Water-salt exchange. Water-salt metabolism Water-electrolyte metabolism biochemistry

The first living organisms appeared in water about 3 billion years ago, and to this day water is the main biosolvent.

Water is a liquid medium, which is the main component of a living organism, providing its vital physical and chemical processes: osmotic pressure, pH value, mineral composition. Water makes up on average 65% of the total body weight of an adult animal and more than 70% of a newborn. More than half of this water is inside the cells of the body. Given the very small molecular weight of water, it is calculated that about 99% of all molecules in the cell are water molecules (Bohinski R., 1987).

The high heat capacity of water (1 cal required to heat 1 g of water by 1°C) allows the body to absorb a significant amount of heat without a significant increase in core temperature. Due to the high heat of water evaporation (540 cal/g), the body dissipates part of the heat energy, avoiding overheating.

Water molecules are characterized by strong polarization. In a water molecule, each hydrogen atom forms an electron pair with the central oxygen atom. Therefore, the water molecule has two permanent dipoles, since the high electron density near oxygen gives it a negative charge, while each hydrogen atom is characterized by a reduced electron density and carries a partial positive charge. As a result, electrostatic bonds arise between the oxygen atom of one water molecule and the hydrogen of another molecule, called hydrogen bonds. This structure of water explains its high heat of vaporization and boiling point.

Hydrogen bonds are relatively weak. Their dissociation energy (bond breaking energy) in liquid water is 23 kJ/mol, compared to 470 kJ for an O-H covalent bond in a water molecule. The lifetime of a hydrogen bond is from 1 to 20 picoseconds (1 picosecond = 1(G 12 s). However, hydrogen bonds are not unique to water. They can also occur between a hydrogen atom and nitrogen in other structures.

In the state of ice, each water molecule forms a maximum of four hydrogen bonds, forming a crystal lattice. In contrast, in liquid water at room temperature, each water molecule has hydrogen bonds with an average of 3-4 other water molecules. This crystal structure of ice makes it less dense than liquid water. Therefore, ice floats on the surface of liquid water, protecting it from freezing.

Thus, hydrogen bonds between water molecules provide the binding forces that keep water in liquid form at room temperature and transform the molecules into ice crystals. Note that, in addition to hydrogen bonds, biomolecules are characterized by other types of non-covalent bonds: ionic, hydrophobic, and van der Waals forces, which are individually weak, but together have a strong effect on the structures of proteins, nucleic acids, polysaccharides, and cell membranes.

Water molecules and their ionization products (H + and OH) have a pronounced effect on the structures and properties of cell components, including nucleic acids, proteins, and fats. In addition to stabilizing the structure of proteins and nucleic acids, hydrogen bonds are involved in the biochemical expression of genes.

As the basis of the internal environment of cells and tissues, water determines their chemical activity, being a unique solvent for various substances. Water increases the stability of colloidal systems, participates in numerous reactions of hydrolysis and hydrogenation in oxidation processes. Water enters the body with feed and drinking water.

Many metabolic reactions in tissues lead to the formation of water, which is called endogenous (8-12% of the total body fluid). The sources of endogenous water of the body are primarily fats, carbohydrates, proteins. So the oxidation of 1 g of fats, carbohydrates and proteins leads to the formation of 1.07; 0.55 and 0.41 g of water, respectively. Therefore, animals in the desert can do without water for some time (camels even for quite a long time). The dog dies without drinking water after 10 days, and without food - after a few months. The loss of 15-20% of water by the body leads to the death of the animal.

The low viscosity of water determines the constant redistribution of fluid within the organs and tissues of the body. Water enters the gastrointestinal tract, and then almost all of this water is absorbed back into the blood.

Transport of water through cell membranes is carried out quickly: 30-60 minutes after ingestion of water, the animal sets in a new osmotic equilibrium between the extracellular and intracellular fluid of tissues. The volume of extracellular fluid has a great influence on blood pressure; an increase or decrease in the volume of extracellular fluid leads to disturbances in blood circulation.

An increase in the amount of water in the tissues (hyperhydria) occurs with a positive water balance (excess water intake in violation of the regulation of water-salt metabolism). Hyperhydria leads to the accumulation of fluid in the tissues (edema). Dehydration of the body is noted with a lack of drinking water or with excess fluid loss (diarrhea, bleeding, increased sweating, hyperventilation of the lungs). The loss of water by animals occurs due to the surface of the body, the digestive system, respiration, urinary tract, milk in lactating animals.

The exchange of water between blood and tissues occurs due to the difference in hydrostatic pressure in the arterial and venous circulatory system, as well as due to the difference in oncotic pressure in the blood and tissues. Vasopressin, a hormone from the posterior pituitary gland, retains water in the body by reabsorbing it in the renal tubules. Aldosterone, a hormone of the adrenal cortex, ensures the retention of sodium in the tissues, and water is stored with it. An animal's need for water is on average 35-40 g per kg of body weight per day.

Note that the chemicals in the animal body are in ionized form, in the form of ions. Ions, depending on the sign of the charge, refer to anions (negatively charged ion) or cations (positively charged ion). Elements that dissociate in water to form anions and cations are classified as electrolytes. Alkali metal salts (NaCl, KC1, NaHC0 3), salts of organic acids (sodium lactate, for example) dissociate completely when dissolved in water and are electrolytes. Easily soluble in water, sugars and alcohols do not dissociate in water and do not carry a charge, therefore they are considered as non-electrolytes. The sum of anions and cations in body tissues is generally the same.

Ions of dissociating substances, having a charge, are oriented around water dipoles. The water dipoles surround the cations with their negative charges, while the anions are surrounded by the positive charges of water. In this case, the phenomenon of electrostatic hydration occurs. Due to hydration, this part of the water in the tissues is in a bound state. Another part of the water is associated with various cellular organelles, making up the so-called immobile water.

Body tissues include 20 mandatory of all natural chemical elements. Carbon, oxygen, hydrogen, nitrogen, sulfur are indispensable components of biomolecules, of which oxygen predominates by mass.

Chemical elements in the body form salts (minerals) and are part of biologically active molecules. Biomolecules have a low molecular weight (30-1500) or are macromolecules (proteins, nucleic acids, glycogen) with molecular weights of millions of units. Individual chemical elements (Na, K, Ca, S, P, C1) make up about 10 - 2% or more in tissues (macroelements), while others (Fe, Co, Cu, Zn, J, Se, Ni, Mo) , for example, are present in much smaller quantities - 10 "3 -10 ~ 6% (trace elements). In the body of an animal, minerals make up 1-3% of the total body weight and are distributed extremely unevenly. In some organs, the content of trace elements can be significant, for example, iodine in the thyroid gland.

After the absorption of minerals to a greater extent in the small intestine, they enter the liver, where some of them are deposited, while others are distributed to various organs and tissues of the body. Minerals are excreted from the body mainly in the composition of urine and feces.

The exchange of ions between cells and intercellular fluid occurs on the basis of both passive and active transport through semipermeable membranes. The resulting osmotic pressure causes cell turgor, maintaining the elasticity of tissues and the shape of organs. Active transport of ions or their movement into an environment with a lower concentration (against the osmotic gradient) requires the expenditure of energy of ATP molecules. Active ion transport is characteristic of Na + , Ca 2 ~ ions and is accompanied by an increase in oxidative processes that generate ATP.

The role of minerals is to maintain a certain osmotic pressure of blood plasma, acid-base balance, permeability of various membranes, regulation of enzyme activity, preservation of biomolecular structures, including proteins and nucleic acids, in maintaining the motor and secretory functions of the digestive tract. Therefore, for many violations of the functions of the digestive tract of an animal, various compositions of mineral salts are recommended as therapeutic agents.

Both the absolute quantity and the proper ratio in the tissues between certain chemical elements are important. In particular, the optimal ratio in the tissues of Na:K:Cl is normally 100:1:1.5. A pronounced feature is the "asymmetry" in the distribution of salt ions between the cell and the extracellular environment of body tissues.

Department of Biochemistry

I approve

Head cafe prof., d.m.s.

Meshchaninov V.N.

______''_____________2006

LECTURE #25

Topic: Water-salt and mineral metabolism

Faculties: medical and preventive, medical and preventive, pediatric.

Water-salt exchange- exchange of water and basic electrolytes of the body (Na +, K +, Ca 2+, Mg 2+, Cl -, HCO 3 -, H 3 PO 4).

electrolytes- substances that dissociate in solution into anions and cations. They are measured in mol/l.

Non-electrolytes- substances that do not dissociate in solution (glucose, creatinine, urea). They are measured in g / l.

Mineral exchange- the exchange of any mineral components, including those that do not affect the main parameters of the liquid medium in the body.

Water- the main component of all body fluids.

The biological role of water

Water is a universal solvent for most organic (except lipids) and inorganic compounds.
Water and substances dissolved in it create the internal environment of the body.
Water provides the transport of substances and thermal energy throughout the body.
A significant part of the chemical reactions of the body takes place in the aqueous phase.
Water is involved in the reactions of hydrolysis, hydration, dehydration.
Determines the spatial structure and properties of hydrophobic and hydrophilic molecules.
In complex with GAG, water performs a structural function.

GENERAL PROPERTIES OF BODY LIQUIDS

All body fluids are characterized by common properties: volume, osmotic pressure and pH value.

Volume. In all terrestrial animals, fluid makes up about 70% of body weight.

The distribution of water in the body depends on age, gender, muscle mass, physique and fat content. The water content in various tissues is distributed as follows: lungs, heart and kidneys (80%), skeletal muscles and brain (75%), skin and liver (70%), bones (20%), adipose tissue (10%). In general, lean people have less fat and more water. In men, water accounts for 60%, in women - 50% of body weight. Older people have more fat and less muscle. On average, the body of men and women over 60 years of age contains 50% and 45% water, respectively.

With complete deprivation of water, death occurs after 6-8 days, when the amount of water in the body decreases by 12%.

All body fluid is divided into intracellular (67%) and extracellular (33%) pools.

extracellular pool(extracellular space) consists of:

1. Intravascular fluid;

2. Interstitial fluid (intercellular);

3. Transcellular fluid (fluid of the pleural, pericardial, peritoneal cavities and synovial space, cerebrospinal and intraocular fluid, secretion of sweat, salivary and lacrimal glands, secretion of the pancreas, liver, gallbladder, gastrointestinal tract and respiratory tract).

Between the pools, liquids are intensively exchanged. The movement of water from one sector to another occurs when the osmotic pressure changes.

Osmotic pressure - This is the pressure exerted by all the substances dissolved in water. The osmotic pressure of the extracellular fluid is determined mainly by the concentration of NaCl.

Extracellular and intracellular fluids differ significantly in composition and concentration of individual components, but the total total concentration of osmotically active substances is approximately the same.

pH is the negative decimal logarithm of the proton concentration. The pH value depends on the intensity of the formation of acids and bases in the body, their neutralization by buffer systems and removal from the body with urine, exhaled air, sweat and feces.

Depending on the characteristics of metabolism, the pH value can differ markedly both inside the cells of different tissues and in different compartments of the same cell (neutral acidity in the cytosol, strongly acidic in lysosomes and in the intermembrane space of mitochondria). In the intercellular fluid of various organs and tissues and blood plasma, the pH value, as well as the osmotic pressure, is a relatively constant value.

REGULATION OF THE WATER-SALT BALANCE OF THE BODY

In the body, the water-salt balance of the intracellular environment is maintained by the constancy of the extracellular fluid. In turn, the water-salt balance of the extracellular fluid is maintained through the blood plasma with the help of organs and is regulated by hormones.

Bodies regulating water-salt metabolism

The intake of water and salts into the body occurs through the gastrointestinal tract, this process is controlled by thirst and salt appetite. Removal of excess water and salts from the body is carried out by the kidneys. In addition, water is removed from the body by the skin, lungs and gastrointestinal tract.

Water balance in the body

For the gastrointestinal tract, skin and lungs, the excretion of water is a side process that occurs as a result of their main functions. For example, the gastrointestinal tract loses water when undigested substances, metabolic products and xenobiotics are excreted from the body. The lungs lose water during respiration, and the skin during thermoregulation.

Changes in the work of the kidneys, skin, lungs and gastrointestinal tract can lead to a violation of water-salt homeostasis. For example, in a hot climate, to maintain body temperature, the skin increases sweating, and in case of poisoning, vomiting or diarrhea occurs from the gastrointestinal tract. As a result of increased dehydration and loss of salts in the body, a violation of the water-salt balance occurs.

Hormones that regulate water-salt metabolism

Vasopressin

Antidiuretic hormone (ADH), or vasopressin- a peptide with a molecular weight of about 1100 D, containing 9 AAs connected by one disulfide bridge.

ADH is synthesized in the neurons of the hypothalamus and transported to the nerve endings of the posterior pituitary gland (neurohypophysis).

The high osmotic pressure of the extracellular fluid activates the osmoreceptors of the hypothalamus, resulting in nerve impulses that are transmitted to the posterior pituitary gland and cause the release of ADH into the bloodstream.

ADH acts through 2 types of receptors: V 1 and V 2 .

The main physiological effect of the hormone is realized by V 2 receptors, which are located on the cells of the distal tubules and collecting ducts, which are relatively impermeable to water molecules.

ADH through V 2 receptors stimulates the adenylate cyclase system, as a result, proteins are phosphorylated that stimulate the expression of the membrane protein gene - aquaporina-2 . Aquaporin-2 is embedded in the apical membrane of cells, forming water channels in it. Through these channels, water is reabsorbed by passive diffusion from the urine into the interstitial space and the urine is concentrated.

In the absence of ADH, urine is not concentrated (density<1010г/л) и может выделяться в очень больших количествах (>20l/day), which leads to dehydration of the body. This state is called diabetes insipidus .

The cause of ADH deficiency and diabetes insipidus are: genetic defects in the synthesis of prepro-ADH in the hypothalamus, defects in the processing and transport of proADH, damage to the hypothalamus or neurohypophysis (eg, as a result of traumatic brain injury, tumor, ischemia). Nephrogenic diabetes insipidus occurs due to a mutation in the type V 2 ADH receptor gene.

V 1 receptors are localized in the membranes of SMC vessels. ADH through V 1 receptors activates the inositol triphosphate system and stimulates the release of Ca 2+ from the ER, which stimulates the contraction of SMC vessels. The vasoconstrictive effect of ADH is seen at high concentrations of ADH.

Concentration calcium in the extracellular fluid is normally maintained at a strictly constant level, rarely increasing or decreasing by several percent relative to the normal values of 9.4 mg / dl, which is equivalent to 2.4 mmol of calcium per liter. Such strict control is very important in connection with the main role of calcium in many physiological processes, including contraction of skeletal, cardiac and smooth muscles, blood coagulation, transmission of nerve impulses. Excitable tissues, including the nervous one, are very sensitive to changes in calcium concentration, and an increase in the concentration of calcium ions compared to the norm (hypscalcemia) causes an increasing damage to the nervous system; on the contrary, a decrease in the concentration of calcium (hypocalcemia) increases the excitability of the nervous system.

An important feature of the regulation of the concentration of extracellular calcium: only about 0.1% of the total amount of calcium in the body is present in the extracellular fluid, about 1% is inside the cells, and the rest is stored in the bones, so the bones can be considered as a large store of calcium that releases it into extracellular space, if the concentration of calcium there decreases, and, on the contrary, taking away excess calcium for storage.

Approximately 85% phosphates of the organism is stored in the bones, 14 to 15% - in the cells, and only less than 1% is present in the extracellular fluid. The concentration of phosphates in the extracellular fluid is not as strictly regulated as the concentration of calcium, although they perform a variety of important functions, controlling many processes together with calcium.

Absorption of calcium and phosphates in the intestine and their excretion in the feces. The usual rate of intake of calcium and phosphate is approximately 1000 mg/day, which corresponds to the amount extracted from 1 liter of milk. In general, divalent cations such as ionized calcium are poorly absorbed in the gut. However, as discussed below, vitamin D promotes intestinal absorption of calcium, and nearly 35% (about 350 mg/day) of calcium ingested is absorbed. The remaining calcium in the intestine enters the feces and is removed from the body. Additionally, about 250 mg / day of calcium enters the intestines as part of digestive juices and desquamated cells. Thus, about 90% (900 mg/day) of the daily intake of calcium is excreted in the feces.

hypocalcemia causes excitation of the nervous system and tetany. If the concentration of calcium ions in the extracellular fluid falls below normal values, the nervous system gradually becomes more and more excitable, because. this change leads to an increase in sodium ion permeability, facilitating action potential generation. In the event of a drop in the concentration of calcium ions to a level of 50% of the norm, the excitability of peripheral nerve fibers becomes so great that they begin to spontaneously discharge.

Hypercalcemia reduces the excitability of the nervous system and muscle activity. If the concentration of calcium in the liquid media of the body exceeds the norm, the excitability of the nervous system decreases, which is accompanied by a slowdown in reflex responses. An increase in calcium concentration leads to a decrease in the QT interval on the electrocardiogram, a decrease in appetite and constipation, possibly due to a decrease in the contractile activity of the muscular wall of the gastrointestinal tract.

These depressive effects begin to appear when the calcium level rises above 12 mg/dl and become noticeable when the calcium level exceeds 15 mg/dl.

The resulting nerve impulses reach the skeletal muscles, causing tetanic contractions. Therefore, hypocalcemia causes tetany, sometimes it provokes epileptiform seizures, since hypocalcemia increases the excitability of the brain.

Absorption of phosphates in the intestine is easy. In addition to those amounts of phosphate that are excreted in the feces in the form of calcium salts, almost all phosphate contained in the daily diet is absorbed from the intestine into the blood and then excreted in the urine.

Excretion of calcium and phosphate by the kidney. Approximately 10% (100 mg/day) of calcium ingested is excreted in the urine, about 41% of plasma calcium is bound to proteins and therefore is not filtered from glomerular capillaries. The remaining amount is combined with anions, such as phosphates (9%), or ionized (50%) and filtered by the glomerulus into the renal tubules.

Normally, 99% of the filtered calcium is reabsorbed in the tubules of the kidney, so almost 100 mg of calcium is excreted in the urine per day. Approximately 90% of the calcium contained in the glomerular filtrate is reabsorbed in the proximal tubule, the loop of Henle, and at the beginning of the distal tubule. The remaining 10% calcium is then reabsorbed at the end of the distal tubule and at the beginning of the collecting ducts. Reabsorption becomes highly selective and depends on the concentration of calcium in the blood.

If the concentration of calcium in the blood is low, reabsorption increases, as a result, almost no calcium is lost in the urine. On the contrary, when the concentration of calcium in the blood slightly exceeds normal values, calcium excretion increases significantly. The most important factor controlling calcium reabsorption in the distal nephron and therefore regulating the level of calcium excretion is parathyroid hormone.

Renal phosphate excretion is regulated by a copious flux mechanism. This means that when the plasma phosphate concentration drops below a critical value (about 1 mmol/l), all phosphate from the glomerular filtrate is reabsorbed and ceases to be excreted in the urine. But if the concentration of phosphate exceeds the normal value, its loss in the urine is directly proportional to the additional increase in its concentration. The kidneys regulate the concentration of phosphate in the extracellular space, changing the rate of excretion of phosphate in accordance with their concentration in plasma and the rate of phosphate filtration in the kidney.

However, as we will see below, parathormone can significantly increase renal phosphate excretion, so it plays an important role in the regulation of plasma phosphate concentration along with the control of calcium concentration. Parathormone is a powerful regulator of the concentration of calcium and phosphate, exercising its influence by controlling the processes of reabsorption in the intestine, excretion in the kidney and the exchange of these ions between the extracellular fluid and bone.

Excessive activity of the parathyroid glands causes a rapid leaching of calcium salts from the bones, followed by the development of hypercalcemia in the extracellular fluid; on the contrary, hypofunction of the parathyroid glands leads to hypocalcemia, often with the development of tetany.

Functional anatomy of the parathyroid glands. Normally, a person has four parathyroid glands. They are located immediately after the thyroid gland, in pairs at its upper and lower poles. Each parathyroid gland is a formation about 6 mm long, 3 mm wide and 2 mm high.

Macroscopically, the parathyroid glands look like dark brown fat, it is difficult to determine their location during thyroid surgery, because. they often look like an extra lobe of the thyroid gland. That is why, until the moment when the importance of these glands was established, total or subtotal thyroidectomy ended with the simultaneous removal of the parathyroid glands.

Removal of half of the parathyroid glands does not cause serious physiological disorders, removal of three or all four glands leads to transient hypoparathyroidism. But even a small amount of the remaining parathyroid tissue is able to ensure the normal function of the parathyroid glands due to hyperplasia.

The adult parathyroid glands consist predominantly of chief cells and more or less oxyphilic cells, which are absent in many animals and young people. Chief cells presumably secrete most, if not all, of the parathyroid hormone, and in oxyphilic cells, their purpose.

It is believed that they are a modification or depleted form of the main cells that no longer synthesize the hormone.

Chemical structure of parathyroid hormone. PTH was isolated in a purified form. Initially, it is synthesized on ribosomes as a preprohormone, a polypeptide chain of PO amino acid residues. Then it is cleaved to a prohormone, consisting of 90 amino acid residues, then to the stage of a hormone, which includes 84 amino acid residues. This process is carried out in the endoplasmic reticulum and the Golgi apparatus.

As a result, the hormone is packaged into secretory granules in the cytoplasm of cells. The final form of the hormone has a molecular weight of 9500; smaller compounds, consisting of 34 amino acid residues, adjacent to the N-terminus of the parathyroid hormone molecule, also isolated from the parathyroid glands, have full PTH activity. It has been established that the kidneys completely excrete the form of the hormone, consisting of 84 amino acid residues, very quickly, within a few minutes, while the remaining numerous fragments maintain a high degree of hormonal activity for a long time.

Thyrocalcitonin- a hormone produced in mammals and in humans by parafollicular cells of the thyroid gland, parathyroid gland and thymus gland. In many animals, for example, fish, a hormone similar in function is produced not in the thyroid gland (although all vertebrates have it), but in ultimobranchial bodies and therefore is simply called calcitonin. Thyrocalcitonin is involved in the regulation of phosphorus-calcium metabolism in the body, as well as the balance of osteoclast and osteoblast activity, a functional parathyroid hormone antagonist. Thyrocalcitonin lowers the content of calcium and phosphate in the blood plasma by increasing the uptake of calcium and phosphate by osteoblasts. It also stimulates the reproduction and functional activity of osteoblasts. At the same time, thyrocalcitonin inhibits the reproduction and functional activity of osteoclasts and the processes of bone resorption. Thyrocalcitonin is a protein-peptide hormone with a molecular weight of 3600. Enhances the deposition of phosphorus-calcium salts on the collagen matrix of bones. Thyrocalcitonin, like parathyroid hormone, enhances phosphaturia.

Calcitriol

Structure: It is a derivative of vitamin D and belongs to steroids.

Synthesis: Cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) formed in the skin under the action of ultraviolet radiation and supplied with food are hydroxylated in the liver at C25 and in the kidneys at C1. As a result, 1,25-dioxycalciferol (calcitriol) is formed.

Regulation of synthesis and secretion

Activate: Hypocalcemia increases hydroxylation at C1 in the kidneys.

Reduce: Excess calcitriol inhibits C1 hydroxylation in the kidneys.

Mechanism of action: Cytosolic.

Targets and effects: The effect of calcitriol is to increase the concentration of calcium and phosphorus in the blood:

in the intestine it induces the synthesis of proteins responsible for the absorption of calcium and phosphates, in the kidneys it increases the reabsorption of calcium and phosphates, in the bone tissue it increases calcium resorption. Pathology: Hypofunction Corresponds to the picture of hypovitaminosis D. Role 1.25-dihydroxycalciferol in the exchange of Ca and P

Vitamin D (calciferol, antirachitic)

Sources: There are two sources of vitamin D:

liver, yeast, fatty milk products (butter, cream, sour cream), egg yolk,

is formed in the skin under ultraviolet irradiation from 7-dehydrocholesterol in an amount of 0.5-1.0 μg / day.

Daily requirement: For children - 12-25 mcg or 500-1000 IU, in adults the need is much less.

WITH
tripling: Vitamin is presented in two forms - ergocalciferol and cholecalciferol. Chemically, ergocalciferol differs from cholecalciferol by the presence of a double bond between C22 and C23 and a methyl group at C24 in the molecule.

After absorption in the intestines or after synthesis in the skin, the vitamin enters the liver. Here it is hydroxylated at C25 and transported by the calciferol transport protein to the kidneys, where it is hydroxylated again, already at C1. 1,25-dihydroxycholecalciferol or calcitriol is formed. The hydroxylation reaction in the kidneys is stimulated by parathormone, prolactin, growth hormone and suppressed by high concentrations of phosphate and calcium.

Biochemical functions: 1. An increase in the concentration of calcium and phosphate in the blood plasma. For this, calcitriol: stimulates the absorption of Ca2+ and phosphate ions in the small intestine (main function), stimulates the reabsorption of Ca2+ and phosphate ions in the proximal renal tubules.

2. In bone tissue, the role of vitamin D is twofold:

stimulates the release of Ca2+ ions from the bone tissue, as it promotes the differentiation of monocytes and macrophages into osteoclasts and a decrease in the synthesis of type I collagen by osteoblasts,

increases the mineralization of the bone matrix, as it increases the production of citric acid, which forms insoluble salts with calcium here.

3. Participation in immune reactions, in particular in the stimulation of pulmonary macrophages and in the production of nitrogen-containing free radicals by them, which are destructive, including for Mycobacterium tuberculosis.

4. Suppresses the secretion of parathyroid hormone by increasing the concentration of calcium in the blood, but enhances its effect on calcium reabsorption in the kidneys.

Hypovitaminosis. Acquired hypovitaminosis. Cause.

It often occurs with nutritional deficiencies in children, with insufficient insolation in people who do not go out, or with national clothing patterns. Also, the cause of hypovitaminosis can be a decrease in hydroxylation of calciferol (liver and kidney disease) and impaired absorption and digestion of lipids (celiac disease, cholestasis).

Clinical picture: In children from 2 to 24 months, it manifests itself in the form of rickets, in which, despite intake from food, calcium is not absorbed in the intestines, but is lost in the kidneys. This leads to a decrease in the concentration of calcium in the blood plasma, a violation of the mineralization of bone tissue and, as a result, to osteomalacia (softening of the bone). Osteomalacia is manifested by deformation of the bones of the skull (tuberosity of the head), chest (chicken breast), curvature of the lower leg, rickets on the ribs, an increase in the abdomen due to muscle hypotension, teething and overgrowth of fontanelles slows down.

In adults, osteomalacia is also observed, i.e. osteoid continues to be synthesized but not mineralized. The development of osteoporosis is also partly associated with vitamin D deficiency.

Hereditary hypovitaminosis

Vitamin D-dependent type I hereditary rickets, in which there is a recessive defect in renal α1-hydroxylase. Manifested by developmental delay, rickety features of the skeleton, etc. Treatment is calcitriol preparations or large doses of vitamin D.

Vitamin D-dependent hereditary type II rickets, in which there is a defect in tissue calcitriol receptors. Clinically, the disease is similar to type I, but alopecia, milia, epidermal cysts, and muscle weakness are additionally noted. Treatment varies depending on the severity of the disease, but large doses of calciferol help.

Hypervitaminosis. Cause

Excess consumption with drugs (at least 1.5 million IU per day).

Clinical picture: Early signs of a vitamin D overdose are nausea, headache, loss of appetite and body weight, polyuria, thirst, and polydipsia. There may be constipation, hypertension, muscle rigidity. Chronic excess of vitamin D leads to hypervitaminosis, which is noted: demineralization of bones, leading to their fragility and fractures. an increase in the concentration of calcium and phosphorus ions in the blood, leading to calcification of blood vessels, lung tissue and kidneys.

Dosage forms

Vitamin D - fish oil, ergocalciferol, cholecalciferol.

1,25-Dioxycalciferol (active form) - osteotriol, oxidevit, rocaltrol, forkal plus.

58. Hormones, derivatives of fatty acids. Synthesis. Functions.

By chemical nature, hormonal molecules are classified into three groups of compounds:

1) proteins and peptides; 2) derivatives of amino acids; 3) steroids and derivatives of fatty acids.

Eicosanoids (είκοσι, Greek-twenty) include oxidized derivatives of eicosan acids: eicosotriene (C20:3), arachidonic (C20:4), timnodonic (C20:5) well-x to-t. The activity of eicosanoids differs significantly from the number of double bonds in the molecule, which depends on the structure of the original x-th to-s. Eicosanoids are called hormone-like things, because. they can only have a local effect, remaining in the blood for several seconds. Obr-Xia in all organs and tissues in almost all types of cells. Eicosanoids cannot be deposited, they are destroyed within a few seconds, and therefore the cell must synthesize them constantly from the incoming ω6- and ω3-series fatty acids. There are three main groups:

Prostaglandins (Pg)- are synthesized in almost all cells, except for erythrocytes and lymphocytes. There are types of prostaglandins A, B, C, D, E, F. The functions of prostaglandins are reduced to a change in the tone of the smooth muscles of the bronchi, the genitourinary and vascular systems, the gastrointestinal tract, while the direction of the changes is different depending on the type of prostaglandins, cell type and conditions . They also affect body temperature. Can activate adenylate cyclase Prostacyclins are a subspecies of prostaglandins (Pg I), cause dilatation of small vessels, but still have a special function - they inhibit platelet aggregation. Their activity increases with an increase in the number of double bonds. Synthesized in the endothelium of the vessels of the myocardium, uterus, gastric mucosa. Thromboxanes (Tx) formed in platelets, stimulate their aggregation and cause vasoconstriction. Their activity decreases with an increase in the number of double bonds. Increase the activity of phosphoinositide metabolism Leukotrienes (Lt) synthesized in leukocytes, in the cells of the lungs, spleen, brain, heart. There are 6 types of leukotrienes A, B, C, D, E, F. In leukocytes, they stimulate mobility, chemotaxis and cell migration to the focus of inflammation; in general, they activate inflammation reactions, preventing its chronicity. They also cause contraction of the muscles of the bronchi (in doses 100-1000 times less than histamine). increase the permeability of membranes for Ca2+ ions. Since cAMP and Ca 2+ ions stimulate the synthesis of eicosanoids, a positive feedback is closed in the synthesis of these specific regulators.

AND
source free eicosanoic acids are cell membrane phospholipids. Under the influence of specific and non-specific stimuli, phospholipase A 2 or a combination of phospholipase C and DAG-lipase are activated, which cleave a fatty acid from the C2 position of phospholipids.

P

Olineunsaturated well-I to-that metabolizes mainly in 2 ways: cyclooxygenase and lipoxygenase, the activity of which in different cells is expressed to varying degrees. The cyclooxygenase pathway is responsible for the synthesis of prostaglandins and thromboxanes, while the lipoxygenase pathway is responsible for the synthesis of leukotrienes.

Biosynthesis most eicosanoids begins with the cleavage of arachidonic acid from a membrane phospholipid or diacylglycerol in the plasma membrane. The synthetase complex is a polyenzymatic system that functions mainly on EPS membranes. Arr-Xia eicosanoids easily penetrate through the plasma membrane of cells, and then through the intercellular space are transferred to neighboring cells or exit into the blood and lymph. The rate of synthesis of eicosanoids increased under the influence of hormones and neurotransmitters, the act of their adenylate cyclase or increasing the concentration of Ca 2+ ions in cells. The most intense sample of prostaglandins occurs in the testes and ovaries. In many tissues, cortisol inhibits the absorption of arachidonic acid, which leads to the suppression of eicosanoids, and thereby has an anti-inflammatory effect. Prostaglandin E1 is a powerful pyrogen. The suppression of the synthesis of this prostaglandin explains the therapeutic effect of aspirin. The half-life of eicosanoids is 1-20 s. Enzymes that inactivate them are present in all tissues, but the greatest number of them is in the lungs. Lek-I reg-I synthesis: Glucocorticoids, indirectly through the synthesis of specific proteins, block the synthesis of eicosanoids by reducing the binding of phospholipids by phospholipase A 2, which prevents the release of polyunsaturated to-you from the phospholipid. Non-steroidal anti-inflammatory drugs (aspirin, indomethacin, ibuprofen) irreversibly inhibit cyclooxygenase and reduce the production of prostaglandins and thromboxanes.

60. Vitamins E. K and ubiquinone, their participation in metabolism.

E vitamins (tocopherols). The name "tocopherol" of vitamin E comes from the Greek "tokos" - "birth" and "ferro" - to wear. It was found in oil from germinated wheat grains. Currently known family of tocopherols and tocotrienols found in natural sources. All of them are metal derivatives of the original tokol compound, they are very similar in structure and are denoted by the letters of the Greek alphabet. α-tocopherol exhibits the highest biological activity.

Tocopherol is insoluble in water; like vitamins A and D, it is fat soluble, resistant to acids, alkalis and high temperatures. Normal boiling has almost no effect on it. But light, oxygen, ultraviolet rays or chemical oxidizing agents are detrimental.

V vitamin E contains Ch. arr. in lipoprotein membranes of cells and subcellular organelles, where it is localized due to the intermol. interaction with unsaturated fatty acids. His biol. activity based on the ability to form stable free. radicals as a result of the elimination of the H atom from the hydroxyl group. These radicals can interact. with free radicals involved in the formation of org. peroxides. Thus, vitamin E prevents the oxidation of unsaturated. lipids also protects from destruction biol. membranes and other molecules such as DNA.

Tocopherol increases the biological activity of vitamin A, protecting the unsaturated side chain from oxidation.

Sources: for humans - vegetable oils, lettuce, cabbage, cereal seeds, butter, egg yolk.

daily requirement an adult in the vitamin is about 5 mg.

Clinical manifestations of insufficiency in humans are not fully understood. The positive effect of vitamin E is known in the treatment of violations of the fertilization process, with repeated involuntary abortions, some forms of muscle weakness and dystrophy. The use of vitamin E for premature babies and children who are bottle-fed is shown, since cow's milk contains 10 times less vitamin E than women's milk. Vitamin E deficiency is manifested by the development of hemolytic anemia, possibly due to the destruction of erythrocyte membranes as a result of LPO.

At
BIQUINONS (coenzymes Q) is a widespread substance and has been found in plants, fungi, animals, and m/o. It belongs to the group of fat-soluble vitamin-like compounds, it is poorly soluble in water, but is destroyed when exposed to oxygen and high temperatures. In the classical sense, ubiquinone is not a vitamin, as it is synthesized in sufficient quantities in the body. But in some diseases, the natural synthesis of coenzyme Q decreases and it is not enough to meet the need, then it becomes an indispensable factor.

At
biquinones play an important role in the cell bioenergetics of most prokaryotes and all eukaryotes. Main function of ubiquinones - transfer of electrons and protons from decomp. substrates to cytochromes during respiration and oxidative phosphorylation. Ubiquinones, ch. arr. in reduced form (ubiquinols, Q n H 2), perform the function of antioxidants. May be prosthetic. a group of proteins. Three classes of Q-binding proteins have been identified that act in respiration. chains at the sites of functioning of the enzymes succinate-biquinone reductase, NADH-ubiquinone reductase and cytochromes b and c 1.

In the process of electron transfer from NADH dehydrogenase through FeS to ubiquinone, it is reversibly converted to hydroquinone. Ubiquinone acts as a collector by accepting electrons from NADH dehydrogenase and other flavin dependent dehydrogenases, in particular from succinate dehydrogenase. Ubiquinone is involved in reactions such as:

E (FMNH 2) + Q → E (FMN) + QH 2.

Deficiency symptoms: 1) anemia 2) changes in the skeletal muscles 3) heart failure 4) changes in the bone marrow

Overdose symptoms: possible only with excessive administration and is usually manifested by nausea, stool disorders and abdominal pain.

Sources: Vegetable - Wheat germ, vegetable oils, nuts, cabbage. Animals - Liver, heart, kidney, beef, pork, fish, eggs, chicken. Synthesized by intestinal microflora.

WITH
weft requirement: It is believed that under normal conditions the body covers the need completely, but there is an opinion that this required daily amount is 30-45 mg.

Structural formulas of the working part of the coenzymes FAD and FMN. During the reaction, FAD and FMN gain 2 electrons and, unlike NAD+, both lose a proton from the substrate.

63. Vitamins C and P, structure, role. Scurvy.

Vitamin P(bioflavonoids; rutin, citrine; permeability vitamin)

It is now known that the concept of "vitamin P" combines the family of bioflavonoids (catechins, flavonones, flavones). This is a very diverse group of plant polyphenolic compounds that affect vascular permeability in a similar way to vitamin C.

The term "vitamin P", which increases the resistance of capillaries (from Latin permeability - permeability), combines a group of substances with similar biological activity: catechins, chalcones, dihydrochalcones, flavins, flavonones, isoflavones, flavonols, etc. All of them have P-vitamin activity , and their structure is based on the diphenylpropane carbon “skeleton” of a chromone or flavone. This explains their common name "bioflavonoids".

Vitamin P is absorbed better in the presence of ascorbic acid, and high temperatures easily destroy it.

AND sources: lemons, buckwheat, chokeberry, blackcurrant, tea leaves, rose hips.

daily requirement for a person It is, depending on lifestyle, 35-50 mg per day.

Biological role flavonoids is to stabilize the intercellular matrix of connective tissue and reduce capillary permeability. Many representatives of the vitamin P group have a hypotensive effect.

-Vitamin P "protects" hyaluronic acid, which strengthens the walls of blood vessels and is the main component of the biological lubrication of the joints, from the destructive action of hyaluronidase enzymes. Bioflavonoids stabilize the basic substance of the connective tissue by inhibiting hyaluronidase, which is confirmed by data on the positive effect of P-vitamin preparations, as well as ascorbic acid, in the prevention and treatment of scurvy, rheumatism, burns, etc. These data indicate a close functional relationship between vitamins C and P in redox processes of the body, forming a single system. This is indirectly evidenced by the therapeutic effect provided by the complex of vitamin C and bioflavonoids, called ascorutin. Vitamin P and vitamin C are closely related.

Rutin increases the activity of ascorbic acid. Protecting from oxidation, helps to better assimilate it, it is rightfully considered the "main partner" of ascorbic acid. By strengthening the walls of blood vessels and reducing their fragility, it thereby reduces the risk of internal hemorrhages and prevents the formation of atherosclerotic plaques.

Normalizes high blood pressure, contributing to the expansion of blood vessels. Promotes the formation of connective tissue, and therefore the rapid healing of wounds and burns. Helps prevent varicose veins.

It has a positive effect on the functioning of the endocrine system. It is used for prevention and additional means in the treatment of arthritis - a serious disease of the joints and gout.

Increases immunity, has antiviral activity.

Diseases: Clinical manifestation hypoavitaminosis vitamin P is characterized by increased bleeding of the gums and pinpoint subcutaneous hemorrhages, general weakness, fatigue and pain in the extremities.

Hypervitaminosis: Flavonoids are not toxic and there have been no cases of overdose, the excess received with food is easily excreted from the body.

Causes: The lack of bioflavonoids can occur against the background of long-term use of antibiotics (or in high doses) and other potent drugs, with any adverse effect on the body, such as trauma or surgery.

LECTURE COURSE

FOR GENERAL BIOCHEMISTRY

Module 8. Biochemistry of water-salt metabolism and acid-base state

Yekaterinburg,

LECTURE #24

Topic: Water-salt and mineral metabolism

Faculties: medical and preventive, medical and preventive, pediatric.

Water-salt exchange - exchange of water and basic electrolytes of the body (Na +, K +, Ca 2+, Mg 2+, Cl -, HCO 3 -, H 3 PO 4).

electrolytes - substances that dissociate in solution into anions and cations. They are measured in mol/l.

Non-electrolytes- substances that do not dissociate in solution (glucose, creatinine, urea). They are measured in g / l.

Mineral exchange - the exchange of any mineral components, including those that do not affect the main parameters of the liquid medium in the body.

Water - the main component of all body fluids.

The biological role of water

Water is a universal solvent for most organic (except lipids) and inorganic compounds.

Water and substances dissolved in it create the internal environment of the body.

Water provides the transport of substances and thermal energy throughout the body.

A significant part of the chemical reactions of the body takes place in the aqueous phase.

Water is involved in the reactions of hydrolysis, hydration, dehydration.

Determines the spatial structure and properties of hydrophobic and hydrophilic molecules.

In complex with GAG, water performs a structural function.

General properties of body fluids

All body fluids are characterized by common properties: volume, osmotic pressure and pH value.

Volume. In all terrestrial animals, fluid makes up about 70% of body weight.

With complete deprivation of water, death occurs after 6-8 days, when the amount of water in the body decreases by 12%.

All body fluid is divided into intracellular (67%) and extracellular (33%) pools.

extracellular pool (extracellular space) consists of:

intravascular fluid;

Interstitial fluid (intercellular);

Transcellular fluid (fluid of the pleural, pericardial, peritoneal cavities and synovial space, cerebrospinal and intraocular fluid, secretion of sweat, salivary and lacrimal glands, secretion of the pancreas, liver, gallbladder, gastrointestinal tract and respiratory tract).

Between the pools, liquids are intensively exchanged. The movement of water from one sector to another occurs when the osmotic pressure changes.

Osmotic pressure - This is the pressure exerted by all the substances dissolved in water. The osmotic pressure of the extracellular fluid is determined mainly by the concentration of NaCl.