Receiving hormones. Obtaining and using hormones. Dopamine: my favorite

Everyone more or less understands what hormones are. Until recently, it was generally accepted that they were synthesized by endocrine glands or specialized endocrine cells scattered throughout the body and united in a diffuse endocrine system. Cells of the diffuse endocrine system develop from the same germ layer as the nervous ones, and therefore are called neuroendocrine. Where they were found: in the thyroid gland, adrenal medulla, hypothalamus, pineal gland, placenta, pancreas and gastrointestinal tract. And recently they were discovered in the dental pulp, and it turned out that the number of neuroendocrine cells in it varies depending on the health of the teeth.

The honor of this discovery belongs to Alexander Vladimirovich Moskovsky, Associate Professor of the Department of Orthopedic Dentistry of the Medical Institute at the Chuvash State University named after. I. N. Ulyanova. Neuroendocrine cells are distinguished by characteristic proteins and can be identified by immunological methods. This is exactly how A.V. Moskovsky discovered them. (This study was published in No. 9 of the Bulletin of Experimental Biology and Medicine, 2007.)

Pulp is the soft core of the tooth that contains nerves and blood vessels. It was removed from the teeth and sections were prepared, on which specific proteins of neuroendocrine cells were then looked for. They did this in three stages. First, the prepared sections were treated with antibodies to the desired proteins (antigens). Antibodies consist of two parts: specific and nonspecific. After binding to antigens, they remain on the section with the nonspecific part facing up. The section is treated with antibodies to this nonspecific part, which are labeled with biotin. Then this “sandwich” with biotin on top is treated with special reagents, and the location of the original protein appears as a reddish spot.

Neuroendocrine cells differ from connective tissue cells in their larger size, irregular shape, and the presence of reddish-brown lumps (colored proteins) in the cytoplasm, often covering the nucleus.

There are few neuroendocrine cells in a healthy pulp, but with caries their number increases. If the tooth is not treated, the disease progresses, and the number of neuroendocrine cells increases, and they accumulate around the lesion. The peak of their numbers occurs when caries is so advanced that the tissues around the tooth become inflamed, that is, periodontitis begins.

Patients who prefer to suffer at home for a long time rather than go to the doctor once develop inflammation of the pulp and periodontium. At this stage, the number of neuroendocrine cells decreases (although there are still more of them than in a healthy pulp) - they are replaced by inflammatory cells (leukocytes and macrophages). Their number also decreases in chronic pulpitis, but with this disease there are generally few cells left in the pulp; they are replaced by sclerotic cords.

According to A.V. Moskovsky, neuroendocrine cells in caries and pulpitis regulate the processes of microcirculation and metabolism at the site of inflammation. Since there are also more nerve fibers during caries and pulpitis, the endocrine and nervous systems act together in this matter.

Are hormones everywhere?

In recent years, scientists have discovered that the production of hormones is by no means the prerogative of specialized endocrine cells and glands. This is also done by other cells that have many other tasks. Their list grows year by year. It contains various blood cells (lymphocytes, eosinophilic leukocytes, monocytes and platelets), macrophages crawling outside the blood vessels, endothelial cells (the lining of blood vessels), thymic epithelial cells, chondrocytes (from cartilage tissue), cells of the amniotic fluid and placental trophoblast (that parts of the placenta, which grows into the uterus) and endometrium (this is from the uterus itself), Leydig cells of the testes, some retinal cells and Merkel cells located in the skin around the hair and in the epithelium of the subungual bed, muscle cells. The list of hormones they synthesize is also quite long.

Take, for example, mammalian lymphocytes. In addition to their required antibody production, they synthesize melatonin, prolactin, ACTH (adrenocorticotropic hormone) and somatotropic hormone. The “homeland” of melatonin is traditionally considered to be the pineal gland, a gland located deep in the human brain. It is also synthesized by cells of the diffuse neuroendocrine system. The spectrum of action of melatonin is wide: it regulates biorhythms (for which it is especially famous), differentiation and cell division, suppresses the growth of certain tumors and stimulates the production of interferon. Prolactin, which causes lactation, is produced by the anterior pituitary gland, but in lymphocytes it acts as a cell growth factor. ACTH, which is also synthesized in the anterior pituitary gland, stimulates the synthesis of steroid hormones of the adrenal cortex, and in lymphocytes regulates the formation of antibodies.

And the cells of the thymus, the organ in which T-lymphocytes are formed, synthesize luteinizing hormone (a pituitary hormone that causes the synthesis of testosterone in the testes and estrogens in the ovaries). In the thymus, it probably stimulates cell division.

Many experts consider the synthesis of hormones in lymphocytes and thymus cells as evidence of the existence of a connection between the endocrine and immune systems. But this is also a very indicative illustration of the current state of endocrinology: it cannot be said that a certain hormone is synthesized there and does this. There can be many places of its synthesis, as well as functions, and often they depend precisely on the place of formation of the hormone.

Endocrine layer

Sometimes an accumulation of nonspecific hormone-producing cells forms a full-fledged endocrine organ, and a rather large one, such as adipose tissue. However, its size is variable, and depending on it, the spectrum of “fat” hormones and their activity change.

Fat, which causes so much trouble for modern man, is in fact a most valuable evolutionary acquisition.

In the 1960s, American geneticist James Neal formulated the “thrifty genes” hypothesis. According to this hypothesis, the early history of mankind, and not only the early history, was characterized by periods of prolonged starvation. Those who survived were those who, in the intervals between hungry years, managed to eat up so that later they would have something to lose weight. Therefore, evolution selected alleles that contributed to rapid weight gain, and also inclined a person to low mobility - sitting still, fat cannot be shaken off. (Several hundred genes that influence behavioral style and the development of obesity are already known.) But life has changed, and these internal reserves are now not useful to us, but to illness. Excess fat causes a serious illness - metabolic syndrome: a combination of obesity, insulin resistance, high blood pressure and chronic inflammation. A patient with metabolic syndrome does not have long to wait for cardiovascular diseases, type 2 diabetes and many other ailments. And all this is the result of the action of adipose tissue as an endocrine organ.

The main cells of adipose tissue, adipocytes, are not at all like secretory cells. However, they not only store fat, but also secrete hormones. The main one, adiponectin, prevents the development of atherosclerosis and general inflammatory processes. It affects the signal transmission from the insulin receptor and thereby prevents the occurrence of insulin resistance. Under its influence, fatty acids in muscle and liver cells are oxidized faster, reactive oxygen species become fewer, and diabetes, if it already exists, is easier. Moreover, adiponectin regulates the functioning of adipocytes themselves.

It would seem that adiponectin is indispensable for obesity and can prevent the development of metabolic syndrome. But, alas, the more adipose tissue grows, the less hormone it produces. Adiponectin is present in the blood in the form of trimers and hexamers. With obesity, there are more trimers and fewer hexamers, although hexamers interact much better with cellular receptors. And the number of receptors itself decreases with the growth of adipose tissue. So the hormone not only becomes smaller, it also acts weaker, which, in turn, contributes to the development of obesity. It turns out to be a vicious circle. But you can break it - lose 12 kilograms, no less, then the number of receptors returns to normal.

Another wonderful hormone in adipose tissue is leptin. Like adipokinetin, it is synthesized by adipocytes. Leptin is known to suppress appetite and speed up the breakdown of fatty acids. It achieves this effect by interacting with certain neurons of the hypothalamus, and then the hypothalamus itself decides. With excess body weight, the production of leptin increases significantly, and the neurons of the hypothalamus reduce sensitivity to it, and the hormone wanders through the blood unbound. Therefore, although leptin levels in the serum of obese patients are elevated, people do not lose weight because the hypothalamus does not perceive its signals. However, there are leptin receptors in other tissues, their sensitivity to the hormone remains at the same level, and they readily respond to its signals. And leptin, by the way, activates the sympathetic part of the peripheral nervous system and increases blood pressure, stimulates inflammation and promotes the formation of blood clots, in other words, it makes a strong contribution to the development of hypertension and inflammation characteristic of metabolic syndrome.

The development of inflammation and insulin resistance is also caused by another adipocyte hormone, resistin. Resistin is an insulin antagonist; under its action, cardiac muscle cells reduce glucose consumption and accumulate intracellular fats. And adipocytes themselves, under the influence of resistin, synthesize much more inflammatory factors: chemotactic protein 1 for macrophages, interleukin-6 and tumor necrosis factor-b (MCP-1, IL-6 and TNF-b). The more resistin in the serum, the higher the systolic pressure, the wider the waist, the greater the risk of developing cardiovascular diseases.

In fairness, it should be noted that the expanding adipose tissue seeks to correct the damage caused by its hormones. For this purpose, adipocytes of obese patients produce two more hormones in excess: visfatin and apelin. True, their synthesis also occurs in other organs, including skeletal muscles and the liver. In principle, these hormones resist the development of metabolic syndrome. Visfatin acts like insulin (binds to the insulin receptor) and reduces blood glucose levels, and also activates adiponectin synthesis in a very complex way. But this hormone cannot be called unconditionally useful, since visfatin stimulates the synthesis of inflammatory signals. Apelin suppresses insulin secretion by binding to pancreatic beta cell receptors, lowers blood pressure, and stimulates contraction of heart muscle cells. As the mass of adipose tissue decreases, its content in the blood decreases. Unfortunately, apelin and visfatin cannot counteract the action of other adipocyte hormones.

The hormonal activity of adipose tissue explains why excess weight leads to such serious consequences. However, scientists have recently discovered a larger endocrine organ in the body of mammals. It turns out that our skeleton produces at least two hormones. One regulates bone mineralization processes, the other regulates cell sensitivity to insulin.

The bone takes care of itself

Readers of Chemistry and Life know, of course, that bone is alive. It is built by osteoblasts. These cells synthesize and secrete large amounts of proteins, mainly collagen, osteocalcin and osteopontin, which create the organic matrix of bone, which is then mineralized. During mineralization, calcium ions bind to inorganic phosphates to form hydroxyapatite. Having surrounded themselves with a mineralized organic matrix, osteoblasts turn into osteocytes - mature, multi-processed spindle-shaped cells with a large round nucleus and a small number of organelles. Osteocytes do not come into contact with the calcified matrix; between them and the walls of their “caves” there is a gap of about 0.1 µm wide, and the walls themselves are lined with a thin, 1–2 µm, layer of non-mineralized tissue. Osteocytes are connected to each other by long processes passing through special tubules. Through these same tubules and cavities around osteocytes, tissue fluid circulates, nourishing the cells.

Bone mineralization occurs normally if several conditions are met. First of all, a certain concentration of calcium and phosphorus in the blood is necessary. These elements enter food through the intestines and exit through urine. Therefore, the kidneys, filtering urine, must retain calcium and phosphorus ions in the body (this is called reabsorption).

Proper absorption of calcium and phosphorus in the intestine is ensured by the active form of vitamin D (calcitriol). It also affects the synthetic activity of osteoblasts. Vitamin D is converted to calcitriol by the enzyme 1b-hydroxylase, which is synthesized mainly in the kidneys. Another factor influencing the level of calcium and phosphorus in the blood and the activity of osteoblasts is parathyroid hormone (PTH), a product of the parathyroid glands. PTH interacts with bone, kidney and intestinal tissues and reduces reabsorption.

But recently, scientists have discovered another factor that regulates bone mineralization - the protein FGF23, fibroblast growth factor 23. (Major contributions to this work were made by employees of the pharmaceutical research laboratory of the Kirin Brewing Company and the Department of Nephrology and Endocrinology of the University of Tokyo under the direction of Takeyoshi Yamashita. Synthesis of FGF23 occurs in osteocytes, and it acts on the kidneys, controlling the level of inorganic phosphates and calcitriol.

As Japanese scientists have found, the gene FGF23(hereinafter genes, as opposed to their proteins, are indicated in italics) are responsible for two serious diseases: autosomal dominant hypophosphatemic rickets and osteomalacia. To put it simply, rickets is impaired mineralization of growing children's bones. And the word “hypophosphatemic” means that the disease is caused by a lack of phosphates in the body. Osteomalacia is the demineralization (softening) of bone in adults caused by a lack of vitamin D. Patients suffering from these diseases have elevated levels of the FGF23 protein. Sometimes osteomalacia occurs as a result of the development of a tumor, and not a bone one. FGF23 expression is also increased in the cells of such tumors.

All patients with overproduction of FGF23 have a decreased level of phosphorus in the blood, and renal reabsorption is weakened. If the described processes were under the control of PTH, then a violation of phosphorus metabolism would lead to increased formation of calcitriol. But this doesn't happen. In both types of osteomalacia, serum calcitriol concentrations remain low. Consequently, in the regulation of phosphorus metabolism in these diseases, the first violin is played not by PTH, but by FGF23. As scientists have found, this enzyme suppresses the synthesis of 1b-hydroxylase in the kidneys, which is why there is a lack of the active form of vitamin D.

With a lack of FGF23, the picture is the opposite: there is an excess of phosphorus in the blood, as well as calcitriol. A similar situation occurs in mutant mice with increased protein levels. And in rodents with the missing gene FGF23 the opposite is true: hyperphosphatization, increased renal phosphate reabsorption, high calcitriol levels and increased expression of 1β-hydroxylase. As a result, the researchers concluded that FGF23 regulates phosphate metabolism and vitamin D metabolism, and this regulatory pathway is different from the previously known pathway involving PTH.

Scientists are now understanding the mechanisms of action of FGF23. It is known to reduce the expression of proteins responsible for the uptake of phosphate in the renal tubules, as well as the expression of 1b-hydroxylase. Since FGF23 is synthesized in osteocytes and acts on kidney cells, getting there through the blood, this protein can be called a classical hormone, although no one would dare to call the bone an endocrine gland.

The level of the hormone depends on the content of phosphate ions in the blood, as well as on mutations in some genes that also affect mineral metabolism ( FGF23 after all, it is not the only gene with such a function), and from mutations in the gene itself. This protein, like any other, remains in the blood for a certain time and is then broken down by special enzymes. But if, as a result of mutation, the hormone becomes resistant to breakdown, there will be too much of it. And there is also a gene GALNT3, the product of which breaks down the FGF23 protein. A mutation in this gene causes increased breakdown of the hormone, and with a normal level of synthesis, the patient experiences a lack of FGF23 with all the ensuing consequences. There is a protein called KLOTHO, which is necessary for the interaction of the hormone with the receptor. And somehow FGF23 interacts with PTH, of course. Researchers suggest that it suppresses the synthesis of parathyroid hormone, although they are not entirely sure. But scientists continue to work and will soon, apparently, analyze all the actions and interactions of FGF23 to the last bone. Let's wait.

Skeleton and diabetes

Of course, proper bone mineralization is impossible without maintaining normal levels of calcium and phosphate in the blood serum. Therefore, it is understandable that the bone “personally” controls these processes. But what does she, one might ask, care about cell sensitivity to insulin? However, in 2007, researchers from Columbia University (New York) led by Gerard Karsenty discovered, to the great surprise of the scientific community, that osteocalcin affects the sensitivity of cells to insulin. This, as we remember, is one of the key proteins of the bone matrix, second in importance after collagen, and it is synthesized by osteoblasts. Immediately after synthesis, a special enzyme carboxylates three glutamic acid residues of osteocalcin, that is, it introduces carboxyl groups into them. It is in this form that osteocalcin is incorporated into bone. But some of the protein molecules remain uncarboxylated. This osteocalcin is designated uOCN, and it has hormonal activity. The process of carboxylation of osteocalcin enhances osteotesticular protein tyrosine phosphatase (OST-PTP), thereby reducing the activity of the hormone uOCN.

It started with American scientists creating a line of “non-osteocalcic” mice. The synthesis of bone matrix in such animals occurred at a higher rate than in normal animals, so the bones turned out to be more massive, but performed their functions well. In these same mice, the researchers found hyperglycemia, low insulin levels, few and decreased activity of insulin-producing pancreatic beta cells, and increased visceral fat. (Fat can be subcutaneous and visceral, deposited in the abdominal cavity. The amount of visceral fat depends mainly on nutrition, and not on genotype.) But in mice defective in the OST-PTP gene, that is, with excessive uOCN activity, the clinical picture is the opposite: too a lot of beta cells and insulin, increased sensitivity of cells to insulin, hypoglycemia, almost no fat. After injections of uOCN, the number of beta cells, the activity of insulin synthesis and sensitivity to it increase in normal mice. Glucose levels return to normal. So uOCN is a hormone that is synthesized in osteoblasts and acts on pancreatic cells and muscle cells. And it affects insulin production and sensitivity to it, respectively.

All this was established on mice, but what about people? According to a few clinical studies, osteocalcin levels are positively associated with insulin sensitivity, and in the blood of diabetics it is significantly lower than in people without the disease. However, in these studies, doctors did not distinguish between carboxylated and non-carboxylated osteocalcin. The role these forms of protein play in the human body remains to be understood.

But what is the role of the skeleton, it turns out! But we thought it was a support for muscles.

FGF23 and osteocalcin are classical hormones. They are synthesized in one organ and affect others. However, their example shows that the synthesis of hormones is not always a specific function of selected cells. It is rather general biological and is inherent in any living cell, regardless of its main role in the body.

Not only has the line between endocrine and non-endocrine cells been erased, the very concept of “hormone” is becoming increasingly vague. For example, adrenaline, dopamine and serotonin are certainly hormones, but they are also neurotransmitters, because they act both through the blood and through the synapse. And adiponectin has not only an endocrine effect, but also a paracrine one, that is, it acts not only through the blood on distant organs, but also through tissue fluid on neighboring adipose tissue cells. So the subject of endocrinology is changing before our eyes.

Hormones are widely used for diseases associated with disruption of the endocrine system: with a deficiency or absence in the body of a particular hormone (for example, insulin) or to enhance or suppress the function of a particular gland. Thus, the pituitary hormones adrenocorticotropin and thyrotropin can be used to stimulate the work of peripheral glands - the adrenal cortex itself and the thyroid gland. And since the hormones of the peripheral glands suppress the secretion of pituitary hormones, corticotropin, for example, will prevent the formation of adrenocorticotropic hormone.

Hormones are widely used in obstetrics and gynecology. Human chorionic gonadotropin helps in the treatment of infertility, oxytocin is used to enhance labor, prolactin stimulates milk secretion after childbirth. Steroid sex hormones or their analogues are used for disorders in the sexual sphere, as contraceptives, etc. Hormones of the adrenal cortex are used for inflammatory processes, allergic diseases, rheumatoid arthritis and a number of others. Hormones produced by the thymus gland (thymus) and stimulating the maturation of T-lymphocytes are used to treat cancer and immune disorders.

Getting hormones

Many non-peptide hormones and low molecular weight peptide hormones are produced by chemical synthesis. Polypeptide and protein hormones are isolated by extraction from the glands of livestock followed by purification. A procedure has been developed for obtaining certain hormones (including insulin and growth hormone) using genetic engineering methods. To do this, the gene responsible for the synthesis of a particular hormone is included in the genome of bacteria, which then acquire the ability to synthesize the desired hormone. Since bacteria actively multiply, it is possible to produce quite significant amounts of it in a short time.

PHYTOHORMONES (growth substances), chemical substances produced in plants and regulating their growth and development. They are formed mainly in actively growing tissues at the tops of roots and stems. Phytohormones usually include auxins, gibberellins and cytokinins, and sometimes growth inhibitors, for example. abscisic acid. Unlike animal hormones, they are less specific and often exert their effect in the same area of ​​the plant where they are formed. Many synthetic substances have the same effect as natural phytohormones.

PHYTOHORMONES(plant hormones), organic substances of small molecular weight, formed in small quantities in some parts of multicellular plants and acting on other parts as regulators and coordinators of growth and development. Hormones appear in complex multicellular organisms, including plants, as specialized regulatory molecules for the implementation of the most important physiological programs that require the coordinated work of various cells, tissues and organs, often significantly distant from each other. Phytohormones carry out biochemical regulation - the most important system for regulating ontogenesis in multicellular plants. Compared to animal hormones, the specificity of phytohormones is less pronounced, and the effective concentrations are usually higher. Unlike animals, plants do not have specialized organs (glands) that produce hormones.

There are 5 main groups of phytohormones, widespread not only among higher but also lower multicellular plants. These are auxins, cytokinins, gibberellins, abscisins and ethylene. Each group of phytohormones produces its own characteristic effect, which is similar in plants of different species. In addition to the five “classical” phytohormones, other endogenous substances are known for plants, in some cases acting similarly to phytohormones. These are brassinosteroids, (lipo)oligosaccharins, jasmonic acid, salicylic acid, peptides, polyamines, fusicoccin-like compounds, and phenolic growth inhibitors. Together with phytohormones, they are referred to by the general term “natural plant growth regulators.”

Currently, methods for the chemical synthesis of many non-peptide and low-molecular peptide hormones have been developed. Polypeptide and protein hormones are isolated by extraction from the endocrine glands of cattle. A method for producing certain hormones (including insulin and growth hormone), based on the principles of genetic engineering, has been developed. To do this, the gene responsible for the synthesis of a particular hormone is included in the genome of bacteria, which then acquire the ability to synthesize this hormone. Since bacteria actively multiply, in a short time it is possible to produce quite significant amounts of the desired hormone.

The use of hormones for therapeutic purposes is one of the areas of practical medicine. Hormones are widely used for diseases associated with endocrine system disorders: with a deficiency or absence of a particular hormone in the body (for example, insulin); to enhance or suppress the function of a particular gland. Thus, pituitary hormones can be used to stimulate the work of peripheral endocrine glands - the adrenal cortex and thyroid gland. Hormones are widely used in obstetrics and gynecology, for example, oxytocin is used to enhance labor. Steroid sex hormones or their analogues are used for disorders in the sexual sphere, as contraceptives, etc. In inflammatory processes, allergic diseases, rheumatoid arthritis and a number of other diseases, hormones of the adrenal cortex are used.

45. Biochemistry of the nervous system. Chemical mechanisms of memory.

All of the above phenomena, which have a specific physical and chemical nature and ultimately form the nervous system of the body, determine the ability of the brain to control behavior and carry out mental activity, i.e., the ability of a living being to perceive the reality around it and adapt to it in order to reproduce offspring, support the existence of the species, etc. As a result of this, we can conclude that the molecular phenomena underlying the mental activity of living beings constitute a fundamental and integral part of the evolutionary process.

Memory is not concentrated in one strictly localized area of ​​the brain, like the centers of vision or hearing. The substrate of memory is neurons. Cognition as a process is reflected in the chemistry of brain neurons and is manifested, for example, in changes in the uridine content in RNA, the degree of DNA methylation, phosphorylation of complex proteins of cell nuclei, the synthesis of new proteins, neurotransmitters, RNA and other biologically active molecules. It is customary to distinguish three forms of biological memory: genetic(its carrier is DNA), immunological(includes genetic, but has a higher level) and neurological. The last form of memory is the most complex; it conventionally divides short-term And long-term forms. Short-term memory is based on the circulation of information impulses along closed circuits of neurons. The inclusion of long-term memory proteins is ensured approximately 10 minutes after the arrival of information into the cell and consists of the targeted synthesis of RNA, specific proteins and the establishment of new synaptic connections; It is the biologically active molecules synthesized as a result of this process that are the repository of information in the body.

46. ​​Biochemistry of the nervous system. Chemistry of sensations. Sensation of taste.

All sensations are based on chemical phenomena that determine the activity of neurons in the central nervous system.

Sense of taste. The sense of taste can serve as an example chemoreception. The adult tongue contains about 9,000 taste buds, each consisting of 50 to 100 specialized messenger cells connected to neurons and responsible for the perception of the four basic taste sensations (sweet, salty, sour and bitter) caused by various substances.

The necessary conditions for a substance to exhibit any taste are: sufficiently good solubility in water and the presence of a certain spatial arrangement in the molecule of atoms with pronounced donor-acceptor properties.

Responsible for sweet taste fragments of molecules are called glucophores. It is assumed that the structure of the glucophore corresponds to the structure of the receptor protein of the mediator cell. When a “sweet” molecule interacts (mainly through hydrogen bonds) with the corresponding protein radicals, a change in its supramolecular structure occurs. The resulting signal is transmitted from the mediator cell to the neuron associated with it and then through the system of neurons to the brain. Currently, several models of the structural and functional organization of glucophores have been proposed.

These requirements are best met by the cyclic form of the fructose molecule, which tastes like the sweetest of sugars. Sucrose is 1.5 times sweeter than glucose, which is probably due to the presence in its molecule of two glucophores, the orientation of which is preferable for interaction with two receptors at once. Starch, although it contains many glucophores, does not give a sweet taste, since the large size of its polymer molecular chain does not allow individual glucose residues to approach the receptors and form the desired structure. The sweet taste is caused by molecules of polyhydric alcohols (ethylene glycol, glycerin, sorbitol) and a number of α-amino acids.

Sour taste caused by the presence of hydrogen ions formed during the dissociation of various acids (for example, acetic, carbonic or phosphoric), added to drinks such as cola to improve taste. It is assumed that taste buds located on the side of the tongue contain a large number of carboxyl groups (-COO~) ionized at the pH of the oral cavity. In an acidic environment, the acid-base equilibrium shifts towards the formation of the protonated form of the protein (-COOH). As a result, the total charge on the surface of the protein and its supramolecular structure change. Changing the shape of protein molecules initiates a corresponding signal that travels through neural circuits to the brain.

Bitter taste often caused by the presence of nitrogen-containing organic substances - alkaloids, which are usually poisonous, and the ability to detect them by taste was developed in humans, probably in the process of evolution. For a substance to exhibit a bitter taste, the following conditions are necessary: ​​solubility in water, the presence in the molecule of several amino or nitro groups oriented in a certain order. This is a striking example of how small changes in the structure of molecules can cause dramatic changes in their taste properties.

Adding bitter substances to aperitifs stimulates the secretion of saliva, which facilitates the digestion of incoming products (in primitive times, the secretion of saliva was the body’s protective reaction to poison, which usually has a bitter taste). An example of such substances is quinine, added to drinks such as tonic water.

Burning , spicy And cold taste are options for chemical pain modeling. Many spices stimulate the endings of pain neurons in the mouth, which, through a system of signals transmitted through thin (“quick” pain) and thick (“ slow» pain) nerve fibers that carry information to the brain. In response to such signals, brain cells synthesize neurotransmitters - analgesics peptide nature: endorphins and enkephalins.

Many alkaloids cause a burning taste - such as piperine (the active principle of white and black pepper), capsaicin (found in red and green pepper):

The pleasant sensation experienced after eating food flavored with fiery spices is attributed to the ability of these compounds to stimulate the formation of calming endorphins in brain cells.

The feeling of cold in the mouth caused by compounds such as menthol is due to the fact that the molecules of these substances are the “key” to the same protein receptors that, by changing their conformation, respond to a decrease in temperature. By interacting with menthol molecules, such receptors are activated at higher temperatures, initiating a signal in the corresponding brain neurons. As a result, in the presence of menthol, the central nervous system of the human body perceives warm objects in the oral cavity as cold.

Recent studies by Japanese scientists have shown the presence of a special receptor "umami" responsible for the taste of meat food. It consists of two protein molecules, one of which also reacts to bitter and sweet. The human umami receptor is most sensitive to glutamic acid, the sodium salt of which has long been used as a seasoning.

47. Biochemistry of the nervous system. Chemistry of sensations. Sense of smell.

Sense of smell. The sense of smell is also an example chemoreception. The human sense of smell is much more sensitive than the taste organs. Their work is ensured by 50 million protein receptors located on an area of ​​~5 cm 2 of the nasal epithelium. These receptors are exposed nerve endings. Olfaction is one of the most ancient and primitive senses, through which the central nervous system has direct contact with the outside world. In addition, the processes occurring during chemoreception are closely related to the limbic system, the center for controlling emotions. This explains the powerful, often subconscious influence of odors on the human condition.

Molecules with odor - osmophores must have a strictly defined structure, be volatile and soluble in an aqueous solution of proteins, carbohydrates and electrolytes covering the nerve endings in the nose. The osmophore interacts with a specific protein fragment,

changes its conformation and thus stimulates the transmission of a signal to the brain. Apparently, the key-lock mechanism works in this case as well. But the specificity and variety of options for its implementation are very great. It has been established that there are at least 30 different types of receptor proteins in the olfactory epithelium.

To initiate the corresponding signal, it is sufficient that the structure of the active center of the receptor corresponds to the spatial-chemical structure of even part of the osmophore molecule. If the osmophore molecule is flexible enough, it can interact with several receptor proteins and cause mixed odor sensations. While the active center of the receptor is occupied by an osmophore molecule, other molecules cannot form a corresponding complex with this receptor, and the nasal cavity ceases to smell.

The influence of the structure of osmophore molecules on their properties can be assessed using the following examples. Benzaldehyde, like hydrocyanic acid, causes a bitter almond odor. Phenylethanal, which differs slightly in molecular structure from benzaldehyde, causes the hyacinth odor.

A typical fruity odor is produced by many esters containing about seven carbon atoms and formed in fruits by the breakdown of long-chain fatty acids. Sulfur compounds like diallyl sulfide are responsible for the pungent odor of garlic and onions. As soon as you cut the plant, that is, mechanically destroy the cells, enzymes instantly come into contact with their contents and catalyze the metabolic processes of converting sulfur-containing amino acids into volatile molecules of these compounds.

The quintessence of the smell of plants are essential oils, obtained by steam distillation and extraction and containing substances whose molecules mainly contain about 10 carbon atoms and are often isoprene derivatives - terpenes. Such compounds have moderate volatility and a sufficient variety of structures; they are actually tiny aromatic fragments of rubber.

48. Biochemistry of the immune system. Chemical nature of antibodies.

Antibodies (immunoglobulins) - a special class of glycoproteins present on the surface of B lymphocytes in the form of membrane-bound receptors and in blood serum and tissue fluid in the form of soluble molecules, and have the ability to bind very selectively to specific types of molecules, which in this regard are called antigens. Antibodies are the most important factor in specific humoral immunity. Antibodies are used by the immune system to identify and neutralize foreign objects - such as bacteria and viruses. Antibodies perform two functions: antigen-binding and effector (they cause one or another immune response, for example, they trigger the classical scheme of complement activation).

Antibodies are synthesized by plasma cells, which become some B lymphocytes, in response to the presence of antigens. For each antigen, specialized plasma cells corresponding to it are formed, producing antibodies specific to this antigen. Antibodies recognize antigens by binding to a specific epitope - a characteristic fragment of the surface or linear amino acid chain of the antigen.

Antibodies are oligomeric proteins. To date, about ten groups of different antibodies are known, among which the most common groups in humans are IgG, IgA, IgM, IgD And IgE. The structural basis of immunoglobulins is made up of four polypeptide chains connected to each other by disulfide bridges. Two heavy chains (chains H) have a molecular weight of about 50,000 and contain from 450 to 700 amino acid residues each, and two light chains (chains L) include about 200 amino acid residues each and have a molecular weight of about 25,000. This structure is usually classified as monomers. Based on differences in the primary structure, light chains are divided into two types (χ and λ), and heavy chains into five types (α, γ, μ, δ, ε). It is depending on the type of heavy chain included in the monomer that all immunoglobulins are divided into several groups listed above. Each group includes a huge number of individual immunoglobulins, differing in primary structure.

1. Hormones are used to make up for their deficiency in the body with hypofunction of the endocrine glands (replacement therapy):

insulin – for diabetes;

thyroxine – for hypofunction of the thyroid gland;

somatotropin – for pituitary dwarfism;

deoxycorticosterone – for the treatment of hypocortisolism;

mineralocorticoids - for Addison's disease, hypocortisolism;

estrogen drugs – for pathological conditions associated with insufficient ovarian function, to restore disrupted sexual cycles;

androgen drugs – for hypofunction of the testes, functional disorders in the reproductive system.

Using the properties of hormones for the treatment of specific diseases:

glucocorticoids (cortisone, hydrocortisone) and their analogues (prednisolone, dexamethasone, etc.) are used to treat allergic and autoimmune diseases (rheumatoid arthritis, rheumatism, collagenosis, bronchial asthma, dermatitis), as anti-inflammatory and immunosuppressive agents (to suppress the rejection of transplanted organs) ; for the prevention and treatment of shock;

vasopressin – for diabetes insipidus;

oxytocin - to stimulate labor;

calcitonin – for osteoporosis, delayed healing of fractures, periodontal disease;

parathyroid hormone – for hypocalcemia caused by postoperative hypoparathyroidism;

glucagon – for hypoglycemia;

estrogen drugs and their combinations with progestins - for menopausal syndrome;

prostaglandins E - for hypertension, bronchial asthma, stomach ulcers, prostaglandins F - for termination of pregnancy, stimulation of labor;

drugs with prolactin activity (lactin) – for insufficient lactation in the postpartum period.

Usage synthetic hormone analogues:

glucocorticoid analogues (see 2);

analogues of female sex hormones – oral contraceptives;

synthetic estrogens (diethylstilbestrol and sinestrol) - for the treatment of prostate tumors;

a synthetic analogue of testosterone (testosterone propionate) – for the treatment of breast tumors;

anabolic steroids - methylandrostenediol, nerobolil, retabolil, etc. (see above).

Chapter 14 Nutritional Biochemistry

The science of food and nutrition is called nutritionology (from the Greek. nutritional- nutrition). Nutriciology or the science of nutrition - is the science of food, nutrients and other components contained in food products, their interactions, their role in maintaining health or the occurrence of diseases, and the processes of their consumption, assimilation, transfer, utilization (consumption) and elimination from the body.

Metabolic processes are the basis of life activity. Organic and inorganic substances enter the body from the external environment and undergo various chemical transformations. Nutrients are used to renew the components of cells of tissues and organs, for the growth of the body, as well as for energy purposes. All nutrients are divided into 6 main groups - carbohydrates, proteins, fats, vitamins, minerals and water.

With the oxidative breakdown of organic substances in food, chemical energy is released, which is used for life. The need for food is determined by the physiological state of the body.

The main issues facing nutritional biochemistry include:

What substances and in what quantities are necessary for the body to function?

What is the biofunction of each nutrient?

What are the consequences of consuming too much or not enough nutrients?

Power supplies the following functions:

plastic role - growth, development and renewal of body tissues;

energy supply to the cell;

intake of essential substances from food.

To satisfy all these functions, the diet must be complete and satisfy the principles rational nutrition, namely:

The calorie content of food should provide the body's energy expenditure, which depends on age, gender, type of physical or mental activity (for students it is 2200-3000 kcal/day).

The rational ratio of proteins, fats and carbohydrates, which for the average person is 1:1.5:4. Most of the food consists of carbohydrates, mainly of plant origin. A typical daily diet contains 400-500 g of carbohydrates, of which 60-80% are polysaccharides (mainly starch, in smaller quantities - glycogen and dietary fiber - fiber), 20-30% oligosaccharides (sucrose, lactose, maltose), the rest quantity – monosaccharides (glucose, fructose and pentoses). Saturated, monounsaturated and polyunsaturated fatty acids should be present in approximately equal proportions among dietary fats (100 g/day). The protein norm in the diet is from 80 to 100 g/day and it should be provided with proteins of both plant and animal origin (in equal shares).

The presence of essential components in food, many of which are present in minimal quantities (minor substances): essential amino acids, essential fatty acids (linoleic, linolenic, arachidonic), vitamins, microelements, fiber, aromatic components, essential oils, as well as water.

Meal regimen, which includes the frequency of intake and distribution of the daily diet morning-lunch-evening.

Compliance of the diet with the physiological (or pathological) status of the body (limitation of carbohydrates for diabetes mellitus, proteins for kidney pathology, lipids for atherosclerosis).

Food must be cooked to improve organoleptic properties and ensure safety for the body.

The main disturbances in the nutritional structure are as follows:

excessive consumption of animal fats;

deficiency of polyunsaturated fatty acids;

deficiency of complete (animal) proteins;

deficiency of most vitamins;

deficiency of mineral elements - calcium, iron;

deficiency of microelements - iodine, fluorine, selenium;

severe deficiency of dietary fiber.

Currently, it is widely used to correct the nutritional structure. dietary supplements(dietary supplement) to food. Dietary supplements are concentrates of natural or natural-identical biologically active substances intended for direct administration or inclusion in food products.

The use of dietary supplements allows you to eliminate the deficiency of essential nutrients, individualize a specific healthy or sick person depending on the needs and physiological state, increase the body’s nonspecific resistance, accelerate the binding and removal of xenobiotics from the body, and also specifically change the metabolism of toxic substances.

GENERAL CHARACTERISTICS OF MAIN FOOD COMPONENTS

Squirrels

The nutritional value of protein is ensured by the presence of essential amino acids, the hydrocarbon skeletons of which cannot be synthesized in the human body, and accordingly they must be supplied with food. They are also the main sources of nitrogen. The daily protein requirement is 80-100g, half of which should be of animal origin. Protein requirement is the amount of protein that meets all the metabolic needs of the body. In this case, the physiological state of the body, on the one hand, and, on the other hand, the properties of the food proteins themselves and the diet as a whole are necessarily taken into account. The properties of the components of the diet determine the digestion, absorption and metabolic utilization of amino acids.

Protein requirements have two components. The first must satisfy the need for total nitrogen, which ensures the biosynthesis of non-essential amino acids and other nitrogen-containing endogenous biologically active substances. Actually, the need for total nitrogen is the need for protein. The second component is determined by the human body’s need for essential amino acids that are not synthesized in the body. This is a specific part of the protein requirement, which is quantitatively included in the first component, but requires the consumption of protein of a certain quality, i.e. The carrier of total nitrogen must be proteins containing essential amino acids in a certain amount.

Animal proteins contain a full range of essential amino acids. However, along with a number of advantages, proteins also have disadvantages, the main of which are rather toxic catabolic products (ammonia, products of protein decay in the large intestine) and rather complex metabolic pathways.

Hormones play a vital role in many different processes that occur in the human body. They are necessary for growth and development, reproduction, metabolism and sexual function. The main suppliers of hormones to the body are the pituitary gland, pineal gland, thymus gland, thyroid gland, adrenal glands and pancreas. In addition, the testes in men and the ovaries in women produce hormones that are responsible for reproductive and sexual functions. If there is a deficiency of a hormone (such as testosterone, estrogen or cortisol), its level can be increased using various methods.

Steps

Increase testosterone levels

Determine if your testosterone levels are low. Consult your doctor if you have low sex drive, erection problems, depression, problems with concentration and memory. These symptoms may indicate low testosterone levels. Your doctor will be able to confirm low testosterone levels with a blood test.

Discuss the possibility of hormone therapy with your doctor. The syndrome of low testosterone is known as hypogonadism. If you are diagnosed with hypogonadism, your doctor may recommend replacement therapy. In this case, to maintain the level of the hormone in the body, a course of treatment with synthetic testosterone is prescribed.

• Never start taking testosterone without a doctor's recommendation, as the level of the hormone in the body should be carefully monitored during treatment. Too much testosterone is no better than too little testosterone.
• If hormone replacement therapy isn't right for you, you can turn to natural methods to increase testosterone levels.

1. Lose weight. Testosterone is a steroid hormone, meaning it dissolves in fat. Accordingly, if you are overweight, then part of the testosterone is stored in fatty tissues and does not participate in processes occurring in the body. This means that you may have enough testosterone in your body, but some of it is not providing any benefit. You can increase your testosterone levels naturally by simply losing weight.

   • The main cause of obesity is refined sugar. Avoid sugary drinks, processed and sugary foods.
   • Refined carbohydrates, which are found in baked goods, bagels, waffles, pretzels, ice cream, cookies, cakes, muffins, waffles, corn chips, potato chips, ketchup, and most other processed foods, are broken down into sugars fairly quickly in the body. Try to keep your consumption of these foods to a minimum.
   • Eat more vegetables. Vegetables slow down the absorption of sugar in the intestines and cleanse the body of harmful fats. Try to eat 5 servings of vegetables daily.

2. Engage in intense exercise. Intense exercise for a short period of time is more beneficial for raising testosterone levels than moderate and longer exercise. Such high-intensity exercise improves the functioning of testosterone receptors in the body. This helps the body produce enough testosterone without putting extra strain on the cells that secrete the hormone.

   • Warm up for three minutes before exercising. Then exercise as quickly and intensely as possible for 30 seconds. You can go swimming, cycling or running on a treadmill. After a 30-second peak, gradually slow down over 90 seconds.
   • Repeat the cycle of peak load and relaxation 7-8 times. The total duration of the workout should be 20 minutes.

3. Eat zinc. This trace element is necessary for sperm production and testosterone synthesis. It increases libido and maintains normal sexual function. Large amounts of zinc are found in meat, fish, unpasteurized milk, cheese, beans and yogurt. You can also take zinc supplements.

4. Maintain normal vitamin D levels. This vitamin is necessary for normal sperm quality and quantity. It also increases testosterone levels, which increases libido. Vitamin D is synthesized in the skin from cholesterol under the influence of ultraviolet radiation.

   • If you want to increase your vitamin D levels in your body, sunbathe. Spend 20-30 minutes in the sun so that the light hits your bare arms, legs, back and other parts of the body.
   • Fish and fish oil are also good sources of vitamin D.
   • Mushrooms contain large amounts of vitamin D.

5. Exercise in moderation. It has been found that intense exercise leads to a decrease in estrogen levels. Exercising for 30 minutes every day will help you maintain an optimal weight and prevent heart disease and other health problems, but longer sessions are not necessary. Try changing your exercise routine and/or reducing the intensity to increase estrogen levels in your body.

   • Intense exercise burns fat and, as a result, the body simply has nowhere to store estrogen. This is why female athletes sometimes experience irregular menstruation.
   • To maintain normal estrogen levels, you should limit yourself to moderate physical activity. Avoid intense workouts.

6. Eat a balanced diet. A healthy diet will help you maintain normal estrogen levels. In particular, avoid refined carbohydrates and sugar, which are found in foods such as baked goods, bagels, waffles, pretzels, and most other processed foods. Instead, eat foods rich in protein and dietary fiber.

   • Simple carbohydrates are quickly broken down in the body into glucose and other easily digestible sugars. This increases insulin resistance and interferes with the normal functioning of natural estrogen.
   • On the other hand, eating low-fat, high-fiber foods increases estrogen levels. Your diet should include plenty of fresh fruits and vegetables, especially those rich in dietary fiber.

7. Do not deny yourself the pleasure of eating foods rich in phytoestrogens. Phytoestrogens are natural substances whose effects are similar to those of estrogen. Phytoestrogens contained in food can serve as a good replacement for estrogen. Phytoestrogens are found in most plant foods, and the following foods are especially rich in them:

   • Soybeans, chickpeas, grain bran, peas, kidney beans, pinto beans, lima beans, flax seeds, legumes, vegetables and fruits. Try to eat 2-4 servings of these foods daily.
   • Keep it in moderation. Because phytoestrogens compete with estrogen receptors, excessive amounts of them can suppress estrogen production in the body.