxins, aromatic substances by microorganisms (fungi, bacteria).

1. Metabolism (metabolism) – the totality of all chemical reactions walking in a cage.

Metabolites - metabolic products.

On the formation of hormones in cells (ethylene, suppress the synthesis of IAA);

Inhibit rhizogenesis and cell elongation;

They are phytotoxins (have an antimicrobial effect);

With their help, one plant can act on another,

Tannins increase the resistance of trees to fungal infections.

Are used in medicine for sterilization, medicines (salicylic acid), in industry as dyes.

5.2. Alkaloids – heterocyclic compounds containing one or more nitrogen atoms in the molecule. About 10,000 alkaloids are known. They are found in 20% of plants and are most common among angiosperms (flowering) plants. Alkaloids are rare in bryophytes and pteridophytes.

Alkaloids are synthesized from amino acids: ornithine, tyrosine, lysine, tryptophan, phenylalanine, histidine, atranilic acid.

They accumulate in actively growing tissues, in the cells of the epidermis and hypodermis, in the sheaths of vascular bundles, and in laticifers. They can accumulate not in those cells where they are formed, but in others. For example, nicotine is produced in the roots and accumulates in the leaves. Usually their concentration is tenths or hundredths of a percent, but cinchona contains 15 - 20% alkaloids. Different plants may contain different alkaloids. Alkaloids are found in leaves, bark, roots, and wood.

Functions alkaloids:

regulate plant growth (IAA), protect plants from being eaten by animals.

Are used alkaloids

as medicines: codeine (for cough), morphine (painkiller), caffeine (for nervous and cardiovascular diseases), quinine (for malaria). Atropine, pilocarpine, strychnine, ephedrine are poisonous, but in small doses they can be used as medicines.;

Nicotine and anabasine are used to control insects.

5.3. Isoprenoids (terpenoids) - compounds composed of several isoprene units (C5H8 - isoprene) and having the general formula (C5H8)n. Thanks to additional groups (radicals), isoprenoids can have a number of carbon atoms in the molecule that is not a multiple of 5. Terpenes include not only hydrocarbons, but also compounds with alcohol, aldehyde, keto, lactone and acid groups.

Polyterpenes – rubber, gutta.

Terpenoids are gibberellic acid (gibberellins), abscisic acid, cytokinins. They do not dissolve in water. Found in chloroplasts and membranes.

Carotenoids are yellow to red-violet in color, formed from lycopene, and soluble in fats.

Isoprenes included

contains oil from pine needles, cones, flowers, fruits, wood;

resins, latex, essential oils.

Functions:

Protect plants from bacteria, insects and animals; some of them are involved in closing wounds and protecting against insects.

These include hormones (cytokinins, gibberellins, abscisic acid, brassinosteroids);

Carotenoids participate in the light phase of photosynthesis, entering the SSC, and protect chlorophyll from photo-oxidation;

Sterols are part of membranes and affect their permeability.

Use as medicines (camphor, menthol, cardiac glycosides), vitamin A. They are the main components of essential oils, so they are used in perfumes and contained in repellents. They are part of rubber. Geraniol alcohol is found in rose oil, bay leaf oil, orange flower oil, jasmine oil, and eucalyptus oil).

5.4. Synthesis of secondary metabolites

characterized by some features:

1) their precursors are a small number of primary metabolites. For example, 8(?) amino acids are required for the synthesis of alkaloids, phenylalanine or tyrosine for the synthesis of phenols, and mevalonic acid for the synthesis of isoprenoids;

2) many secondary metabolites are synthesized in different ways;

3) special enzymes participate in the synthesis.

Secondary metabolites are synthesized in the cytosol, endoplasmic reticulum, and chloroplasts.

5.5. Localization of secondary metabolites

They accumulate in vacuoles (alkaloids, phenols, betalains, cyanogenic glycosides, glucosinolates), in the periplasmic space (phenols). After synthesis, isoprenoids leave the cell.

Secondary metabolites are rarely distributed evenly in tissues. They often accumulate in idioblasts, laticifers, special canals and passages.

Idioblasts (from Greek Idios peculiar) - single cells related to excretory tissues and differing from neighboring cells in shape and structure. They are found in the epidermis of stems or leaves (only in the epidermis?).

The sites of synthesis and localization are often separated. For example, nicotine is synthesized in the roots and accumulates in the leaves.

Secondary metabolites are released into the external environment with the help of excretory tissues (glandular cells, glandular hairs - trichomes).

Isolation is not typical for alkaloids.

The synthesis and accumulation of secondary metabolites in tissues depends mainly on the type of plant, sometimes on the stage of ontogenesis or age, and on external conditions. Distribution in tissues depends on the plant type.

5.6. Functions of secondary metabolites

During the discovery of secondary metabolites, there were different opinions about their importance in plant life. They were considered unnecessary, waste, (their synthesis) a metabolic dead end, products of detoxification of poisonous primary metabolites, such as free amino acids.

At present, many are already known functions of these connections, for example storage, protective. Alkaloids are a supply of nitrogen for cells; phenolic compounds can be a respiratory substrate. Secondary metabolites protect plants from biopathogens. Essential oils, which are a mixture of secondary metabolites, have antimicrobial and antifungicidal properties. Some secondary metabolites, breaking down during hydrolysis, form poison - hydrocyanic acid, coumarin. Secondary metabolites are phytoalexins, substances formed in response to infection and involved in hypersensitivity reactions.

Anthocyanins, carotenoids, betalains, which provide the color of flowers and fruits, promote plant reproduction and seed dissemination.

Secondary metabolites stop the germination of seeds of competing species.

Literature:

1. Mercer E. Introduction to plant biochemistry. T. 2. – M. “Mir”, 1986.

2. (ed.). Physiology of plants. – M. “Academy”, 2005. P. 588 – 619.

3. Harborne J. Introduction to Environmental Biochemistry. – M. “Mir”, 1985.

4. L. Biochemistry of plants. – M. “ graduate School", 1986. pp. 312 – 358.

5. , -AND. Physiology woody plants. – M. “Forest Industry”, 1974. 421 p.

6. L. Biochemistry of plants. - M. VSh. 1986. 502 p.

Of all the products obtained through microbial processes, secondary metabolites are the most important. Secondary metabolites, also called idiolites, are low molecular weight compounds that are not required for growth in pure culture. They are produced by a limited number of taxonomic groups and are often a mixture of closely related compounds belonging to the same chemical group. If the question of the physiological role of secondary metabolites in producer cells has been the subject of serious debate, then their industrial production is of undoubted interest, since these metabolites are biologically active substances: some of them have antimicrobial activity, others are specific enzyme inhibitors, and others are growth factors. , many have pharmacological activity. Secondary metabolites include antibiotics, alkaloids, plant growth hormones and toxins. The pharmaceutical industry has developed highly sophisticated methods for screening (mass testing) microorganisms for the ability to produce valuable secondary metabolites.

Antibiotics are organic compounds. They are synthesized by a living cell and in small concentrations are capable of slowing down the development or completely destroying species of microorganisms that are sensitive to them. They are produced not only by the cells of microorganisms and plants, but also by animal cells. Antibiotics of plant origin are called phytoncides. These are chloreline, tomatine, sativine, obtained from garlic, and aline, isolated from onions.

Most spices, seasonings, teas and other beverages such as coffee and cocoa owe their individual properties (taste and aroma) to pharmacologically active secondary metabolites of the plants that contain them. Although some of these active compounds (such as vanillin, ephedrine, and caffeine) are produced by semi- or total synthesis, high prices are still paid for compounds isolated from natural sources, especially if they are intended to be used as food additives and flavors.

Some biologically active secondary metabolites have found use as drugs or as model compounds for drug synthesis and semisyntheses. However, it is often forgotten that natural products often serve as chemical models for the design and total synthesis of new drug structures. For example, meperidine (Demerol), pentazocine (Talwin) and propoxyphene (Darvon) are completely synthetic analgesics for which opiates such as morphine and codeine were models, while aspirin is a simple derivative of salicylic acid, originally derived from willow (Salix SPP.).

Compared to the relatively low cost of primary and bulk metabolites, secondary plant metabolites are often priced from a few dollars to several thousand dollars per kilogram. For example, purified opium alkaloids (codeine and morphine) are valued at between $650 and $1,250 per kilogram, while rare volatile (essential) oils such as rose oil are often valued at over $2,000 to $3,000 per kilogram. Catharanthus antitumor alkaloids have a wholesale value of about $5,000 per gram, and their retail value can reach $20,000 per gram. Natural products often have highly complex structures with many chiral centers that can determine biological activity. Such complex compounds cannot be synthesized artificially. A good example such a metabolite with high degree structural complexity is a natural plant insecticide called azadirachtin.

Economically important characteristics of primary and secondary metabolites. Most of them can be obtained from plant materials by steam distillation or extraction with organic solvents, and (with the exception of biopolymers, natural rubber, condensed tannins and substances with high molecular weight, polysaccharides such as gums, pectin and starch) they have, as generally relatively low molecular weight (typically less than 2000).

Economically important substances of plant origin include the enzymes papain and chymopapain (enzymes obtained from papaya (Carica Papaya), which are used in medicinal purposes, bromelain (a milk protein digesting and clotting enzyme from pineapple juice) and malt extract (a barley product that contains a starch-digesting enzyme).

The production and use of specialty plant proteins from plant cells is of limited value for several reasons. Firstly, their chemical structure imposes certain restrictions on their use as biologically active compounds, which can act as drugs and pesticides. For example, most proteins cannot be readily absorbed through the skin of mammals or the exoskeleton of insects, and most also cannot be administered orally (except for local effect) because they are susceptible to degradation by digestive proteolytic enzymes. For reproducible systemic effects produced, polypeptides (such as chymopapain) must be administered by injection. Thus, proteins are not as readily bioavailable as secondary metabolites ( protein products), which complicates the development of final products from them and their use. For example, some potentially useful proteins can be rapidly degraded due to physicochemical instability. Currently, technologies are already available for the insertion and expression in bacteria and yeast of genes encoding the synthesis of valuable polypeptides. However, in this case, difficulties arise for the production of complex secondary metabolites due to the nature of the secondary biosynthesis of metabolites in plants. Proteins are the direct products of genes, while secondary metabolites are usually synthesized through the combined actions of many gene products (enzymes) (Y. Aharonowitz). There are many genes responsible for the biosynthesis of economically important secondary metabolites (many genes are required for each biosynthetic pathway leading to the production of a secondary metabolite). In addition, genetically modified microorganisms have many enzymes in their biosynthetic pathway that can catalyze unwanted adverse reactions with the desired metabolite or intermediate. Thus, at least in the near future, plants or plant cells are likely to act as sources for most of the bioactive plant components.

Under metabolism or metabolism, understand the totality of chemical reactions in the body that provide it with substances to build the body and energy to maintain life. Some of the reactions turn out to be similar for all living organisms (the formation and breakdown of nucleic acids, proteins and peptides, as well as most carbohydrates, some carboxylic acids, etc.) and are called primary metabolism (or primary metabolism).

In addition to primary metabolic reactions, there are a significant number of metabolic pathways that lead to the formation of compounds that are characteristic only of certain, sometimes very few, groups of organisms.

These reactions, according to I. Capek (1921) and K. Pekh (1940), are united by the term secondary metabolism , or exchange, and their products are called products secondary metabolism, or secondary compounds (sometimes secondary metabolites).

Secondary connections are formed predominantly in vegetatively sedentary groups of living organisms - plants and fungi, as well as in many prokaryotes.

In animals, secondary metabolic products are rarely formed, but often come from outside along with plant foods.

The role of secondary metabolic products and the reasons for their appearance in one group or another are different. In the most general form, they are attributed adaptive significance and, in a broad sense, protective properties.

The rapid development of the chemistry of natural compounds over the past three decades, associated with the creation of high-resolution analytical instruments, has led to the fact that the world "secondary connections" expanded significantly. For example, the number of alkaloids known today is approaching 5,000 (according to some sources, 10,000), phenolic compounds - 10,000, and these numbers are growing not only every year, but also every month.

Any plant material always contains a complex set of primary and secondary compounds, which, as already mentioned, determine the versatile nature of the action of medicinal plants. However, the role of both in modern herbal medicine is still different.

There are relatively few known objects whose use in medicine is determined primarily by the presence of primary compounds in them. However, in the future it is possible that their role in medicine will increase and their use as sources of new immunomodulatory agents can be obtained.

Secondary metabolic products are used in modern medicine much more often and widely. This is due to their noticeable and often very “bright” pharmacological effect.

Formed on the basis of primary compounds, they can either accumulate in pure form, or undergo glycosylation during metabolic reactions, i.e. appear attached to a molecule of some sugar.

As a result of glycosylation, molecules appear - heterosides, which differ from secondary compounds, as a rule, in better solubility, which facilitates their participation in metabolic reactions and in this sense is of great biological importance.

Glycosylated forms of any secondary compounds are usually called glycosides.

Substances of primary synthesis are formed in the process of assimilation, i.e. transformation of substances entering the body from the outside into substances of the body itself (protoplast of cells, reserve substances, etc.).

Substances of primary synthesis include amino acids, proteins, lipids, carbohydrates, enzymes, vitamins and organic acids.

Lipids (fats), carbohydrates (polysaccharides) and vitamins are widely used in medical practice (the characteristics of these groups of substances are given in the relevant topics).

Squirrels, along with lipids and carbohydrates, make up the structure of cells and tissues of a plant organism, participate in biosynthesis processes, and are an effective energy material.

Proteins and amino acids of medicinal plants have a nonspecific beneficial effect on the patient’s body. They influence protein synthesis, create conditions for enhanced synthesis of immune bodies, which leads to an increase in the body's defenses. Improved protein synthesis also includes enhanced enzyme synthesis, resulting in improved metabolism. Biogenic amines and amino acids play an important role in the normalization of nervous processes.

Squirrels- biopolymers, the structural basis of which is made up of long polypeptide chains, built from α-amino acid residues connected to each other by peptide bonds. Proteins are divided into simple (when hydrolyzed they yield only amino acids) and complex - in them the protein is associated with substances of a non-protein nature: with nucleic acids (nucleoproteins), polysaccharides (glycoproteins), lipids (lipoproteins), pigments (chromoproteins), metal ions (metalloproteins) , phosphoric acid residues (phosphoproteins).

At the moment, there are almost no objects of plant origin, the use of which would be determined mainly by the presence of proteins in them. However, it is possible that in the future modified plant proteins could be used as means of regulating metabolism in the human body.

Lipids - fats and fat-like substances that are derivatives of higher fatty acids, alcohols or aldehydes.

They are divided into simple and complex.

To simple These are lipids whose molecules contain only residues of fatty acids (or aldehydes) and alcohols. Of the simple lipids found in plants and animals are fats and fatty oils, which are triacylglycerols (triglycerides) and waxes.

The latter consist of esters of higher fatty acids of mono- or diatomic higher alcohols. Close to fats are prostaglandins, which are formed in the body from polyunsaturated fatty acids. By chemical nature, these are derivatives of prostanoic acid with a skeleton of 20 carbon atoms and containing a cyclopentane ring.

Complex lipids divided by two large groups:

phospholipids and glycolipids (i.e., compounds that have a phosphoric acid residue or a carbohydrate component in their structure). As part of living cells, lipids play an important role in life support processes, forming energy reserves in plants and animals.

Nucleic acids - biopolymers, the monomer units of which are nucleotides consisting of a phosphoric acid residue, a carbohydrate component (ribose or deoxyribose) and a nitrogenous (purine or pyrimidine) base. There are deoxyriboucleic acids (DNA) and ribonucleic acids (RNA). Nucleic acids from plants are not yet used for medicinal purposes.

Enzymes occupy a special place among proteins. The role of enzymes in plants is specific - they are catalysts for most chemical reactions.

All enzymes are divided into 2 classes: one-component and two-component. Single-component enzymes consist only of protein,

two-component - from protein (apoenzyme) and non-protein part (coenzyme). Vitamins can be coenzymes.

The following enzyme preparations are used in medical practice:

- "Niguedaza " - from the seeds of nigella damascena - Nigella damascena, fam. Ranunculaceae - Ranunculaceae. The drug is based on a lipolytic enzyme that causes the hydrolytic breakdown of fats of plant and animal origin.

The drug is effective for pancreatitis, enterocolitis and age-related decrease in the lipolytic activity of digestive juice.

- "Karipazim" and "Lekozim" - from the dried milky juice (latex) of papaya (melon tree) - Carica papaya L., fam. papaeves - Cariacaceae.

At the heart of "Karipazim"" - the sum of proteolytic enzymes (papain, chymopapain, peptidase).

Used for third degree burns, accelerates the rejection of scabs, cleans granulating wounds from purulent-necrotic masses.

At the heart of "Lekozima"" - proteolytic enzyme papain and mucolytic enzyme lysozyme. Used in orthopedic, traumatological and neurosurgical practice for intervertebral osteochondrosis, as well as in ophthalmology for resorption of exudates.

Organic acids, along with carbohydrates and proteins, they are the most common substances in plants.

They take part in plant respiration, biosynthesis of proteins, fats and other substances. Organic acids refer to substances of both primary synthesis (malic, acetic, oxalic, ascorbic) and secondary synthesis (ursolic, oleanolic).

Organic acids are pharmacologically active substances and participate in the overall effect of drugs and dosage forms plants:

Salicylic and ursolic acids have anti-inflammatory effects;

Apple and succinic acid- donors of energy groups, help increase physical and mental performance;

Ascorbic acid - vitamin C.

Vitamins- a special group of organic substances that perform important biological and biochemical functions in living organisms. These organic compounds of various chemical natures are synthesized mainly by plants, as well as microorganisms.

Humans and animals that do not synthesize them require vitamins in very small quantities compared to nutrients (proteins, carbohydrates, fats).

More than 20 vitamins are known. They have letter designations, chemical names and names characterizing their physiological action. Vitamins are classified to water-soluble (ascorbic acid, thiamine, riboflavin, pantothenic acid, pyridoxine, folic acid, cyanocobalamin, nicotinamide, biotin)

and fat-soluble (retinol, phylloquinone, calciferols, tocopherols). To vitamin-like The substances include some flavonoids, lipoic, orotic, pangamic acids, choline, inositol.

Biological role vitamins are varied. A close connection has been established between vitamins and enzymes. For example, most B vitamins are precursors to coenzymes and prosthetic enzyme groups.

Carbohydrates- a broad class of organic substances, which includes polyoxycarbonyl compounds and their derivatives. Depending on the number of monomers in the molecule, they are divided into monosaccharides, oligosaccharides and polysaccharides.

Carbohydrates consisting exclusively of polyoxycarbonyl compounds are called homosides, and their derivatives, the molecule of which contains residues of other compounds, are called heterosides. Heterosides include all types of glycosides.

Mono- and oligosaccharides are normal components of any living cell. In cases where they accumulate in significant quantities, they are classified as so-called ergastic substances.

Polysaccharides, as a rule, always accumulate in significant quantities as waste products of the protoplast.

Monosaccharides and oligosaccharides are used in their pure form, usually in the form of glucose, fructose and sucrose. Being energy substances, mono- and oligosaccharides are usually used as excipients in the manufacture of various dosage forms.

Plants are sources of these carbohydrates ( sugar cane, beets, grapes, hydrolyzed wood of a number of conifers and woody angiosperms).

Various forms are synthesized in plants polysaccharides, which differ from each other both in structure and in the functions performed. Polysaccharides are widely used in medicine in various forms. In particular, starch and its hydrolysis products, as well as cellulose, pectin, alginates, gums and mucilages are widely used.

Cellulose (fiber) - polymer that makes up the bulk of plant cell walls. It is believed that the fiber molecule in different plants contains from 1,400 to 10,000 β-D-glucose residues.

Starch and inulin belong to storage polysaccharides.

Starch is 96-97.6% composed of two polysaccharides: amylose (linear glucan) and amylopectin (branched glucan).

It is always stored in the form of starch grains during the period of active photosynthesis. Among the representatives of the family. Asteraceae And Satrapi/aseae Fructosans (inulin) accumulate, especially in large quantities in underground organs.

Slime and gum (gum) - mixtures of homo- and heterosaccharides and polyuronides. Gums consist of heteropolysaccharides with the obligatory participation of uronic acids, the carbonyl groups of which are associated with Ca 2+, K + and Mg 2+ ions.

Based on their solubility in water, gums are divided into 3 groups:

Arabic, highly soluble in water (apricot and arabic);

Bassorinaceae, poorly soluble in water, but highly swelling in it (tragacanth)

And cerazine, poorly soluble and poorly swelling in water (cherry).

Slime, unlike gums, can be neutral (do not contain uronic acids), and also have a lower molecular weight and are highly soluble in water.

Pectic substances- high molecular weight heteropolysaccharides, the main structural component of which is β-D-galacturonic acid (polygalacturonide).

In plants, pectic substances are present in the form of insoluble protopectin - a polymer of methoxylated polygalacturonic acid with galactan and araban of the cell wall: polyuronide chains are interconnected by Ca 2+ and Mg 2+ ions.

Substances of secondary metabolism

Substances of secondary synthesis are formed in plants as a result

Dissimilation.

Dissimilation is the process of decomposition of substances of primary synthesis to more simple substances, accompanied by the release of energy. From these simple substances, with the expenditure of released energy, substances of secondary synthesis are formed. For example, glucose (a substance of primary synthesis) breaks down to acetic acid, from which mevalonic acid is synthesized and, through a series of intermediate products, all terpenes.

Substances of secondary synthesis include terpenes, glycosides, phenolic compounds, and alkaloids. All of them participate in metabolism and perform certain important functions for plants.

Substances of secondary synthesis are used in medical practice much more often and wider than substances of primary synthesis.

Each group of plant substances is not isolated and is inextricably linked with other groups by biochemical processes.

For example:

Most phenolic compounds are glycosides;

Bitters from the terpene class are glycosides;

Plant steroids are terpenes in origin, while cardiac glycosides, steroid saponins and steroid alkaloids are glycosides;

Carotenoids, derivatives of tetraterpenes, are vitamins;

Monosaccharides and oligosaccharides are part of glycosides.

All plants contain substances of primary synthesis, substances of secondary

plants accumulate individual species, genera, families.

Secondary metabolites are formed primarily in vegetatively sedentary groups of living organisms - plants and fungi.

The role of secondary metabolic products and the reasons for their appearance in one or another systematic group are different. In the most general form, they are attributed adaptive significance and, in a broad sense, protective properties.

In modern medicine, secondary metabolic products are used much more widely and more often than primary metabolites.

This is often associated with a very strong pharmacological effect and multiple effects on various systems and organs of humans and animals. They are synthesized on the basis of primary compounds and can accumulate either in free form, or during metabolic reactions they undergo glycosylation, i.e. they bind to some sugar.

Alkaloids - nitrogen-containing organic compounds of a basic nature, mainly of plant origin. The structure of alkaloid molecules is very diverse and often quite complex.

Nitrogen is usually located in heterocycles, but is sometimes found in the side chain. Most often, alkaloids are classified based on the structure of these heterocycles, or in accordance with their biogenetic precursors - amino acids.

The following main groups of alkaloids are distinguished: pyrrolidine, pyridine, piperidine, pyrrolizidine, quinolizidine, quinazoline, quinoline, isoquinoline, indole, dihydroindole (betalaines), imidazole, purine, diterpene, steroidal (glycoalkaloids) and alkaloids without heterocycles (protoalkaloids). Many of the alkaloids have specific, often unique physiological effects and are widely used in medicine. Some alkaloids are strong poisons (for example, curare alkaloids).

Anthracene derivatives- a group of natural compounds of yellow, orange or red color, based on the structure of anthracene. They can have different degrees of oxidation of the middle ring (anthrone, anthranol and anthraquinone derivatives) and carbon skeleton structure (monomeric, dimeric and condensed compounds). Most of them are derivatives of chrysacin (1,8-dihydroxyanthraquinone). Less common are derivatives of alizarin (1,2-dihydroxyanthraquinone). In plants, anthracene derivatives can be found in free form (aglycones) or in the form of glycosides (anthraglycosides).

Withanolides - group of phytosteroids. Currently, several series of this class of compounds are known. Withanolides are polyhydroxysteroids that have a 6-membered lactone ring at position 17, and a keto group at C1 in ring A.

Glycosides - widespread natural compounds that decompose under the influence of various agents (acid, alkali or enzyme) into a carbohydrate part and an aglycone (genin). The glycosidic bond between sugar and aglycone can be formed with the participation of O, N or S atoms (O-, N- or S-glycosides), as well as due to C-C atoms(C-glycosides).

O-glycosides are most widespread in the plant world). Glycosides can differ from each other both in the structure of the aglycone and in the structure of the sugar chain. Carbohydrate components are represented by monosaccharides, disaccharides and oligosaccharides, and, accordingly, glycosides are called monosides, biosides and oligosides.

Peculiar groups of natural compounds are cyanogenic glycosides And thioglycosides (glucosinolates).

Cyanogenic glycosides can be presented as derivatives of α-hydroxynitriles containing hydrocyanic acid.

They are widespread among plants of the family. Ros aseae, subfamily Рripoideae, concentrating predominantly in their seeds (for example, amygdalin and prunasin glycosides in seeds Atugdalus sottinis, Arteniaca vi1garis).

Thioglycosides (glucosinolates) are currently considered as derivatives of a hypothetical anion - glucosinolate, hence the second name.

Glucosinolates have so far been found only in dicotyledonous plants and are characteristic of the family. Вrassi saseae, Sarraridaceae, Resedaceae and other representatives of order Sarpa1es.

In plants they are contained in the form of salts with alkali metals, most often with potassium (for example, sinigrin glucosinolate from seeds Вrassica jipsea And V.nigra.

Isoprenoids - a broad class of natural compounds considered

as a product of the biogenic transformation of isoprene.

These include various terpenes, their derivatives - terpenoids and steroids. Some isoprenoids are structural fragments of antibiotics, some - vitamins, alkaloids and animal hormones.

Terpenes and terpenoids- unsaturated hydrocarbons and their derivatives of composition (C 5 H 8) n, where n = 2 or n > 2. Based on the number of isoprene units, they are divided into several classes: mono-, sesqui-, di-, tri-, tetra - and polyterpenoids.

Monoterpenoids (C 10 H 16) and sesquiterpenoids (C 15 H 24) are common components of essential oils.

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