Hormones

Hormones

Hormones (gr. hormao- I set in motion) - these are substances produced by specialized cells and regulating the metabolism in individual organs and throughout the body as a whole. All hormones are characterized by high specificity of action and high biological activity.

A number of hereditary and acquired diseases are associated with a violation of hormonal metabolism, accompanied by serious problems in the development and functioning of the body ( dwarfism, And gigantism, sugar And non-sugar diabetes, myxedema, bronze disease and etc).

Hormones can be classified according to chemical structure, solubility, localization their receptors and influence on metabolism.

Classification of hormones by structure

Classification according to the effect on metabolism

Classification by place of synthesis

Hormonal signal

To regulate the activity of the cell with the help of hormones in the blood plasma, it is necessary to provide the cell with the ability to perceive and process this signal. This task is complicated by the fact that signal molecules ( neurotransmitters, hormones, eicosanoids) have different chemical nature, the response of cells to signals should be different in direction and adequate in magnitude.

In this regard, two main mechanisms of action of signaling molecules have evolved by receptor localization:

1. Membrane The receptor is located on the membrane. For these receptors, depending from method of transmitting a hormonal signal into the cell three types of membrane-bound receptors and correspondingly, three signal transmission mechanisms. Peptide and protein hormones, catecholamines, eicosanoids work according to this mechanism.

2. cytosolic The receptor is located in the cytosol.

The biochemistry of hormones, their chemical composition and functions are so complex that they constituted a separate branch of biological chemistry that emerged as a science at the beginning of the last century.

The importance of studying the mechanism of action of hormones

Almost all hormones are involved in the natural metabolism of the human body, while performing signaling and regulatory functions in any of its processes.

The mechanism by which biologically active chemicals produced in the cells of some organs of the body influence, through chemical reactions, the activity of other cells and organs is as complex as it is still not understood. The direct effect on the vital activity of the human body is undeniable, but knowledge about them is still not enough to properly manage them.

The structure of the already studied hormones showed that they have common properties, like other signaling molecules, and serve as a source of information transmission. Why some of them are collected in separate glands, while others circulate throughout the body, why one gland produces several types of different biologically active substances, which chemicals have an impact on starting a complex chain reaction mechanism, remains to be studied.

The moment when humanity learns to control, with reliable accuracy, the activity of hormones in a separate organism, a new page will open in its science and history.

Endocrine system of the human body

Only in the middle of the last century, hormones and vitamins were discovered, and the reactions that provide cells with energy potential were studied. The activity of the endocrine system, which synthesizes them and regulates the supply to the necessary zones of influence through circulating fluids, spreads throughout the human body.

Biology, which studies the glandular apparatus, carries out a general study of the structure, but in order to investigate the entire mechanism of interaction, including the freely transportable components of the activity of the endocrine glands, it took the joint efforts of the two sciences, on the verge of which biochemistry appeared. The study of the activity of hormones is of great importance, because it occupies an important place in the work of the body and the implementation of its vital functions.

During the life of the endocrine system:

• ensures coordination of organs and structures;
• participates in almost all chemical processes;
• stabilizes activity in relation to environmental conditions;
• controls development and growth;
• responsible for sexual differentiation;
• predominantly affects reproductive function;
• acts as one of the generators of human energy;
• forms psycho-emotional reactions and behavior.

All this is provided by a complex structure system consisting of a glandular apparatus and a diffuse part in the form of endocrine cells scattered throughout the body. The impact on the receptor of a certain stimulus leads to a signal sent by the central nervous system to, producing the corresponding message to the pituitary gland.

It transmits the command to tropic hormones, which it secretes for this purpose, and sends them to other glands. Those, in turn, produce their own agents, throwing them into the blood, where a chemical reaction occurs from interaction with certain cells.

The variety and variability of the provided functions and provoked reactions makes the endocrine system produce a significant range of chemically and biologically active substances of absolutely different types of effects, which, for ease of understanding, are described under the general collective term hormones.

Types of hormones and their functions

Enumeration of all produced by the human body is impossible, if only because not all of them have yet been identified and studied. However, substances known to man are enough for a very long list. The anterior pituitary produces:

• growth hormone (somatropin);
• melanin, responsible for the coloring pigment;
• thyroid-stimulating hormone, which regulates the activity of the thyroid gland;
• prolactin, which is responsible for the activity of the mammary glands and lactation.

Luteinizing and follicle-stimulating stimulate the sex glands, and therefore are classified as gonadotropins. The posterior pituitary gland produces:

• maintaining normal blood vessels;
• oxytocin, which causes uterine tone.

For many hormones, the main function is not the only one, and they additionally provide some processes.

The thyroid gland produces:

• thyroid hormones responsible for protein synthesis and nutrient breakdown. The exchange of carbohydrates, and the stimulation of natural metabolism is carried out with their participation and interaction with other chemical compounds;
• calcitonin, which was previously mistakenly considered a product of the activity of the parathyroid glands, is also produced in the thyroid gland, and is responsible for the level of calcium, and its hyperproduction, or lack, can cause serious pathologies.

Other hormone-producing organs

The adrenal medulla produces adrenaline, which ensures the body's response to danger, and, accordingly, the survival of the body itself. This is far from the only function of adrenaline, if we consider its interaction in chemical reactions with other biologically active substances.

Which the adrenal cortex produces are even more diverse:

• glucocorticoids affect metabolism and immune activity;
• mineralocorticoids maintain salt balance;
• androgens and estrogens act as sex steroids.

The testicles also produce, and the ovaries produce estrogens and progesterone. They prepare the uterus for fertilization.

The pancreas produces insulin and glucagon, which are responsible for the level of glucose in the blood, regulate through chemical reactions.

Gastrointestinal hormones - cholecystokinin, secretin and pancreozymin are the response of the gastrointestinal mucosa to specific stimulation, and ensure the digestion of food. Nerve cells synthesize a group of neurohormones, which are hormone-like substances. These are chemical compounds that stimulate or inhibit the activity of other cells.

The structure of some of them has been studied relatively well, and is used to regulate secretory mechanisms, in the form of finished drugs. Many hormones have been synthesized for this purpose, however, this is still an unplowed field for scientific activity, creative experiments, and future monographs by researchers.

Undoubtedly, further study of biochemical interactions, and the activity of the endocrine glands, will bring significant benefits for the cure of many hereditary diseases and pathologies.

Classification of hormones

To date, more than a hundred types of different hormones are known to science, and their diversity is a serious obstacle to any justified nomenclature classification. Four common hormonal typologies are compiled according to various classifying criteria, and none of them gives a sufficiently complete picture.

The most common classification is according to the place of synthesis, which refers the active substances to the producing gland. Despite the fact that it is very convenient for people who have nothing to do with the biochemistry of hormones as a science, the place of production does not fully give an idea of ​​the structure and nature of the biological component of the endocrine system.

Classification by chemical structure further confuses the matter, because it conventionally divides hormones into:

• steroids;
• protein-peptide substances;
• fatty acid derivatives;
• derivatives of amino acids.

But this is a conditional division, because the same chemical compounds perform different biological functions, and this makes it difficult to understand the mechanism of interactions.

Functional classification divides hormones into:

• effector (acting on a single target);
• tropic, responsible for the production of effector;
• releasing hormones that produce the synthesis of tropic and other pituitary hormones.

The main classification that can guide the understanding of the biochemistry of hormones is their division according to biological functions:

• lipid, carbohydrate and amino acid metabolism;
• calcium phosphate metabolism;
• metabolic exchange in hormone-producing cells;
• control and ensuring the activity of the reproductive function.

The chemical composition of biological substances, conditionally related to the terminological group under the general name of hormones, is distinguished by the peculiarity of the structure, which is due to the functions performed.

Structural structure and biosynthesis

The structure of hormones is a rather general topic, because many of them are formed by specialized cells and synthesized in various glands of the endocrine system. The structure of an individual hormone is determined both by the chemicals included in it and by the qualitative derivative of the reactions in which each individual reagent enters.

Most of the endocrine glands produce several chemically and biologically active substances, each of which has an individual structure, and functional responsibilities corresponding to this arrangement. Defects in the structure of the hormone can be the cause of systemic or hereditary diseases, and disrupt the implementation of metabolism, the activity of their receptors, destruct the mechanism of signal transmission to the target effect.

According to the chemical structure, hormones are divided into 3 main large groups:

• protein-peptide;
• mixed, not related to the first two.

The structure of protein hormones consists of amino acids that are linked by peptide bonds, and polypeptides are those that consist of less than 75 amino acids. Those that contain carbohydrate residues have their own name - glycoproteins.

Despite the similar structure, protein hormones are produced by various glands and have nothing in common in terms of the place of action, or its mechanism, and even in terms of size and molecular structure. Proteins include:

• releasing hormones;
• exchange;
• tissue;
• pituitary.

The structure of most protein hormones has been deciphered to date, and is produced in the form of synthetic agents used for therapeutic measures.

Steroids are produced only in the adrenal glands (cortex) and gonads, and contain a cyclopentanperhydrophenanthrene core. All steroids are derivatives of cholesterol, and the most famous of them are corticosteroids.

Many steroids are also synthesized in scientific laboratories. The third group, referred to in some sources as amines, is practically not amenable to any generalizing characteristics, because it contains both peptide groups and chemical intermediaries, such as nitric oxide, and long-chain fatty acids, and amine derivatives. The chemical composition of the mixed group, of course, cannot be reduced only to amines, because many chemical derivatives are conventionally included in it.

Mechanism of action and its features

The functions performed by hormones are so diverse that it is difficult even to imagine them to the uninitiated imagination:

• proliferative processes that they regulate in combined and sensitive tissues;
• development of secondary sexual characteristics;
• action of contractile muscles;
• intensity of metabolic metabolism, its course;
• adaptation, through chemical reactions in several systems at once, to changing environmental conditions;
• psycho-emotional arousal and the action of certain organs.

All this is carried out through certain mechanisms of interaction. Their interaction mechanisms, despite the different chemical structure of biologically and chemically active substances, have some similar features.

Hormones, whose biochemistry is aimed at carrying out several dozen types of reactions, interact with targets in the cell nucleus, or after attaching to the cell membrane. The interaction effect is provided only if the hormone has connected with the receptor and set its mechanism in motion. In some studies, the receptor is compared to a lock, the key of which is the hormone.

Only close interaction, turning the key, opens the closed, for the time being, lock. Important in this example is the correspondence of the hormone to the receptor.

The mechanism of interaction between hormones and other structures

The activity of synthesis, derepression, translation and transcription determines the intensity of metabolism. The action of hormones on the processes in which enzymes are involved is confirmed or blocked by cytostatics present in the cell.

Messenger RNA plays the role of a second mediator in ensuring enzymatic activity. Being derivatives of the endocrine glands that are secreted into the blood, they reach a very low concentration in the circulating fluid, and only the presence of specific receptors allows the target to capture the activator directed towards it.

Modern research has made it possible to establish the presence of specialized active substances that are responsible for the synthesis and reproduction of hormones necessary for the body, and the participation of hormones and neurohormones that act through nerve tissues to transmit nerve impulses occurs through different mechanisms.

Hormones interact with the motor end plate, while neurohormones pass through the CNS transport pathways, or through the pituitary portal system.

The hormonal mechanism of interaction is determined not only by the chemical structure of the active substance, but also by the method of its transportation, transport routes and the place where the hormone is synthesized.

The mechanism of action is a clear system of contact and influence on the cell membrane, or nucleus, due to biochemical reactions and information laid down at the genetic level.

Despite the significant difference in the structure of hormones, the mechanism of transmission, and the receptor itself, there are undoubtedly some common points in this process. Phosphorylation of proteins is an undoubted participant in signal transduction. Activation and its termination occurs with the help of special regulatory mechanisms, in which there is an undoubted moment of negative feedback.

Hormones are humoral regulators of body functions, and their main specific functions, and their task is to maintain its physiological balance, with the help of special chemical and biochemical reactions.

Biochemical Mechanisms of Signal Transmission and Effects on the Target Cell

The receptor protein has, on one of its domains, a site that is complementary in composition to the component of the signal molecule. The decisive factor in the process of interaction is the moment when a part of the signal molecule is confirmed in relative identity, and is accompanied by a moment similar to the formation of an enzyme-substrate community.

The mechanism of this reaction is not well understood, as are most receptors. The biochemistry of hormones knows only that at the moment of establishing complementarity between the receptor and part of the signal molecule, hydrophobic and electrostatic interactions are established.

At the moment when the receptor protein binds to the signal molecule complex, a biochemical reaction occurs, which triggers the whole mechanism, intracellular reactions, sometimes of a very specific nature.

Almost all endocrine disorders are based on the loss of the ability of the cellular receptor to recognize a signal, or to dock with signaling molecules. The cause of such disorders can be both genetic changes and the production of specific antibodies by the body, or insufficiency in the synthesis of receptors.

If the docking nevertheless took place successfully, then the interaction process begins, which, in the format studied to date, is differentiated into two types:

• lipophilic (the receptor is located inside the target cell);
• hydrophilic (location of the receptor in the outer membrane).

Which transmission mechanism is chosen in a particular case depends on the ability of the hormone molecule to penetrate the lipid layer of the target cell, or, if its size does not allow this, or it is polar, to communicate outside. The cell contains mediator substances that provide signal transmission and regulate the activity of enzyme groups inside the target.

To date, it is known about the participation in the mechanism of regulation of cyclic nucleotides, inositol triphosphate, protein kinase, calmodulin (calcium-binding protein), calcium ions, and some enzymes involved in protein phosphorylation.

The biological role of hormones in the body

Hormones play a huge role in ensuring the vital activity of the human body. This is evidenced by the fact that a violation of the production of a certain hormone by the endocrine glands can lead to the appearance of serious pathologies in a person, both congenital and acquired.

An excess or insufficient production of a hormone in the human body disrupts the normal, physiological process of its life, and creates a specific deterioration in the physical or psycho-emotional state. Parathyroid dysfunction creates problems with the musculoskeletal system, affects the skeletal system, disrupts the liver and kidneys.

In an amount different from the norm, it leads to mental disorders, calcification of the walls of blood vessels, or even internal organs. Headaches, muscle cramps, increased heart rate - all these are the consequences of a malfunction in the work of only one of the endocrine glands. Abnormal production of adrenal hormones:

• deprives a person of the opportunity to prepare for a stressful state;
• violates the metabolism of carbohydrates;
• leads to pathological pregnancy, its negative course, miscarriages;
• sexual infertility.

• regulate the process of digestion;
• insulin production;
• activate the process of splitting fats;
• increase blood glucose levels.

The pituitary gland affects the formation of luteinizing hormone, which affects reproductive function, is responsible for the normal development of the human body in all its periods.

All types of metabolism, growth and development, reproductive function, genetic information, the formation of the fetus in utero, the process of ovulation and conception, homeostasis, adaptation to the external environment - these are just some of the processes whose mechanism is entrusted to hormones.

External and general symptoms of hormonal failure

The biochemistry of hormones is a science allocated to independent study, and this is due to the important role that hormones play in the body. It cannot be overestimated, because the life cycle, working capacity, and psycho-emotional state depend on the normal hormonal background. Problems with the reproduction of hormones are easily diagnosed even without special tests, because a person begins to be accompanied by:

• headaches;
• violations of normal, full sleep;
• cyclical or spontaneous mood swings;
• unreasonable aggression and permanent irritability;
• bouts of sudden panic and fear.

All this is a direct consequence of a violation of hormonal production, and these alarming symptoms serve as a signal to see a doctor. The production and biochemistry of homones are complex processes that depend on many components, including hereditary factors. The study of these processes can provide significant assistance to modern medicine, which is why such close attention is paid to the biochemistry of hormones.

It has been proven that the number of human hormones is even more than a hundred and more studied to date, and the mechanisms of receptor communication and neurohumoral reactions still require the closest study.

Only after deciphering the analyzes, a specialist can begin to treat hormonal disorders and regulate the activity of the human body with the help of hormonal drugs, which have been developed and synthesized to a large extent by the biochemistry of hormones, a science created on the verge of biology, chemistry and medicine, and which is one of the most promising biochemical fields today.

Its further development can lead to the prevention of aging, preventing the appearance of genetic deformities, the cure of cancerous tumors, and the solution of many global problems of human health.

1. General properties of hormones Hormones are biologically active substances that are synthesized in small quantities in specialized cells of the endocrine system and are delivered through circulating fluids (for example, blood) to target cells, where they exert their regulatory effect.
Hormones, like other signaling molecules, share some common properties.
1) are released from the cells that produce them into the extracellular space;
2) are not structural components of cells and are not used as an energy source;
3) are able to specifically interact with cells that have receptors for a given hormone;
4) have a very high biological activity - effectively act on cells at very low concentrations (about 10 -6 -10 -11 mol/l).

2. Mechanisms of action of hormones Hormones affect target cells.
Target cells are cells that specifically interact with hormones using special receptor proteins. These receptor proteins are located on the outer membrane of the cell, or in the cytoplasm, or on the nuclear membrane and other organelles of the cell.
Biochemical mechanisms of signal transmission from the hormone to the target cell.
Any receptor protein consists of at least two domains (regions) that provide two functions:
1) hormone recognition;
2) transformation and transmission of the received signal to the cell.
How does the receptor protein recognize the hormone molecule with which it can interact?
One of the domains of the receptor protein contains a region complementary to some part of the signal molecule. The process of binding a receptor to a signal molecule is similar to the process of formation of an enzyme-substrate complex and can be determined by the value of the affinity constant.
Most of the receptors are not well understood because their isolation and purification are very difficult, and the content of each type of receptor in cells is very low. But it is known that hormones interact with their receptors in a physicochemical way. Electrostatic and hydrophobic interactions are formed between the hormone molecule and the receptor. When the receptor binds to the hormone, conformational changes in the receptor protein occur and the complex of the signal molecule with the receptor protein is activated. In the active state, it can cause specific intracellular reactions in response to the received signal. If the synthesis or ability of receptor proteins to bind to signal molecules is impaired, diseases arise - endocrine disorders. There are three types of such diseases.
1. Associated with insufficient synthesis of receptor proteins.
2. Associated with changes in the structure of the receptor - genetic defects.
3. Associated with the blocking of receptor proteins by antibodies.

Mechanisms of action of hormones on target cells Depending on the structure of the hormone, there are two types of interaction. If the hormone molecule is lipophilic (for example, steroid hormones), then it can penetrate the lipid layer of the outer membrane of target cells. If the molecule is large or polar, then its penetration into the cell is impossible. Therefore, for lipophilic hormones, the receptors are located inside the target cells, and for hydrophilic hormones, the receptors are located in the outer membrane.
In the case of hydrophilic molecules, an intracellular signal transduction mechanism operates to obtain a cellular response to a hormonal signal. This happens with the participation of substances, which are called second intermediaries. Hormone molecules are very diverse in shape, but "second messengers" are not.
The reliability of signal transmission provides a very high affinity of the hormone for its receptor protein.
What are the mediators that are involved in the intracellular transmission of humoral signals?
These are cyclic nucleotides (cAMP and cGMP), inositol triphosphate, calcium-binding protein - calmodulin, calcium ions, enzymes involved in the synthesis of cyclic nucleotides, as well as protein kinases - protein phosphorylation enzymes. All these substances are involved in the regulation of the activity of individual enzyme systems in target cells.
Let us analyze in more detail the mechanisms of action of hormones and intracellular mediators. There are two main ways of transmitting a signal to target cells from signaling molecules with a membrane mechanism of action:
1) adenylate cyclase (or guanylate cyclase) systems;
2) phosphoinositide mechanism.
adenylate cyclase system.
Main components: membrane protein receptor, G-protein, adenylate cyclase enzyme, guanosine triphosphate, protein kinases.
In addition, ATP is required for the normal functioning of the adenylate cyclase system.
The receptor protein, G-protein, next to which GTP and the enzyme (adenylate cyclase) are located, are built into the cell membrane.
Until the moment of hormone action, these components are in a dissociated state, and after the formation of the complex of the signal molecule with the receptor protein, changes in the conformation of the G protein occur. As a result, one of the G-protein subunits acquires the ability to bind to GTP.
The G-protein-GTP complex activates adenylate cyclase. Adenylate cyclase begins to actively convert ATP molecules into cAMP.
cAMP has the ability to activate special enzymes - protein kinases, which catalyze the phosphorylation reactions of various proteins with the participation of ATP. At the same time, phosphoric acid residues are included in the composition of protein molecules. The main result of this phosphorylation process is a change in the activity of the phosphorylated protein. In different cell types, proteins with different functional activities undergo phosphorylation as a result of activation of the adenylate cyclase system. For example, these can be enzymes, nuclear proteins, membrane proteins. As a result of the phosphorylation reaction, proteins can become functionally active or inactive.
Such processes will lead to changes in the rate of biochemical processes in the target cell.
The activation of the adenylate cyclase system lasts a very short time, because the G-protein, after binding to adenylate cyclase, begins to exhibit GTPase activity. After hydrolysis of GTP, the G-protein restores its conformation and ceases to activate adenylate cyclase. As a result, the cAMP formation reaction stops.
In addition to the participants in the adenylate cyclase system, some target cells have receptor proteins associated with G-proteins, which lead to the inhibition of adenylate cyclase. At the same time, the GTP-G-protein complex inhibits adenylate cyclase.
When cAMP formation stops, phosphorylation reactions in the cell do not stop immediately: as long as cAMP molecules continue to exist, the process of protein kinase activation will continue. In order to stop the action of cAMP, there is a special enzyme in cells - phosphodiesterase, which catalyzes the hydrolysis reaction of 3, 5 "-cyclo-AMP to AMP.
Some substances that have an inhibitory effect on phosphodiesterase (for example, the alkaloids caffeine, theophylline) help maintain and increase the concentration of cyclo-AMP in the cell. Under the influence of these substances in the body, the duration of activation of the adenylate cyclase system becomes longer, i.e., the action of the hormone increases.
In addition to the adenylate cyclase or guanylate cyclase systems, there is also a mechanism for information transfer inside the target cell with the participation of calcium ions and inositol triphosphate.
Inositol triphosphate is a substance that is a derivative of a complex lipid - inositol phosphatide. It is formed as a result of the action of a special enzyme - phospholipase "C", which is activated as a result of conformational changes in the intracellular domain of the membrane receptor protein.
This enzyme hydrolyzes the phosphoester bond in the phosphatidyl-inositol-4,5-bisphosphate molecule, resulting in the formation of diacylglycerol and inositol triphosphate.
It is known that the formation of diacylglycerol and inositol triphosphate leads to an increase in the concentration of ionized calcium inside the cell. This leads to the activation of many calcium-dependent proteins inside the cell, including the activation of various protein kinases. And here, as in the case of activation of the adenylate cyclase system, one of the stages of signal transmission inside the cell is protein phosphorylation, which leads to a physiological response of the cell to the action of the hormone.
A special calcium-binding protein, calmodulin, takes part in the work of the phosphoinositide signaling mechanism in the target cell. This is a low molecular weight protein (17 kDa), 30% consisting of negatively charged amino acids (Glu, Asp) and therefore capable of actively binding Ca +2. One calmodulin molecule has 4 calcium-binding sites. After interaction with Ca +2, conformational changes in the calmodulin molecule occur and the "Ca +2 -calmodulin" complex becomes able to regulate the activity (allosterically inhibit or activate) many enzymes - adenylate cyclase, phosphodiesterase, Ca +2, Mg +2 -ATPase and various protein kinases.
In different cells, when the "Ca + 2 -calmodulin" complex is exposed to isoenzymes of the same enzyme (for example, to adenylate cyclase of a different type), activation is observed in some cases, and inhibition of the cAMP formation reaction is observed in others. Such different effects occur because the allosteric centers of isoenzymes can include different amino acid radicals and their response to the action of the Ca + 2 -calmodulin complex will be different.
Thus, the role of "second messengers" for the transmission of signals from hormones in target cells can be:
1) cyclic nucleotides (c-AMP and c-GMP);
2) Ca ions;
3) complex "Sa-calmodulin";
4) diacylglycerol;
5) inositol triphosphate.
The mechanisms of information transfer from hormones inside target cells with the help of the above mediators have common features:
1) one of the stages of signal transmission is protein phosphorylation;
2) termination of activation occurs as a result of special mechanisms initiated by the participants in the processes themselves - there are negative feedback mechanisms.
Hormones are the main humoral regulators of the physiological functions of the body, and their properties, biosynthetic processes, and mechanisms of action are now well known.
The features by which hormones differ from other signaling molecules are as follows.
1. The synthesis of hormones occurs in special cells of the endocrine system. The synthesis of hormones is the main function of endocrine cells.
2. Hormones are secreted into the blood, more often into the venous, sometimes into the lymph. Other signaling molecules can reach target cells without being secreted into circulating fluids.
3. Telecrine effect (or distant action) - hormones act on target cells at a great distance from the place of synthesis.
Hormones are highly specific substances with respect to target cells and have a very high biological activity.
3. Chemical structure of hormones The structure of hormones is different. Currently, about 160 different hormones from different multicellular organisms have been described and isolated. According to the chemical structure, hormones can be classified into three classes:
1) protein-peptide hormones;
2) derivatives of amino acids;
3) steroid hormones.
The first class includes the hormones of the hypothalamus and pituitary gland (peptides and some proteins are synthesized in these glands), as well as the hormones of the pancreas and parathyroid glands and one of the thyroid hormones.
The second class includes amines, which are synthesized in the adrenal medulla and in the epiphysis, as well as iodine-containing thyroid hormones.
The third class is steroid hormones, which are synthesized in the adrenal cortex and in the gonads. By the number of carbon atoms, steroids differ from each other:
C 21 - hormones of the adrenal cortex and progesterone;
C 19 - male sex hormones - androgens and testosterone;
From 18 - female sex hormones - estrogens.
Common to all steroids is the presence of a sterane core.
4. Mechanisms of action of the endocrine system Endocrine system - a set of endocrine glands and some specialized endocrine cells in tissues for which the endocrine function is not the only one (for example, the pancreas has not only endocrine, but also exocrine functions). Any hormone is one of its participants and controls certain metabolic reactions. At the same time, there are levels of regulation within the endocrine system - some glands have the ability to control others.

General scheme for the implementation of endocrine functions in the body This scheme includes the highest levels of regulation in the endocrine system - the hypothalamus and pituitary gland, which produce hormones that themselves affect the processes of synthesis and secretion of hormones of other endocrine cells.
The same scheme shows that the rate of synthesis and secretion of hormones can also change under the influence of hormones from other glands or as a result of stimulation by non-hormonal metabolites.
We also see the presence of negative feedbacks (-) - inhibition of synthesis and (or) secretion after the elimination of the primary factor that caused the acceleration of hormone production.
As a result, the content of the hormone in the blood is maintained at a certain level, which depends on the functional state of the organism.
In addition, the body usually creates a small reserve of individual hormones in the blood (this is not visible in the diagram). The existence of such a reserve is possible because many hormones in the blood are in a state associated with special transport proteins. For example, thyroxine is associated with thyroxine-binding globulin, and glucocorticosteroids are associated with the protein transcortin. Two forms of such hormones - associated with transport proteins and free - are in the blood in a state of dynamic equilibrium.
This means that when the free forms of such hormones are destroyed, the bound form will dissociate and the concentration of the hormone in the blood will be maintained at a relatively constant level. Thus, a complex of a hormone with a transport protein can be considered as a reserve of this hormone in the body.

Effects that are observed in target cells under the influence of hormones It is very important that hormones do not cause any new metabolic reactions in the target cell. They only form a complex with the receptor protein. As a result of the transmission of a hormonal signal in the target cell, cellular reactions are switched on or off, providing a cellular response.
In this case, the following main effects can be observed in the target cell:
1) change in the rate of biosynthesis of individual proteins (including enzyme proteins);
2) a change in the activity of already existing enzymes (for example, as a result of phosphorylation - as has already been shown using the adenylate cyclase system as an example;
3) a change in the permeability of membranes in target cells for individual substances or ions (for example, for Ca +2).
It has already been said about the mechanisms of hormone recognition - the hormone interacts with the target cell only in the presence of a special receptor protein. The binding of the hormone to the receptor depends on the physicochemical parameters of the medium - on pH and the concentration of various ions.
Of particular importance is the number of receptor protein molecules on the outer membrane or inside the target cell. It changes depending on the physiological state of the body, with diseases or under the influence of drugs. And this means that under different conditions the reaction of the target cell to the action of the hormone will be different.
Different hormones have different physicochemical properties and the location of receptors for certain hormones depends on this. It is customary to distinguish between two mechanisms of interaction of hormones with target cells:
1) membrane mechanism - when the hormone binds to the receptor on the surface of the outer membrane of the target cell;
2) intracellular mechanism - when the receptor for the hormone is located inside the cell, i.e. in the cytoplasm or on intracellular membranes.
Hormones with a membrane mechanism of action:
1) all protein and peptide hormones, as well as amines (adrenaline, norepinephrine).
The intracellular mechanism of action is:
1) steroid hormones and derivatives of amino acids - thyroxine and triiodothyronine.
Transmission of a hormonal signal to cell structures occurs according to one of the mechanisms. For example, through the adenylate cyclase system or with the participation of Ca +2 and phosphoinositides. This is true for all hormones with a membrane mechanism of action. But steroid hormones with an intracellular mechanism of action, which usually regulate the rate of protein biosynthesis and have a receptor on the surface of the nucleus of the target cell, do not need additional messengers in the cell.

Features of the structure of protein receptors for steroids The most studied is the receptor for the hormones of the adrenal cortex - glucocorticosteroids (GCS). This protein has three functional regions:
1 - for binding to the hormone (C-terminal);
2 - for binding to DNA (central);
3 - antigenic site, simultaneously able to modulate the function of the promoter in the transcription process (N-terminal).
The functions of each site of such a receptor are clear from their names, it is obvious that such a structure of the steroid receptor allows them to influence the rate of transcription in the cell. This is confirmed by the fact that under the action of steroid hormones, the biosynthesis of certain proteins in the cell is selectively stimulated (or inhibited). In this case, acceleration (or deceleration) of mRNA formation is observed. As a result, the number of synthesized molecules of certain proteins (often enzymes) changes and the rate of metabolic processes changes.

5. Biosynthesis and secretion of hormones of various structures Protein-peptide hormones. In the process of formation of protein and peptide hormones in the cells of the endocrine glands, a polypeptide is formed that does not have hormonal activity. But such a molecule in its composition has a fragment (s) containing (e) the amino acid sequence of this hormone. Such a protein molecule is called a pre-pro-hormone and has (usually at the N-terminus) a structure called a leader or signal sequence (pre-). This structure is represented by hydrophobic radicals and is needed for the passage of this molecule from the ribosomes through the lipid layers of the membranes into the cisterns of the endoplasmic reticulum (ER). At the same time, during the passage of the molecule through the membrane, as a result of limited proteolysis, the leader (pre-) sequence is cleaved off and a prohormone appears inside the ER. Then, through the EPR system, the prohormone is transported to the Golgi complex, and here the maturation of the hormone ends. Again, as a result of hydrolysis under the action of specific proteinases, the remaining (N-terminal) fragment (pro-site) is cleaved off. The formed hormone molecule with specific biological activity enters the secretory vesicles and accumulates until the moment of secretion.
During the synthesis of hormones from among the complex proteins of glycoproteins (for example, follicle-stimulating (FSH) or thyroid-stimulating (TSH) hormones of the pituitary gland), in the process of maturation, the carbohydrate component is included in the structure of the hormone.
Extraribosomal synthesis can also occur. This is how the tripeptide thyroliberin (hormone of the hypothalamus) is synthesized.
Hormones are derivatives of amino acids. From tyrosine, the hormones of the adrenal medulla adrenaline and norepinephrine, as well as iodine-containing thyroid hormones, are synthesized. During the synthesis of adrenaline and norepinephrine, tyrosine undergoes hydroxylation, decarboxylation, and methylation with the participation of the active form of the amino acid methionine.
The thyroid gland synthesizes the iodine-containing hormones triiodothyronine and thyroxine (tetraiodothyronine). During the synthesis, iodination of the phenolic group of tyrosine occurs. Of particular interest is the metabolism of iodine in the thyroid gland. The glycoprotein thyroglobulin (TG) molecule has a molecular weight of more than 650 kDa. At the same time, in the composition of the TG molecule, about 10% of the mass is carbohydrates and up to 1% is iodine. It depends on the amount of iodine in the food. The TG polypeptide contains 115 tyrosine residues, which are iodinated by iodine oxidized with the help of a special enzyme - thyroperoxidase. This reaction is called iodine organification and occurs in the thyroid follicles. As a result, mono- and di-iodotyrosine are formed from tyrosine residues. Of these, approximately 30% of the residues can be converted into tri- and tetra-iodothyronines as a result of condensation. Condensation and iodination proceed with the participation of the same enzyme, thyroperoxidase. Further maturation of thyroid hormones occurs in glandular cells - TG is absorbed by cells by endocytosis and a secondary lysosome is formed as a result of the fusion of the lysosome with the absorbed TG protein.
Proteolytic enzymes of lysosomes provide hydrolysis of TG and the formation of T 3 and T 4 , which are released into the extracellular space. And mono- and diiodotyrosine are deiodinated using a special deiodinase enzyme and iodine can be reorganized. For the synthesis of thyroid hormones, the mechanism of inhibition of secretion by the type of negative feedback is characteristic (T 3 and T 4 inhibit the release of TSH).

Steroid hormones Steroid hormones are synthesized from cholesterol (27 carbon atoms), and cholesterol is synthesized from acetyl-CoA.
Cholesterol is converted into steroid hormones as a result of the following reactions:
1) elimination of the side radical;
2) the formation of additional side radicals as a result of the hydroxylation reaction with the help of special enzymes of monooxygenases (hydroxylases) - most often in the 11th, 17th, and 21st positions (sometimes in the 18th). At the first stage of the synthesis of steroid hormones, precursors (pregnenolone and progesterone) are first formed, and then other hormones (cortisol, aldosterone, sex hormones). Aldosterone, mineralocorticoids can be formed from corticosteroids.

Secretion of hormones Regulated by the central nervous system. Synthesized hormones accumulate in secretory granules. Under the action of nerve impulses or under the influence of signals from other endocrine glands (tropic hormones), as a result of exocytosis, degranulation occurs and the hormone is released into the blood.
The mechanisms of regulation as a whole were presented in the scheme of the mechanism for the implementation of the endocrine function.

6. Transport of hormones The transport of hormones is determined by their solubility. Hormones of a hydrophilic nature (for example, protein-peptide hormones) are usually transported in the blood in a free form. Steroid hormones, iodine-containing thyroid hormones are transported in the form of complexes with blood plasma proteins. These can be specific transport proteins (transport low molecular weight globulins, thyroxin-binding protein; transporting corticosteroids protein transcortin) and non-specific transport (albumins).
It has already been said that the concentration of hormones in the bloodstream is very low. And it can change in accordance with the physiological state of the body. With a decrease in the content of individual hormones, a condition develops, characterized as hypofunction of the corresponding gland. Conversely, an increase in the content of the hormone is a hyperfunction.
The constancy of the concentration of hormones in the blood is also ensured by the processes of catabolism of hormones.
7. Hormone catabolism Protein-peptide hormones undergo proteolysis, break down to individual amino acids. These amino acids further enter into the reactions of deamination, decarboxylation, transamination and decompose to the final products: NH 3, CO 2 and H 2 O.
Hormones undergo oxidative deamination and further oxidation to CO 2 and H 2 O. Steroid hormones break down differently. There are no enzyme systems in the body that would ensure their breakdown.
Basically, the side radicals are modified. Additional hydroxyl groups are introduced. Hormones become more hydrophilic. Molecules are formed that are the structure of a sterane, in which the keto group is located in the 17th position. In this form, the products of catabolism of steroid sex hormones are excreted in the urine and are called 17-ketosteroids. Determination of their quantity in urine and blood shows the content of sex hormones in the body.

Federal State Budgetary Educational Institution of Higher Education USMU of the Ministry of Health of Russia
Department of Biochemistry
Discipline: Biochemistry
LECTURE #14
regulatory systems of the body.
Biochemistry of the endocrine system
Lecturer: Gavrilov I.V.
Faculties: medical and preventive,
pediatric
Course: 2
Yekaterinburg, 2016

LECTURE PLAN

1. Regulatory systems of the body.
Levels and principles of organization.
2. Hormones. Concept definition. Peculiarities
actions.
3. Classification of hormones: according to the place of synthesis and
chemical nature, properties.
4. The main representatives of hormones
5. Stages of hormone metabolism.

Basic properties of living organisms
1. The unity of the chemical composition.
2. Metabolism and energy
3. Living systems are open systems: they use external
energy sources in the form of food, light, etc.
4. Irritability - the ability of living systems to respond
on external or internal influences (changes).
5. Excitability - the ability of living systems to respond to
stimulus action.
6. Movement, the ability to move.
7. Reproduction, ensuring the continuity of life in
generations
8. Heredity
9. Variability
10. Living systems are self-governing,
self-regulating, self-organizing systems

Living organisms are able to maintain
the constancy of the internal environment - homeostasis.
Disruption of homeostasis leads to disease or
of death.
Indices of homeostasis in mammals
pH regulation
Regulation of water-salt metabolism.
Regulation of the concentration of substances in the body
Metabolic regulation
Regulation of the rate of energy metabolism
Body temperature regulation.

Homeostasis in the body is maintained by regulating the rate of enzymatic reactions, by changing: I). Availability of substrate molecules

Homeostasis in the body is maintained by
regulation of the rate of enzymatic reactions, for
change account:
I). Availability of substrate and coenzyme molecules;
II). Catalytic activity of enzyme molecules;
III). The number of enzyme molecules.
E*
S
S
coenzyme
Vitamin
Cell
P
P

In multicellular organisms in maintaining
Homeostasis involves 3 systems:
one). nervous
2). humoral
3). immune
Regulatory systems function with the participation
signal molecules.
Signal molecules are organic
substances that carry information.
For signal transmission:
BUT). The CNS uses neurotransmitters (regulates physiological
functions and functioning of the endocrine system)
B). The humoral system uses hormones (regulates
metabolic and physiological processes, proliferation,
differentiation of cells and tissues
IN). The immune system uses cytokines (to protect the body from
external and internal pathogenic factors, regulates immune
and inflammatory reactions, proliferation, differentiation
cells, the functioning of the endocrine system)

Signal molecules
Non-specific factors: pH, t
Specific Factors: Signal Molecules
Enzyme
substrate
Product

External and internal factors
CNS
Regulatory systems form
3 hierarchical levels
I.
neurotransmitters
Hypothalamus
releasing hormones
liberins statins
Pituitary
II.
tropic hormones
Endocrine glands
hormones
Target tissues
III.
S
E
P
The first level is the CNS. Nerve cells
receive signals from external and internal
environment, transform them into the form of a nervous
momentum
And
transmit
across
synapses,
using
neurotransmitters,
which
cause
changes
metabolism
in
effector cells.
The second level is the endocrine system.
Includes
hypothalamus,
pituitary,
peripheral endocrine glands, and
separate
cells
(APUD
system),
synthesizing
under
influence
appropriate stimulus hormones that
through the blood act on target tissues.
The third level is intracellular. On the
metabolic processes in the cell
substrates and metabolic products, as well as
tissue hormones (autocrine).

Principles of organization of the neuroendocrine system
The neuroendocrine system is based on
principle of direct, inverse, positive and negative
connections.
1. The principle of direct positive connection - activation
the current link of the system leads to the activation of the next
link of the system, signal propagation towards target cells and the occurrence of metabolic or
physiological changes.
2. The principle of a direct negative connection - activation
the current link of the system leads to the suppression of the next
link of the system and the termination of signal propagation in
towards the target cells.
3. Negative feedback principle - activation
the current link of the system causes the suppression of the previous
link of the system and the termination of its stimulating effect on
current system.
Principles of direct positive and negative feedback
are the basis for maintaining homeostasis.

10.

4. The principle of positive feedback -
activation of the current link of the system causes
stimulation of the previous link in the system. The foundation
cyclic processes.
HYPOTHALAMUS
Gonadotropin-releasing hormone
PITUITARY
FSH
FOLLICLE
Estradiol

11.

Hormones
The term hormone (hormao - excite, awaken) was introduced in 1905
Bayliss and Starling to express secretin activity.
Hormones are organic signaling molecules
wireless system action.
1. Synthesized in the endocrine glands,
2. transported by blood
3. act on target tissues (thyroid hormones
glands, adrenal glands, pancreas, etc.).
In total, more than 100 hormones are known.

12.

The target tissue is the tissue in which the hormone causes
specific biochemical or
physiological response.
Target tissue cells for interaction with
special receptors are synthesized by the hormone
the number and type of which determines
intensity and nature of the response.
There are about 200 types of differentiated
cells, only some of them produce
hormones, but all are targets for
the action of hormones.

13.

Features of the action of hormones:
1. Act in small quantities (10-6-10-12 mmol/l);
2. There is absolute or high specificity in
action of hormones.
3. Only information is transferred. Not used in
energy and construction purposes;
4. Act indirectly through cascade systems,
(adenylate cyclase, inositol triphosphate, etc.)
systems) interacting with receptors;
5. Regulate
activity,
number
proteins
(enzymes), transport of substances through the membrane;
6. Depend on the central nervous system;
7. Non-threshold principle. Even 1 molecule of the hormone
able to have an effect
8. Final effect - the result of the action of the set
hormones.

14.

Cascade systems
Hormones regulate the amount and catalytic
enzyme activity not directly, but
indirectly through cascade systems
Hormones
Cascade systems
Enzymes
x 1000000
Cascade systems:
1. Repeatedly increase the hormone signal (increase
the amount or catalytic activity of the enzyme) so
that 1 molecule of a hormone can cause a change
metabolism in the cell
2. Provide signal penetration into the cell
(water-soluble hormones do not enter the cell on their own
penetrate)

15.

cascade systems consist of:
1. receptors;
2. regulatory proteins (G-proteins, IRS, Shc, STAT, etc.).
3. secondary intermediaries (messenger - messenger)
(Ca2+, cAMP, cGMP, DAG, ITP);
4. enzymes (adenylate cyclase, phospholipase C,
phosphodiesterase, protein kinases A, C, G,
phosphoprotein phosphatase);
Types of cascade systems:
1. adenylate cyclase,
2. guanylate cyclase,
3. inositol triphosphate,
4. RAS, etc.),

16.

Hormones have both systemic and local
action:
1. Endocrine (systemic) action of hormones
(endocrine effect) is realized when they
transported by the blood and act on the organs and
tissues throughout the body. characteristic of true
hormones.
2. The local action of hormones is realized when they
operate
on the
cells,
in
which
were
synthesized (autocrine effect), or on
neighboring
cells
(paracrine
the effect).
Characteristic for true and tissue hormones.

17. Classification of hormones

A. By chemical structure:
1.Peptide hormones
releasing hormones of the hypothalamus
pituitary hormones
Parathormone
Insulin
Glucagon
Calcitonin
2. Steroid hormones
sex hormones
Corticoids
calcitriol
3. Derivatives of amino acids (tyrosine)
Thyroid hormones
Catecholamines
4. Eicosanoids - derivatives of arachidonic acid
(hormone-like substances)
Leukotrienes, Thromboxanes, Prostaglandins, Prostacyclins

18.

B. At the place of synthesis:
1. Hormones of the hypothalamus
2. Pituitary hormones
3. Pancreatic hormones
4. Parathyroid hormones
5. Thyroid hormones
6. Adrenal hormones
7. Hormones of the gonads
8. Gastrointestinal hormones
9. etc

19.

B. According to biological functions:
Regulated processes
Hormones
Metabolism of carbohydrates, lipids, insulin, glucagon, adrenaline,
amino acids
thyroxine, somatotropin
Water-salt exchange
cortisol,
Aldosterone, an antidiuretic hormone
Calcium and phosphate metabolism Parathyroid hormone, calcitonin, calcitriol
reproductive function
Synthesis
hormones
glands
And
Estradiol
testosterone,
gonadotropic hormones
secretion of tropic hormones from the pituitary gland,
endocrine statins of the hypothalamus
progesterone,
liberals
And
Change in metabolism to Eicosanoids, histamine, secretin, gastrin,
cells that synthesize somatostatin, vasoactive intestinal
hormone
peptide (VIP), cytokines

20. Hormones of the hypothalamus and pituitary gland

Major Hormones
Hormones of the hypothalamus and pituitary gland

21. Hormones of the Hypothalamus

Releasing hormones - maintain basal levels
and physiological peaks in the production of tropic hormones
pituitary gland and normal functioning
peripheral endocrine glands
Release factors
(hormones)
Liberians
Secretion activation
tropic hormones
Statins
secretion inhibition
tropic hormones

22.

Thyrotropin releasing hormone (TRH)
Tripeptide: PYRO-GLU-GIS-PRO-NH2
CO NH CH CO N
CH2
C
O
C
O
N
H
Stimulates the secretion of: Thyroid-stimulating hormone (TSH)
Prolactin
Somatotropin
NH2

23.

Gonadotropin releasing hormone (GRH)
Decapeptide:
PIRO-GLU-GIS-TRP-SERT-TYR-GLY-LEY-ARG-PRO-GLY-NH2
Stimulates secretion of: follicle-stimulating hormone
luteinizing hormone
Corticotropin releasing hormone (CRH)
Peptide 41 amino acid residue.
Stimulates secretion of: vasopressin
oxytocin
catecholamines
angiotensin-2

24.

Somatostanin releasing hormone (SHR)
Peptide 44 amino acid residues
inhibits the secretion of growth hormone
Somatotropin inhibitory hormone (SIH)
Tetradecopeptide (14 amino acid residues)
ALA-GLY-CIS-LYS-ASN-PHEH-PHEN-TRP-LYS-TRE-PHEH-TRE-SERP-CIS-NH2
S
S
Inhibit secretion of: growth hormone, insulin, glucagon.
Melanotropin releasing hormone
Melanotropin inhibitory hormone
Regulate the secretion of melanostimulating hormone

25.

pituitary hormones
Anterior pituitary gland
1 Somatomammotropins:
- a growth hormone
- prolactin
- chorionic somatotropin
2 Peptides:
- ACTH
- -lipotropin
- enkephalins
- endorphins
- melanostimulating hormone
POMK
3 Glycoprotein hormones: - thyrotropin
- luteinizing hormone
- follicle-stimulating hormone
- human chorionic gonadotropin

26.

Posterior pituitary gland
Vasopressin
N-CIS-TYR-FEN-GLN-ASN-CIS-PRO-ARG-GLY-CO-NH2
S
S
Synthesized by the supraoptic nucleus of the hypothalamus
Concentration in blood 0-12 pg/ml
Ejection is regulated by blood loss
Functions: 1) Stimulates water reabsorption
2) stimulates gluconeogenesis, glycogenolysis
3) constricts blood vessels
4) is a component of the stress response

27.

Oxytocin
N-CIS-TYR-ILE-GLN-ASN-CIS-PRO-LEU-GLY-CO-NH2
S
S
Synthesized by the paraventricular nucleus of the hypothalamus
Functions: 1) stimulates the secretion of milk by the mammary glands
2) stimulates uterine contractions
3) releasing factor for the release of prolactin

28. Major steroid hormones

Hormones of peripheral glands
Major steroid hormones
CH2OH
C O
CH3
C O
HO
O
O
Progesterone
HO
Corticosterone
CH2OH
C O
Oh
OCH2OH
HC C O
HO
O
O
cortisol
Aldosterone

29.

Testosterone
Estradiol

30.

ovaries
testicles
Placenta
adrenal glands

31. Amino acid derivatives

Tyrosine
Triiodothyronine
Adrenalin
thyroxine

32.

Gastrointestinal
(intestinal) hormones
4. Other peptides
1. Gastrin-cholecystokinin family
-somatostatin
-gastrin
- neurotensin
- cholecystokinin
-motilin
2. The secretin-glucagon family
-substance P
- secretin
- pancreostatin
-glucagon
- gastro-inhibiting pectide
- vasoactive intestinal peptide
-peptide histidine-isoleucine
3. RR family
- pancreatic polypeptide
-peptide YY
-neuropeptide Y

33. Stages of hormone metabolism

1.
2.
3.
4.
5.
6.
7.
Synthesis
Activation
Storage
Secretion
Transport
Action
inactivation
The pathways of hormone metabolism depend on their nature.

34. Metabolism of peptide hormones

35. Synthesis, activation, storage and secretion of peptide hormones

DNA
Exon
Intron
Exon
Intron
transcription
Pre mRNA
processing
mRNA
Ribosomes
Signal
peptide
SER
cytoplasmic membrane
Core
broadcast
preprohormone
Complex
golgi
proteolysis,
glycosylation
prohormone
active hormone
Secretory
bubbles
Signal
molecules
ATP

36.

37.

The transport of peptide hormones is carried out in
free form (water soluble) and in combination with
proteins.
Mechanism of action. Peptide hormones
interact with membrane receptors and
system of intracellular mediators regulate
enzyme activity, which affects the intensity
metabolism in target tissues.
To a lesser extent, peptide hormones regulate
protein biosynthesis.
The mechanism of action of hormones (receptors, mediators)
discussed in the enzymes section.
Inactivation. Hormones are inactivated by hydrolysis to
AA in target tissues, liver, kidneys, etc. Time
half-life of insulin, glucagon T½ = 3-5 min, in STH
T½= 50 min.

38.

The mechanism of action of protein hormones
(adenylate cyclase system)
Protein
hormone
ATP
protein kinase
AC
cAMP
Protein kinase (act)
Phosphorylation
E (inactive)
E (act)
substrate
Product

39. Metabolism of steroid hormones

40.

1. The synthesis of hormones comes from cholesterol in
smooth ER and mitochondria of the adrenal cortex,
gonads, skin, liver, kidneys. Steroid conversion
consists in the cleavage of the aliphatic side chain,
hydroxylation, dehydrogenation, isomerization, or
in the aromatization of the ring.
2. Activation. Steroid hormones are often produced
already active.
3. Storage. Synthesized hormones accumulate
in the cytoplasm in combination with special proteins.
4. The secretion of steroid hormones occurs passively.
Hormones move from cytoplasmic proteins to
cell membrane, from where they are taken by transport
blood proteins.
5. Transport. Steroid hormones, tk. they
water insoluble, predominantly transported in the blood
in complex with transport proteins (albumins).

41. Synthesis of corticoid hormones

Progesterone
17ά
oxyprogesterone
21
deoxycortisol
Pregnenolone
Cholesterol
17ά
17ά ,21
11
oxypregnenolone dioxypregnenolone deoxycortisol
11β
oxypregnenolone
21
oxypregnenolone
cortisol
cortisone
11β
oxyprogesterone
11β,21
dioxypregnenolone
corticosterone
deoxycortico
sterone
18
oxypregnenolone
18
oxidesoxycorthy
bonfire
18
oxycorticosterone
aldosterone

42.

The mechanism of action of steroid hormones
DNA
cytoreceptor
G
R
G R
ions
Glucose
AK
R
I - RNA
Activated
hormone - receptor
complex
protein synthesis

43.

Inactivation. Steroid hormones are inactivated
So
same
how
And
xenobiotics
reactions
hydroxylation and conjugation in the liver and tissues
targets. Inactivated derivatives are displayed
from the body with urine and bile. Half-life in
blood is usually more peptide hormones. At
cortisol T½ = 1.5-2 hours.

44. METABOLISM OF CATECHOLAMINES Sympathetic-adrenal axis

1. Synthesis. Synthesis of catecholamines occurs in the cytoplasm and granules
adrenal medulla cells. Catecholamines are immediately formed in
active form. Norepinephrine is produced mainly in the organs
innervated by sympathetic nerves (80% of the total).
norepinephrine
Oh
Oh
O2 H2O
Oh
Fe2+
CH 2
HC
COOH
Tyr
Oh
OH O2 H2O
HC
Cu2+
CH 2
NH2
COOH
H2C
NH2
dopamine
Oh
Oh
Oh
Oh
vit. FROM
B6
CH 2
NH2
CO2
3SAM 3SAG
HC
IS HE
HC
H2C
NH2
H2C
norepinephrine
DOPA

IS HE
N+H-CH
(CH 3)33
adrenalin
methyltransferase

45.

2. Storage of catecholamines occurs in secretory granules.
Catecholamines enter the granules via ATP-dependent transport and
stored in them in combination with ATP in a ratio of 4:1 (hormone-ATP).
3. The secretion of hormones from the granules occurs by exocytosis. IN
unlike sympathetic nerves, cells of the adrenal medulla
devoid of a reuptake mechanism for released catecholamines.
4. Transport. In blood plasma, catecholamines form an unstable
complex with albumin. Adrenaline is transported mainly to
liver and skeletal muscles. Norepinephrine only in minor
reaches the peripheral tissues.
5. Action of hormones. Catecholamines regulate activity
enzymes, they act through cytoplasmic receptors.
Adrenaline through α-adrenergic and β-adrenergic receptors,
norepinephrine - through α-adrenergic receptors. Through β-receptors
the adenylate cyclase system is activated, through α2 receptors
is inhibited. Through α1 receptors, inositol triphosphate is activated
system. The effects of catecholamines are numerous and affect
almost all types of exchange.
7. Inactivation. The bulk of catecholamines
metabolized in various tissues with the participation of specific
enzymes.

46. ​​METABOLISM OF THYROID HORMONES Hypothalamic-pituitary-thyroid axis

Synthesis of thyroid hormones (iodothyronines: 3,5,3 "triiodothyronine
(triiodothyronine,
T3)
And
3,5,3", 5" tetraiodothyronine (T4, thyroxine)) occurs in cells and
thyroid colloid.
1. Protein is synthesized in thyrocytes (in follicles)
thyroglobulin. (+ TSH) This is a glycoprotein with a mass of 660 kD,
containing 115 tyrosine residues, 8-10% of its mass
belong to carbohydrates.
At first
on the
ribosomes
EPR
synthesized
prethyreoglobulin, which in the EPR forms a secondary and
tertiary structure, glycosylated and converted to
thyroglobulin. From the EPR, thyroglobulin enters the apparatus
Golgi, where it is incorporated into secretory granules and
secreted into the extracellular colloid.

47.

2. Transport of iodine into the colloid of the thyroid gland. Iodine in
in the form of organic and inorganic compounds enters
in the gastrointestinal tract with food and drinking water. daily requirement for
iodine 150-200 mcg. 25-30% of this amount of iodides
taken up by the thyroid gland. I- enters the cells
thyroid gland by active transport with the participation
iodide-carrying protein symport with Na+. Further, I passively enters the colloid along the gradient.
3. Oxidation of iodine and iodination of tyrosine. in a colloid
with the participation of heme-containing thyroperoxidase and H2O2, I is oxidized to I+, which iodinates tyrosine residues into
thyroglobulin with the formation of monoiodotyrosines (MIT)
and diiodotyrosines (DIT).
4. Condensation of MIT and DIT. Two DIT molecules
condense to form T4 iodothyronine, and MIT and
DIT - with the formation of T3 iodothyronine.

48.

49.

2. Storage. As part of iodothyroglobulin, thyroid
hormones are accumulated and stored in the colloid.
3. Secretion. Iodhyroglobulin is phagocytosed from
colloid into the follicular cell and hydrolyzed into
lysosomes with the release of T3 and T4 and tyrosine and other AAs.
Similar to steroid hormones, water insoluble
thyroid hormones in the cytoplasm bind to
special proteins that carry them into the composition
cell membrane. Normal thyroid gland
secretes 80-100 micrograms of T4 and 5 micrograms of T3 per day.
4. Transport. The main part of thyroid hormones
transported in the blood in protein-bound form.
The main transport protein of iodothyronines, as well as
the form of their deposition is thyroxin-binding
globulin (TSG). It has a high affinity for T3 and T4 and
under normal conditions binds almost the entire amount
these hormones. Only 0.03% T4 and 0.3% T3 are in the blood
in free form.

50.

BIOLOGICAL EFFECTS
Triiodothyronine and thyroxine bind to the nuclear receptor of target cells
1. For the main exchange. are uncouplers of biological oxidation inhibit the formation of ATP. The level of ATP in cells decreases and the body
responds with an increase in O2 consumption, the basal metabolism increases.
2. For carbohydrate metabolism:
- increases the absorption of glucose in the gastrointestinal tract.
- stimulates glycolysis, pentose phosphate oxidation pathway.
- enhances the breakdown of glycogen
- increases the activity of glucose-6-phosphatase and other enzymes
3. For protein exchange:
- induce synthesis (like steroids)
- provide a positive nitrogen balance
- stimulate the transport of amino acids
4. For lipid metabolism:
- stimulate lipolysis
- enhance fatty acid oxidation
- inhibit cholesterol biosynthesis
_

51.

inactivation
iodothyronines
carried out
in
peripheral tissues as a result of T4 deiodination to
"reverse" T3 by 5, complete deiodination,
deamination
or
decarboxylation.
Iodized catabolism products of iodothyronines
conjugated in the liver with glucuronic or sulfuric
acids, secreted with bile, in the intestine again
absorbed, deiodinated in the kidneys and excreted
urine. For T4 T½ = 7 days, for T3 T½ = 1-1.5 days.

52. LECTURE No. 15

GBOU VPO USMU of the Ministry of Health of the Russian Federation
Department of Biochemistry
Discipline: Biochemistry
LECTURE #15
Hormones and adaptation
Lecturer: Gavrilov I.V.
Faculty: medical and preventive,
Course: 2
Yekaterinburg, 2016

53. Lecture plan

1. Stress - as a general adaptive
syndrome
2. Stages of stress reactions: characteristics
metabolic and biochemical
changes.
3. The role of the pituitary-adrenal
system, catecholamines, growth hormone, insulin,
thyroid hormones, sex
hormones in the implementation of adaptive
processes in the body.

54.

Adaptation (from lat. adaptatio) adaptation of the body to conditions
existence.
The purpose of adaptation is to eliminate or
mitigation of harmful effects
environmental factors:
1. biological,
2. physical,
3. chemical,
4. social.

55. Adaptation

NON-SPECIFIC
Provides
activation
protective systems
organism, for
adaptation to any
environmental factor.
SPECIFIC
Causes changes in
body,
aimed at
weakening or
action elimination
specific
unfavorable
factor a.

56. 3 types of adaptive reactions

1. reaction to weak influences -
training reaction (according to Harkavy,
Kvakina, Ukolova)
2. response to medium impact
forces - activation reaction (according to
Garkavi, Kvakina, Ukolova)
3. reaction to strong, emergency
impact - stress reaction (according to G.
Selye)

57.

First impression of stress
(from English stress - stress)
formulated
Canadian
scientist Hans Selye in 1936 (1907-1982).
at first
for
designations
stress was used
general adaptation syndrome
(OSA).
Term
"stress"
become
use later.
Stress
special state of the body
humans and mammals, emerging
in response to a strong external stimulus stressor
-

58.

Stressor (synonyms: stress factor, stress situation) - a factor that causes a state
stress.
1. Physiological (excessive pain, loud noise,
exposure to extreme temperatures)
2. Chemical (taking a number of drugs,
e.g. caffeine or amphetamines)
3. Psychological
(information
overload,
competition,
a threat
social
status,
self-esteem, immediate environment, etc.)
4. Biological (infections)

59.

The classic triad of OAS:
1. bark growth
adrenal glands;
2. thymus reduction
glands (thymus);
3. ulceration of the stomach.

60. Mechanisms that increase the adaptive capacity of the body to a stressor in OSA:

Mobilization of energy resources (Increase
levels of glucose, fatty acids, amino acids and
ketone bodies)
Increasing the efficiency of external
breathing.
Strengthening and centralization of blood supply.
Increased blood clotting ability
Activation of the central nervous system (improvement of attention, memory,
reduction of reaction time, etc.).
Decreased feelings of pain.
Suppression of inflammatory reactions.
Decreased eating behavior and sexual desire.

61. Negative manifestations of OSA:

Immune suppression (cortisol).
Reproductive dysfunction.
Indigestion (cortisol).
Activation of LPO (adrenaline).
Tissue degradation (cortisol, adrenaline).
ketoacidosis, hyperlipidemia,
hypercholesterolemia.

62. Stages of change in the adaptive capacity of the body under stress

Level
resistance
1 - alarm phase
A - shock
B - antishock
2 - phase of resistance
3 - exhaustion phase
or adaptation
stressor
2
1
BUT
B
3
Diseases of adaptation, death
Time

63.

Stress, depending on the level change
adaptability is divided into:
eustress
(adaptation)
distress
(exhaustion)
the stress that
the stress that
adaptive
adaptive
body's capabilities
body's capabilities
rising, happening
are declining. Distress
its adaptation to
leads to the development
stress factor and
adaptation diseases,
elimination of stress.
possibly to death.

64. General adaptation syndrome

Develops with the participation of systems:
hypothalamic-pituitary-adrenal.
sympathetic-adrenal
hypothalamic-pituitary-thyroid axis
and hormones:
ACTH
corticosteroids (glucocorticoids,
mineralocorticoids, androgens, estrogens)
Catecholamines (adrenaline, norepinephrine)
TSH and thyroid hormones
STG

65. Regulation of hormone secretion during stress

Stress
CNS
SNS: paraganglia
Hypothalamus
Vasopressin
Pituitary
Brain
substance
adrenal glands
Adrenalin
Norepinephrine
ACTH
TSH
Cortical
substance
adrenal glands
Thyroid
gland
Thyroid
hormones
Glucocorticoids
Mineralocorticoids
Target tissues
STG
Liver
Somatomedins

66.

Level
persistence
Involvement of hormones in the stages of OSA
II stage - resistance
Hormones: cortisol, growth hormone.
eustress
III
I
II
time
distress
Stage I - anxiety
shock
countershock
Hormones:
adrenalin,
vasopressin,
oxytocin,
corticoliberin,
cortisol.
Stage III - adaptation or
exhaustion
When adapting:
- anabolic hormones:
(CTH, insulin, sex hormones).
When exhausted:
-decrease in adaptation hormones.
Damage accumulation.

67. Sympathetic-adrenal axis

Sympathoadrenal axis

68.

Synthesis of adrenaline
Oh
norepinephrine
Oh
O2
Oh
Fe2+
CH 2
HC
COOH
Tyr
Oh
Oh
HC
2+
Cu
CH 2
NH2
COOH
O2
Oh
Oh
H2C
NH2
dopamine
Oh
Oh
vit. FROM
B6
CH 2
NH2
CO2
SAM SAG
HC
IS HE
HC
H2C
NH2
H2C
norepinephrine
DOPA
DOPATHyrosindopamine monooxygenase decarboxylase monooxygenase
IS HE
NHCH 3
adrenalin
methyltransferase

69.

effects
Norepinephrine
Adrenalin
++++
+++
++++
++
++
++
Heat production
Reduction of MMC
+++
+++
++++
+ or -
Lipolysis (Mobilization of fatty
acids)
Synthesis of ketone bodies
Glycogenolysis
+++
++
+
+
+
+++
-
---
Arterial pressure
Heart rate
Peripheral resistance
Glycogenesis
Motility of the stomach and intestines
Sweat glands (sweat)
-
+
-
+

70. Hypothalamic-pituitary-adrenal axis

Hypothalamic-pituitary-adrenal axis
Hormones of the adrenal cortex
Corticosteroids
Glucocorticoids (cortisol) + stress, trauma,
hypoglycemia
Mineralocorticoids (aldosterone) +
hyperkalemia, hyponatremia, angiotensin II,
prostaglandins, ACTH
Androgens
Estrogens

71.

Synthesis scheme
corticosteroids

72.

corticotropin releasing hormone
corticotropic cells
anterior pituitary gland
dopamine
melanotropic cells
middle pituitary gland
Proopiomelanocortin (POMC)
241AK

73.

ACTH
Maximum secretion of ACTH (as well as liberin and
glucocorticoids) is observed in the morning at 6-8 o'clock, and
minimum - between 18 and 23 hours
ACTH
MC2R (receptor)
adrenal cortex
adipose tissue
glucocorticoids
lipolysis
melanocortinous
skin cell receptors
melanocytes, cells
immune system, etc.
Raise
pigmentation

74. Reactions of the synthesis of corticosteroids

mitochondrion
lipid
a drop
H2O
oily
acid
Ether
2
cholesterol
cholesterolesterase HO
ACTH
11
12
1 19
10
5
3
4
17
13
9
14
8
7
6
Cholesterol
24
22
18 21
20
23
25
CH 3
C O
26
27
16
15
cholesterol desmolase
P450
HO
Pregnenolone

75. Synthesis of cortisol and aldosterone

CH 3
C O
CH 3
C O
hydroxysteroid-dg
HO
cytoplasm
Pregnenolone
CH 3
C O
IS HE
O
Progesterone
EPR
17-hydroxylase
O
O
Hydroxyprogesterone
CH3OH
C O
EPR
21-hydroxylase
Desoxycorticosterone
11-hydroxylase
EPR 21-hydroxylase (P450)
CH3OH
C O
IS HE
O
O
Deoxycortisol
11-hydroxylase (P450)
mitochondrion
4HO
O
HO
CH3OH
C O
CH3OH3
C O
OH 2
Beam
and mesh
zone
1
Corticosterone
18-hydroxylase
mitochondrion
cortisol
HO
CH3OH
CHO C O
glomerular
zone
O
Aldosterone

76. Action of glucocorticoids (cortisol)

in the liver mainly have anabolic
effect (stimulates the synthesis of proteins and nucleic
acids).
in muscles, lymphoid and adipose tissue, skin and
bones inhibit the synthesis of proteins, RNA and DNA and
stimulates the breakdown of RNA, proteins, amino acids.
stimulate gluconeogenesis in the liver.
stimulate the synthesis of glycogen in the liver.
inhibit glucose uptake by insulin-dependent
tissues. Glucose goes to insulin-independent tissues
- CNS.

77. Action of mineralocorticoids (the main representative is aldosterone)

Stimulate:
Inhibit:
reabsorption of Na+ into
kidneys;
secretion of K+, NH4+, H+
in the kidneys, sweat,
salivary glands,
slime. shell
intestines.
synthesis of Na transporter proteins;
Na+,K+-ATPases;
synthesis of transporter proteins K+;
synthesis
mitochondrial
enzymes of the TCA.

78. Sex hormones

79. Synthesis of androgens and their precursors in the adrenal cortex

IN ADRENAL
CH 3
C O
Synthesis of androgens and their
predecessors in
adrenal cortex
CH 3
C O
EPR
HO
Pregnenolone
isomerase
O
EPR
hydroxylase
Progesterone
CH 3
C O
IS HE
HO
CH 3
C O
IS HE
O
Hydroxypregnenolone
Hydroxyprogesterone
ABOUT
ABOUT
HO
Dehydroepiandrosterone
mitochondrion
active
predecessor
hydroxylase
Androstenedione
inactive
predecessor
few
IS HE
HO
O
Androstenediol
few
IS HE
O
Testosterone
IS HE
few
HO
Estradiol

80. Regulation of synthesis and secretion of male sex hormones

-
Hypothalamus
Gonadotropin-releasing hormone
+
-
inhibin
-
Anterior Pituitary
FSH
+
Cells
Sertoli
LG
+
Cells
Leydig
testosterone
+
spermatogenesis

81. Regulation of synthesis and secretion of female sex hormones

+
-
Hypothalamus
Gonadotropin-releasing hormone
+
-
-
Anterior Pituitary
FSH
LG
+
+
Follicle
corpus luteum
estradiol
progesterone

82. Action of sex hormones

Androgens:
-regulate protein synthesis in the embryo
spermatogonia, muscles, bones,
kidneys and brain;
- have anabolic effect;
-stimulate cell division, etc..

83.

Estrogens:
- stimulate the development of tissues involved in
reproduction;
-determine the development of female secondary genitalia
signs;
- prepare the endometrium for implantation;
- anabolic effect on bones and cartilage;
-stimulate the synthesis of transport proteins
thyroid and sex hormones;
- increase HDL synthesis and inhibit
the formation of LDL, which leads to a decrease in cholesterol in
blood, etc.
- affects reproductive function;
-acts on the central nervous system, etc.

84.

Progesterone:
1. affects reproductive function
organism;
2. increases basal body temperature
after
3. ovulation and persists during luteal
phases of the menstrual cycle;
4. in high concentrations interacts with
renal aldosterone receptors
tubules (aldosterone loses its ability to
stimulate sodium reabsorption)
5. acts on the central nervous system, causing some
behavioral features in premenstrual
period.

85. Somatotropic hormone

STG
–
somatotropic
hormone
(hormone
growth),
single stranded
polypeptide of 191 AAs, has 2
disulfide bridges. Synthesized in
front
shares
pituitary gland
how
classical
proteinaceous
hormone.
Secretion is pulsed at intervals of
20-30 min.

86.

- somatoliberin
+ somatostatin
Hypothalamus
somatoliberin
somatostatin
-
+
-
Anterior Pituitary
STG
Liver
Bones
+ gluconeogenesis
+ protein synthesis
+ growth
+ protein synthesis
IGF-1
Adipocytes
muscles
+ lipolysis
- disposal
glucose
+ protein synthesis
- disposal
glucose

87.

Under the action of STH, tissues produce
peptides - somatomedins.
Somatomedins
or insulin-like
factors
growth
(FMI)
possess
insulin-like activity and potent
growth-promoting
action.
Somatomedins
possess
endocrine,
paracrine and autocrine action. They are
govern
activity
And
number
enzymes, protein biosynthesis.

Lecture No. 13 REGULATION OF METABOLISM. BIOCHEMISTRY OF HORMONES. 1 MECHANISM OF ACTION OF HORMONES THROUGH c. AMP and c. HMF

Purpose: To acquaint with the general properties of hormones, the first mechanisms of action of hormones, mediators of the transfer of hormone action within the cell

Plan: 1. General properties of hormones 2. The first mechanism through c. AMP 3. The first mechanism through c. HMF

Hormones are biologically active substances that are formed in glandular cells, released into the blood or lymph and regulate metabolism.

The leading link in the adaptation of the body is the central nervous system and the hypothalamic - pituitary system. The CNS, in response to irritation, sends nerve impulses to the hypothalamus and other tissues, including the endocrine glands, in the form of a change in the concentration of ions and mediators.

The hypothalamus secretes special substances - neurosecretins or releasing factors of two types: 1 Liberins, which accelerate the release of tropic pituitary glands 2: Statins, which inhibit their release.

Hypotalamus oxytocin, vasopressin adenogipophysine STG, TTG, ACTG, FSH, LTG, prolactin Epiphiz Melatonin Publishing Naya Iron Paranthomon Heart: Sodium Uretic Factor Thyroid Iron T 3, Tyroxin, Calcitonine Timus Timosin Adrenches Catecholamidera, Corticosteroidtar, Rhenin Minders Kidney Erythropoietin, Renin, Prostaglandin DIGESTINAL TRACT Gastrin, secretin PANCREAS insulin, glucagon GENERAL GLANDS Estradiol, progesterone, testosterone, relaxin, inhibin, human chorionic gonadotropin Endocrine system

Classification of hormones I. Protein-peptide hormones 1) Hormones - simple proteins (insulin, growth hormone, LTG, parathyroid hormone) 2) Hormones - complex proteins (TSH, FSH, LH) 3) Hormones - polypeptides (glucagon, ACTH, MSH, calcitonin , vasopressin, oxytocin) Some of these hormones are formed from inactive precursors - prohormones (for example, insulin and glucagon).

II. Steroid hormones are derivatives of cholesterol (corticosteroids, sex hormones: male, female). III. Hormones - derivatives of amino acids (thyroxine, triiodothyronine, adrenaline, norepinephrine).

General properties of hormones - strict specificity of biological action; - high biological activity; secretion; - distance action; - hormones can be in the blood, both in a free state and in a state connected with certain proteins; - short duration of action; All hormones act through receptors.

Hormone receptors (RCs) By their chemical nature, receptors are proteins, true glycoproteins. Tissues in which there are receptors for a given hormone are called target tissues (target cells).

The biological effect of the hormone depends not only on its content in the blood, but also on the number and functional state of receptors, as well as on the level of functioning of the post-receptor mechanism.

All known hormones are divided into 3 groups according to the mechanism of action: I) Membrane-cytosolic mechanism hormones that act by changing the activity of intracellular enzymes. These hormones bind to receptors on the outer surface of the target cell membrane, do not enter the cell and act through second messengers (messengers): c-AMP, c-GMP, calcium ions, inositol triphosphate.

2. Hormones that act by changing the rate of protein and enzyme synthesis. (Cytosolic.) These hormones bind to intracellular receptors: cytosolic, nuclear, or organoid receptors. These hormones include steroid and thyroid hormones.

3. Hormones that act by changing the permeability of the plasma membrane (membrane.) These hormones include insulin, growth hormone, LTH, ADH.

1st MECHANISM The adenylate cyclase system consists of 3 parts: I - the recognition part, represented by a receptor located on the outer surface of the cell membrane, . Part II - conjugating protein (G-protein). In its inactive form, the G protein is bound by its subunit to GDP.

Part III - catalytic is the enzyme adenylate cyclase adenylate cyclase ATP H 4 P 2 O 7 + c. AMP interacts with protein kinase A, which consists of 4 subunits: 2 regulatory, 2 catalytic.

Protein kinase A catalyzes the transfer of the phosphate group from ATP to the OH groups of serine and threonine of a number of proteins and enzymes of target cells, i.e. it is a serine-threonine kinase of ATP ADP Protein protein-P

Proteins to which phosphoric acid residues will be transferred during phosphorylation with the participation of protein kinase A can be some enzymes (for example, phosphorylase, lipase, glycogen synthetase, methyltransferases), proteins of ribosomes, nuclei, and membranes. During phosphorylation of inactive forms of phosphorylase and lipase, conformational changes are observed in their molecules, which leads to an increase in their activity.

Phosphorylation of glycogen synthetase, on the contrary, inhibits its activity. Attachment of phosphoric acid to ribosome proteins increases protein synthesis.

If phosphoric acid attaches to nuclear proteins, then the connection between the protein (histone) and DNA is weakened, which leads to increased transcription, and hence to increased protein synthesis. Phosphorylation of membrane proteins increases their permeability for a number of substances, in particular for ions.

Under the influence of hormones acting through c. AMP, accelerated: 1. Glycogenolysis by phosphorolysis, 2. lipolysis, 3. protein synthesis, 4. transport of ions across membranes, 5. inhibition of glycogenesis

Hormones act according to this mechanism through the guanylate cyclase system. Guanylate cyclase has membrane-bound and soluble (cytosolic) forms. The membrane-bound form consists of 3 sections: 1 - recognizing (on the outside of the plasma membrane)

2nd - Transmembrane 3rd - Catalytic The membrane-bound form of the enzyme is activated through receptors by short peptides, for example, atrial sodium uretic factor.

Natriuretic factor is synthesized in the atrium in response to an increase in circulating blood volume, enters the kidneys, activates guanylate cyclase in them, which leads to an increase in the excretion of sodium and water.

Smooth muscle cells also contain a guanylate cyclase system through which they are relaxed. Vasodilators act through this system, both endogenous (nitric oxide) and exogenous.

In intestinal epithelial cells, the activator of guanylate cyclase can be bacterial endotoxin, which leads to a slowdown in water absorption and diarrhea. Cytosolic form of guanylate cyclase heme-containing enzyme

Nitrovasodilators, reactive oxygen species (nitric oxide), lipid peroxidation products are involved in the regulation of its activity. Under the action of guanylate cyclase, c. GMP C-GMP acts on two-subunit protein kinase G

c. GMP binds to the regulatory sites of PK G, activating it. PKA and PK G are serine-threonine kinases, and by accelerating the phosphorylation of serine and threonine of various proteins and enzymes, they have different biological effects.

1) diuresis increases under the influence of the natriuretic factor (this hormone-peptide is formed in the atria) 2) diarrhea develops under the action of bacterial endotoxins

The same hormone can act through c. GMF and through c. AMF. The effect depends on which receptor the hormone binds to. For example, adrenaline can bind to both alpha and beta receptors.

The formation of a complex of adrenaline with beta receptors leads to the formation of c. AMF. The formation of a complex of adrenaline with alpha receptors leads to the formation of c. HMF. The effects of adrenaline will vary.

PC G increases the activity of glycogensitetase, inhibits platelet aggregation, activates phospholipase C, releasing Ca from its depot. That. , by its action c. GMF is an antagonist of c. AMF

3) under the action of nitric oxide, smooth muscle cells of blood vessels relax (which is used in medicine, since a number of nitro drugs, such as nitroglycerin, are used to relieve vasospasm)

Removal of a hormone signal acting through c. AMP and c. HMF occurs as follows: 1. the hormone is rapidly destroyed, and, consequently, the hormone-receptor complex is destroyed

2. to remove the hormonal signal in cells, there is a special enzyme phosphodiesterase, which converts cyclic nucleotides into nucleoside monophosphates (adenylic and guanylic acids, respectively)

T. Sh. Sharmanov, S. M. Pleshkova "Metabolic foundations of nutrition with a course of general biochemistry", Almaty, 1998 S. Tapbergenov "Medical biochemistry", Astana, 2001 S. Seitov "Biochemistry", Almaty, 2001 pp 342 -352, 369 - 562 V. J. Marshall "Clinical biochemistry", 2000 N. R. Ablaev Biochemistry in diagrams and drawings, Almaty 2005 pp 199 -212 Biochemistry. A short course with exercises and tasks. Ed. prof. E. S. Severina, A. Ya. Nikolaeva, M., 2002 Severin E. S. "Biochemistry" 2008, Moscow, pp 534 -603 Berezov T. T., Korovkin B. F. 2002 "Biological chemistry" , pp. 248-298.

Control questions: 1. General properties of hormones 2. Classification of hormones 3. Mediators of action of hormones of the first mechanism 4. The role of cAMP and cGMP

Lecture No. 14 Regulation of metabolism The first mechanism of action of hormones through calcium ions, DAG and ITP. Second and third mechanisms of action.

To acquaint with the features of the action of hormones through intermediaries: calcium ions, DAG, ITP, the action of steroid hormones - the second mechanism, the membrane mechanism Purpose:

The mediators of the action of hormones are calcium ions, DAG, ITP. The second mechanism of action Features of the action of hormones according to the third mechanism. Plan:

Inside the cell, the concentration of calcium ions is negligible (10¯7 mol/l), while outside the cell and inside the organelles it is higher (10¯3 mol/l).

The entry of calcium from the external environment into the cell is carried out through the calcium channels of the membrane. Calcium flux is regulated by Ca-dependent membrane ATPase; inositol triphosphate (IP 3) and insulin can play a regulatory role in the implementation of its function.

Inside the cell, Ca 2+ ions are deposited in the mitochondrial matrix and endoplasmic reticulum. Ca 2+ entering the cytoplasm from the external environment or from intracellular depots interacts with Ca 2+-dependent calmodulin kinase.

Calcium binds to the regulatory part of the enzyme, it is a calcium-binding protein - calmodulin, and the enzyme is activated.

Calmodulin has several centers (up to 4) for binding to calcium or magnesium ions. At rest, calmodulin is associated with magnesium, with an increase in the concentration of calcium in the cell, calcium displaces magnesium.

With a significant increase in calcium, a complex 4 Ca 2 + calmodulin is formed, which activates guanylate cyclase and phosphodiesterase c. AMF.

The action of hormones through calcium ions is often combined with the use of phosphatidylinositol derivatives as an intermediary. The receptor in such cases is in complex with the G protein and when the receptor interacts with the hormone (for example, TSH, prolactin, growth hormone)

there is an activation of the membrane-bound enzyme phospholipase C, which accelerates the decomposition reaction of phosphatidylinositol 4, 5-diphosphate with the formation of DAG and inositol-1, 4, 5-triphosphate.

DAG and inositol triphosphate are second messengers in the action of the respective hormones. DAG causes the activation of protein kinase C, which, in turn, causes phosphorylation of nuclear proteins, thereby increasing the proliferation of target cells.

Hormones that act by changing the permeability of the plasma membrane (membrane.) For various substrates (amino acids, glucose, glycerol, etc.)

These hormones bind to plasma membrane receptors and mediate their action through the tyrosine kinase-phosphatase system.

In this case, there is a change in the activity of intracellular enzymes, accompanied by the activation of transporter proteins and ion channels. These hormones include insulin, growth hormone, LTH, and ADH.

Hormones STH, LDH, forming a hormone receptor complex, activate cytosolic tyrosine kinase, which acts like a membrane-bound one, phospholipase C is activated, which leads to the mobilization of Ca +2 and activation of protein kinase C.

ADH acting through c. AMP causes the movement of water channels (protein-quaporins), increases water reabsorption in the kidneys, decreases urine output, i.e. ADH increases the permeability of target cell membranes for water.

T. Sh. Sharmanov, S. M. Pleshkova "Metabolic foundations of nutrition with a course of general biochemistry", Almaty, 1998 S. Tapbergenov "Medical biochemistry", Astana, 2001 S. Seitov "Biochemistry", Almaty, 2001 pp 342 -352, 369 - 562 V. J. Marshall "Clinical biochemistry", 2000 N. R. Ablaev Biochemistry in diagrams and drawings, Almaty 2005 pp 199 -212 Biochemistry. A short course with exercises and tasks. Ed. prof. E. S. Severina, A. Ya. Nikolaeva, M., 2002 Severin E. S. "Biochemistry" 2008, Moscow, pp. 534 -603 Berezov T. T., Korovkin B. F. "Biological Chemistry", pp. 248298. References:

Control questions: 1. The role of c. GMF in the mechanism of action of hormones 2. The role of Ca and ITP in the mechanism of action of hormones 3. The second mechanism is a change in the rate of protein-enzyme synthesis 4. The third mechanism is a change in the mechanism of cell membrane permeability.