Department of Biochemistry
I approve
Head department prof., doctor of medical sciences
Meshchaninov V.N.
_____‘’_____________2006
LECTURE No. 25
Topic: Water-salt and mineral metabolism
Faculties: therapeutic and preventive, medical and preventive, pediatric.
Water-salt metabolism – 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 metabolism– exchange of any mineral components, including those that do not affect the basic parameters of the liquid environment in the body.
Water- the main component of all body fluids.
Biological role water
- Water is a universal solvent for most organic (except lipids) and inorganic compounds.
- Water and the substances dissolved in it create the internal environment of the body.
- Water ensures the transport of substances and thermal energy throughout the body.
- Substantial part chemical reactions organism occurs in the aqueous phase.
- Water participates in the reactions of hydrolysis, hydration, and dehydration.
- Determines the spatial structure and properties of hydrophobic and hydrophilic molecules.
- In combination with GAGs, 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.
The distribution of water in the body depends on age, gender, muscle mass, body type and amount of fat. 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, thin 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 old 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 the sweat, salivary and lacrimal glands, secretion of the pancreas, liver, gallbladder, gastrointestinal tract and respiratory tract).
Liquids are intensively exchanged between pools. The movement of water from one sector to another occurs when there is a change osmotic pressure.
Osmotic pressure – This is the pressure created by all 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 overall total concentration is osmotically active substances approximately the same.
pH– negative decimal logarithm of proton concentration. The pH value depends on the intensity of 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 the exchange, the pH value can differ markedly both within cells of different tissues and in different compartments of the same cell (in the cytosol the acidity is neutral, in lysosomes and in the intermembrane space of mitochondria it is highly acidic). In the intercellular fluid different organs In both tissues and blood plasma, the pH value, like osmotic pressure, is a relatively constant value.
REGULATION OF 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.
Organs regulating water-salt metabolism
The entry of water and salts into the body occurs through the gastrointestinal tract; this process is controlled by the feeling of thirst and salt appetite. The kidneys remove excess water and salts from the body. In addition, water is removed from the body by the skin, lungs and gastrointestinal tract.
Body water balance
For the gastrointestinal tract, skin and lungs, the excretion of water is a side process that occurs as a result of their performance of their main functions. For example, the gastrointestinal tract loses water when undigested substances, metabolic products and xenobiotics are released from the body. The lungs lose water during breathing, and the skin during thermoregulation.
Changes in the functioning of the kidneys, skin, lungs and gastrointestinal tract can lead to disruption of water-salt homeostasis. For example, in hot climates, 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 regulating water-salt metabolism
Vasopressin
Antidiuretic hormone (ADH), or vasopressin- a peptide with a molecular weight of about 1100 D, containing 9 AA connected by one disulfide bridge.
ADH is synthesized in the neurons of the hypothalamus and transported to the nerve endings of the posterior lobe of the pituitary gland (neurohypophysis).
High osmotic pressure of the extracellular fluid activates osmoreceptors in 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, stimulating the expression of the membrane protein gene - aquaporina-2 . Aquaporin-2 is integrated into the apical membrane of cells, forming water channels in it. Through these channels, water is reabsorbed from urine into the interstitial space by passive diffusion and the urine is concentrated.
In the absence of ADH, urine does not concentrate (density<1010г/л) и может выделяться в очень больших количествах (>20 l/day), which leads to dehydration of the body. This condition is called diabetes insipidus .
The causes of ADH deficiency and diabetes insipidus are: genetic defects in the synthesis of prepro-ADG in the hypothalamus, defects in the processing and transport of proADG, damage to the hypothalamus or neurohypophysis (for example, as a result of traumatic brain injury, tumor, ischemia). Nephrogenic diabetes insipidus occurs due to a mutation in the ADH type V 2 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 vascular SMCs. The vasoconstrictor effect of ADH occurs at high concentrations of ADH.
Concentration calcium in the extracellular fluid is normally maintained at a strictly constant level, rarely increasing or decreasing by a few 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 due to the essential role of calcium in many physiological processes, including the contraction of skeletal, cardiac and smooth muscles, blood clotting, and the transmission of nerve impulses. Excitable tissues, including nervous tissue, are very sensitive to changes in calcium concentration, and an increase in the concentration of calcium ions compared to normal (hypscalcemia) causes increasing damage nervous system; on the contrary, a decrease in calcium concentration (hypocalcemia) increases the excitability of the nervous system.
An important feature of the regulation of extracellular calcium concentration: only about 0.1% of the total amount of calcium in the body is present in the extracellular fluid, about 1% is located inside the cells, and the rest is stored in the bones, so bones can be considered as a large storehouse of calcium, releasing it in extracellular space, if the calcium concentration there decreases, and, on the contrary, taking excess calcium for storage.
Approximately 85% phosphates The body is stored in bones, 14 to 15% is stored in cells, and only less than 1% is present in extracellular fluid. Phosphate concentrations in the extracellular fluid are not as tightly regulated as calcium concentrations, although they perform a variety of important functions in jointly controlling many processes with calcium.
Absorption of calcium and phosphates in the intestine and their excretion in feces. The usual rate of calcium and phosphate intake is approximately 1000 mg/day, which corresponds to the amount extracted from 1 liter of milk. Typically, divalent cations, such as ionized calcium, are poorly absorbed in the intestine. However, as discussed below, vitamin D promotes intestinal absorption of calcium, and nearly 35% (about 350 mg/day) of calcium intake is absorbed. The calcium remaining in the intestines 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 exfoliated cells. Thus, about 90% (900 mg/day) of the daily calcium intake is excreted in the feces.
Hypocalcemia causes stimulation 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 results in increased permeability to sodium ions, facilitating action potential generation. If the concentration of calcium ions drops to a level of 50% of normal, 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 body fluids 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, decreased appetite and constipation, possibly due to a decrease in contractile activity of the muscular wall of the gastrointestinal tract.
These depressive effects begin to appear when calcium levels rise above 12 mg/dL and become noticeable when calcium levels exceed 15 mg/dL.
The resulting nerve impulses reach the skeletal muscles, causing tetanic contractions. Therefore, hypocalcemia causes tetany, and 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 phosphates that are excreted in the feces in the form of calcium salts, almost all phosphates contained in the daily diet are absorbed from the intestines 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 protein bound and therefore not filtered from the glomerular capillaries. The remaining amount combines with anions, such as phosphates (9%), or is ionized (50%) and filtered by the glomerulus into the renal tubules.
Normally, 99% of filtered calcium is reabsorbed in the kidney tubules, 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 tubules, loop of Henle and at the beginning of the distal tubules. The remaining 10% of calcium is then reabsorbed at the end of the distal tubules and 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 is slightly higher than 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 the abundant flow mechanism. This means that when the concentration of phosphate in plasma decreases 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 phosphates exceeds the norm, its loss in the urine is directly proportional to the additional increase in its concentration. The kidneys regulate the concentration of phosphates in the extracellular space by changing the rate of phosphate excretion according to their plasma concentration and the rate of phosphate filtration in the kidney.
However, as we will see later, parathyroid hormone can significantly increase renal excretion of phosphate, so it plays an important role in regulating plasma phosphate concentrations along with controlling calcium concentrations. Parathyroid hormone is a powerful regulator of calcium and phosphate concentrations, exerting its influence by controlling reabsorption processes in the intestines, excretion in the kidney and the exchange of these ions between extracellular fluid and bone.
Excessive activity of the parathyroid glands causes rapid leaching of calcium salts from the bones with the subsequent 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 thyroid gland, in pairs at its upper and lower poles. Each parathyroid gland is a structure 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 surgery on the thyroid gland, because they often look like an additional lobe of the thyroid gland. That is why, until 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 disturbances; removal of three or all four glands leads to transient hypoparathyroidism. But even a small amount of remaining parathyroid tissue can, due to hyperplasia, ensure normal function of the parathyroid glands.
The adult parathyroid glands consist predominantly of chief cells and more or less oxyphilic cells, which are absent in many animals and in young people. Chief cells presumably secrete most, if not all, of parathyroid hormone, and oxyphilic cells have their own purpose.
They are believed to be a modification or exhausted form of the main cells that no longer synthesize the hormone.
Chemical structure of parathyroid hormone. PTH is isolated in purified form. Initially, it is synthesized on ribosomes in the form of a preprohormone, a polypeptide chain of amino acid residues. Then it is cleaved to the prohormone, consisting of 90 amino acid residues, then to the hormone stage, which includes 84 amino acid residues. This process is carried out in the endoplasmic reticulum and 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 eliminate the form of the hormone, consisting of 84 amino acid residues, very quickly, within a few minutes, while the remaining numerous fragments ensure the maintenance of a high degree of hormonal activity for a long time.
Thyroid calcitonin- a hormone produced in mammals and 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 one), but in the ultimobranchial corpuscles and is therefore simply called calcitonin. Thyroid calcitonin takes part in the regulation of phosphorus-calcium metabolism in the body, as well as the balance of activity of osteoclasts and osteoblasts, and is a functional antagonist of parathyroid hormone. Thyroid calcitonin 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. Thyroid calcitonin is a protein-peptide hormone with a molecular weight of 3600. Strengthens the deposition of phosphorus-calcium salts on the collagen matrix of bones. Thyroid calcitonin, like parathyroid hormone, increases phosphaturia.
Calcitriol
Structure: It is a derivative of vitamin D and is classified as a steroid.
Synthesis: Cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) formed in the skin under the influence 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 of 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 intestines 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 bone tissue enhances calcium resorption. Pathology: Hypofunction Corresponds to the picture of hypovitaminosis D. Role 1.25-dihydroxycalciferol in the exchange of Ca and P.: Enhances the absorption of Ca and P from the intestine, Enhances the reabsorption of Ca and P by the kidneys, Enhances the mineralization of young bone, Stimulates osteoclasts and the release of Ca from old bone.
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 during ultraviolet irradiation from 7-dehydrocholesterol in an amount of 0.5-1.0 mcg/day.
Daily requirement: For children - 12-25 mcg or 500-1000 IU; for adults the need is much less.
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tripling: The vitamin is presented in two forms - ergocalciferol and cholecalciferol. Chemically, ergocalciferol differs from cholecalciferol by the presence in the molecule of a double bond between C22 and C23 and a methyl group at C24.
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, at C1. 1,25-dihydroxycholecalciferol or calcitriol is formed. The hydroxylation reaction in the kidneys is stimulated by parathyroid hormone, prolactin, growth hormone and is suppressed by high concentrations of phosphates and calcium.
Biochemical functions: 1. An increase in the concentration of calcium and phosphates 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+ ions 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 bone tissue, as it promotes the differentiation of monocytes and macrophages into osteoclasts and reduces 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 their production of nitrogen-containing free radicals, 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 the reabsorption of calcium in the kidneys.
Hypovitaminosis. Acquired hypovitaminosis. Reason.
It often occurs with nutritional deficiency in children, with insufficient insolation in people who do not go outside, or with national peculiarities of clothing. Hypovitaminosis can also be caused by a decrease in the hydroxylation of calciferol (liver and kidney diseases) 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 being supplied with food, calcium is not absorbed in the intestines and is lost in the kidneys. This leads to a decrease in the concentration of calcium in the blood plasma, impaired mineralization of bone tissue and, as a consequence, 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, rachitic rosary on the ribs, enlargement of the abdomen due to hypotonia of the muscles, delayed teething and overgrowth of the fontanelles.
In adults, osteomalacia is also observed, i.e. Osteoid continues to be synthesized, but is not mineralized. The development of osteoporosis is also partly associated with vitamin D deficiency.
Hereditary hypovitaminosis
Vitamin D-dependent hereditary rickets type I, in which there is a recessive defect in renal α1-hydroxylase. Manifested by developmental delay, rachitic skeletal features, etc. Treatment is calcitriol preparations or large doses of vitamin D.
Vitamin D-dependent hereditary rickets type II, in which there is a defect in tissue calcitriol receptors. Clinically, the disease is similar to type I, but additionally alopecia, milia, epidermal cysts, and muscle weakness are noted. Treatment varies depending on the severity of the disease, but large doses of calciferol help.
Hypervitaminosis. Cause
Excessive consumption with drugs (at least 1.5 million IU per day).
Clinical picture: Early signs of vitamin D overdose include nausea, headache, loss of appetite and body weight, polyuria, thirst and polydipsia. There may be constipation, hypertension, and muscle stiffness. Chronic excess of vitamin D leads to hypervitaminosis, which is characterized by: demineralization of bones, leading to their fragility and fractures. increase in the concentration of calcium and phosphorus ions in the blood, leading to calcification of blood vessels, lung and kidney tissue.
Dosage forms
Vitamin D – fish fat, ergocalciferol, cholecalciferol.
1,25-Dioxycalciferol (active form) – osteotriol, oxidevit, rocaltrol, forcal plus.
58. Hormones, derivatives of fatty acids. Synthesis. Functions.
According to their chemical nature, hormonal molecules belong to three groups of compounds:
1) proteins and peptides; 2) derivatives of amino acids; 3) steroids and fatty acid derivatives.
Eicosanoids (είκοσι, Greek - twenty) include oxidized derivatives of eicosan acids: eicosotriene (C20:3), arachidonic acid (C20:4), timnodonic acid (C20:5). The activity of eicosanoids varies significantly depending on the number of double bonds in the molecule, which depends on the structure of the original compound. Eicosanoids are called hormone-like substances because. they can only have a local effect, remaining in the blood for several seconds. Found in all organs and tissues with almost all types of cells. Eicosanoids cannot be deposited; they are destroyed within a few seconds, and therefore cells must constantly synthesize them from incoming ω6- and ω3-series fatty acids. There are three main groups:
Prostaglandins (Pg)– synthesized in almost all cells, except erythrocytes and lymphocytes. There are types of prostaglandins A, B, C, D, E, F. The functions of prostaglandins are reduced to changes in the tone of smooth muscles of the bronchi, genitourinary and vascular systems, and gastrointestinal tract, while the direction of changes varies depending on the type of prostaglandins, cell type and conditions . They also affect body temperature. Can activate adenylate cyclase Prostacyclins are a subtype of prostaglandins (Pg I), cause dilatation of small vessels, but also have a special function - they inhibit platelet aggregation. Their activity increases with increasing number of double bonds. They are synthesized in the endothelium of myocardial vessels, uterus, and gastric mucosa. Thromboxanes (Tx) are formed in platelets, stimulate their aggregation and cause vasoconstriction. Their activity decreases with increasing 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 motility, chemotaxis and migration of cells to the site of inflammation; in general, they activate inflammatory reactions, preventing its chronicity. They also cause contraction of the bronchial muscles (in doses 100-1000 times less than histamine). increase membrane permeability for Ca2+ ions. Since cAMP and Ca 2+ ions stimulate the synthesis of eicosanoids, a positive feedback loop is closed in the synthesis of these specific regulators.
AND 
source free eicosanoic acids are phospholipids cell membrane. Under the influence of specific and nonspecific stimuli, phospholipase A 2 or a combination of phospholipase C and DAG lipase are activated, which cleave fatty acid from the C2 position of phospholipids.
P 
Olinesaturated acid metabolizes mainly in 2 ways: cyclooxygenase and lipoxygenase, the activity of which in different cells is expressed in varying degrees. The cyclooxygenase pathway is responsible for the synthesis of prostaglandins and thromboxanes, the lipoxygenase pathway is responsible for the synthesis of leukotrienes.
Biosynthesis Most eicosanoids begin with the cleavage of arachidonic acid from membrane phospholipid or diacyl-glycerol in the plasma membrane. The synthetase complex is a multienzyme system that functions primarily on ER membranes. These eicosanoids easily penetrate through the plasma membrane of cells, and then through the intercellular space they are transferred to neighboring cells or released into the blood and lymph. The rate of eicosanoid synthesis has increased under the influence of hormones and neurotransmitters that act on adenylate cyclase or increase the concentration of Ca 2+ ions in cells. The most intensive formation of prostaglandins occurs in the testes and ovaries. In many tissues, cortisol inhibits the absorption of arachidonic acid, which leads to the suppression of eicosanoid production, and thereby has an anti-inflammatory effect. Prostaglandin E1 is a powerful pyrogen. 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 are found 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 acid 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.
Vitamins of group E (tocopherols). The name “tocopherol” of vitamin E comes from the Greek “tokos” - “birth” and “ferro” - to wear. It was found in oil from sprouted wheat grains. There is currently a known family of tocopherols and tocotrienols found in natural sources. All of them are metal derivatives of the original compound tocol, are very similar in structure and are designated by letters of the Greek alphabet. α-tocopherol exhibits the greatest biological activity.
Tocopherol is insoluble in water; like vitamins A and D, it is fat soluble and resistant to acids, alkalis and high temperatures. Regular boiling has almost no effect on it. But light, oxygen, ultraviolet rays or chemical oxidizing agents are destructive.
IN 
itamin E is contained in chap. arr. in lipoprotein membranes of cells and subcellular organelles, where it is localized due to intermol. interaction with unsaturated fatty ones. His biol. activity based on the ability to form stable freedom. radicals as a result of the abstraction of the H atom from the hydroxyl group. These radicals can interact. from free radicals involved in the formation of org. peroxides. Thus, vitamin E prevents the oxidation of unsaturation. lipids and protects against biol destruction. membranes and other molecules such as DNA.
Tocopherol increases the biological activity of vitamin A by protecting the unsaturated side chain from oxidation.
Sources: for a person - vegetable oils, lettuce, cabbage, cereal seeds, butter, egg yolk.
Daily requirement for an adult, the vitamin contains approximately 5 mg.
Clinical manifestations of deficiency in humans have not been fully studied. The positive effect of vitamin E is known in the treatment of impaired fertilization, repeated involuntary abortions, and some forms of muscle weakness and dystrophy. The use of vitamin E is indicated for premature babies and children who are bottle-fed, 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 red blood cell membranes as a result of lipid peroxidation.
U 
Biquinones (coenzymes Q)– a widely distributed substance and has been found in plants, fungi, animals and m/o. They belong to the group of fat-soluble vitamin-like compounds, are poorly soluble in water, but are destroyed when exposed to oxygen and high temperatures. In the classical sense, ubiquinone is not a vitamin, since it is synthesized in sufficient quantities in the body. But in some diseases, the natural synthesis of coenzyme Q decreases and there is not enough of it to meet the need, then it becomes an indispensable factor.
U 
Biquinones play an important role in the cell bioenergetics of most prokaryotes and all eukaryotes. Basic function of ubiquinones - transfer of electrons and protons from decomposition. 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. group of proteins. Three classes of Q-binding proteins acting in respiration have been identified. chains at the sites of functioning of the enzymes succinate-biquinone reductase, NADH-ubiquinone reductase and cytochromes b and c 1.
During the process of electron transfer from NADH dehydrogenase through FeS to ubiquinone, it is reversibly converted to hydroquinone. Ubiquinone performs a collector function, 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) anemia2) changes in skeletal muscles 3) heart failure 4) changes in bone marrow
Overdose symptoms: is 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, kidneys, beef, pork, fish, eggs, chicken. Synthesized by intestinal microflora.
WITH 
specific requirement: It is believed that under normal conditions the body covers the requirement 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 protons are lost by the substrate.
63. Vitamins C and P, structure, role. Scurvy.
Vitamin P(bioflavonoids; rutin, citrine; permeability vitamin)
It is currently known that the concept of “vitamin P” unites 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 capillary resistance (from the 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 temperature easily destroys it.
AND 
sources: lemons, buckwheat, chokeberry, black currant, tea leaves, rose hips.
Daily requirement for humans 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 members of the vitamin P group have a hypotensive effect.
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Vitamin P “protects” hyaluronic acid, which strengthens the walls of blood vessels and is the main component of the biological lubrication of joints, from the destructive action of hyaluronidase enzymes. Bioflavonoids stabilize the basic substance of 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 against oxidation and helping its better absorption, it is rightfully considered the “main partner” of ascorbic acid. Strengthening the walls blood vessels and by reducing their fragility, it thereby reduces the risk of internal hemorrhages and prevents the formation of atherosclerotic plaques.
Normalizes high blood pressure, promoting vasodilation. Promotes the formation of connective tissue, and therefore the rapid healing of wounds and burns. Helps prevent varicose veins.
Positively affects the functioning of the endocrine system. Used for prevention and as an additional remedy in the treatment of arthritis - a severe disease of the joints and gout.
Increases immunity and has antiviral activity.
Diseases: Clinical manifestation hypovitaminosis Vitamin P deficiency is characterized by increased bleeding of the gums and pinpoint subcutaneous hemorrhages, general weakness, fatigue and pain in the extremities.
Hypervitaminosis: Flavonoids are non-toxic and no cases of overdose have been observed; excess intake from food is easily eliminated from the body.
Causes: A lack of bioflavonoids can occur during prolonged use of antibiotics (or in large doses) and other potent drugs, with any adverse effect on the body, such as injury or surgery.
FUNCTIONAL BIOCHEMISTRY
(Water-salt metabolism. Biochemistry of kidneys and urine)
TUTORIAL
Reviewer: Professor N.V. Kozachenko
Approved at the meeting of the department, pr. No. _____ dated _______________2004.
Approved by the manager department _____________________________________________
Approved by the MK of the medical-biological and pharmaceutical faculties
Project No. _____ dated _______________2004
Chairman________________________________________________
Water-salt metabolism
One of the most frequently disrupted types of metabolism in pathology is water-salt metabolism. It is associated with the constant movement of water and minerals from the external environment of the body to the internal, and vice versa.
In the adult human body, water accounts for 2/3 (58-67%) of body weight. About half of its volume is concentrated in the muscles. The need for water (a person receives up to 2.5-3 liters of liquid daily) is covered by its intake in the form of drinking (700-1700 ml), preformed water included in food (800-1000 ml), and water formed in in the body during metabolism - 200-300 ml (with the combustion of 100 g of fats, proteins and carbohydrates, 107.41 and 55 g of water are formed, respectively). Endogenous water in relatively large quantities is synthesized upon activation of the process of fat oxidation, which is observed under various, especially prolonged stress conditions, stimulation of the sympathetic-adrenal system, unloading diet therapy (often used to treat obese patients).
Due to the constantly occurring obligatory water losses, the internal volume of fluid in the body remains unchanged. Such losses include renal (1.5 l) and extrarenal, associated with the release of fluid through the gastrointestinal tract (50-300 ml), Airways and skin (850-1200 ml). In general, the volume of mandatory water losses is 2.5-3 liters, largely depending on the amount of toxins removed from the body.
The participation of water in life processes is very diverse. Water is a solvent for many compounds, a direct component of a number of physicochemical and biochemical transformations, and a transporter of endo- and exogenous substances. In addition, it performs a mechanical function, weakening the friction of ligaments, muscles, and the surface of the cartilage of joints (thereby facilitating their mobility), and participates in thermoregulation. Water maintains homeostasis, depending on the osmotic pressure of the plasma (isosmia) and the volume of fluid (isovolemia), the functioning of the mechanisms regulating the acid-base state, and the occurrence of processes that ensure constant temperature (isothermia).
In the human body, water exists in three main physicochemical states, according to which they distinguish: 1) free, or mobile, water (it makes up the bulk of the intracellular fluid, as well as blood, lymph, interstitial fluid); 2) water, bound by hydrophilic colloids, and 3) constitutional, included in the structure of the molecules of proteins, fats and carbohydrates.
In the body of an adult weighing 70 kg, the volume of free water and water bound by hydrophilic colloids is approximately 60% of body weight, i.e. 42 l. This fluid is represented by intracellular water (accounting for 28 liters, or 40% of body weight), which makes up intracellular sector, and extracellular water (14 l, or 20% of body weight), forming extracellular sector. The latter contains intravascular (intravascular) fluid. This intravascular sector is formed by plasma (2.8 l), which accounts for 4-5% of body weight, and lymph.
Interstitial water includes intercellular water itself (free intercellular fluid) and organized extracellular fluid (constituting 15-16% of body weight, or 10.5 l), i.e. water of ligaments, tendons, fascia, cartilage, etc. In addition, the extracellular sector includes water located in some cavities (abdominal and pleural cavity, pericardium, joints, ventricles of the brain, chambers of the eye, etc.), as well as in gastrointestinal tract. The fluid of these cavities does not actively participate in metabolic processes.
The water of the human body does not stagnate in its various sections, but constantly moves, continuously exchanging with other sectors of the liquid and with the external environment. The movement of water is largely due to the secretion of digestive juices. So, with saliva and pancreatic juice, about 8 liters of water per day are sent into the intestinal tube, but this water is practically not lost due to absorption in lower parts of the digestive tract.
Vital elements are divided into macronutrients(daily requirement >100 mg) and microelements(daily requirement<100 мг). К макроэлементам относятся натрий (Na), калий (К), кальций (Ca), магний (Мg), хлор (Cl), фосфор (Р), сера (S) и иод (I). К жизненно важным микроэлементам, необходимым лишь в следовых количествах, относятся железо (Fe), цинк (Zn), марганец (Μn), медь (Cu), кобальт (Со), хром (Сr), селен (Se) и молибден (Мо). Фтор (F) не принадлежит к этой группе, однако он необходим для поддержания в здоровом состоянии костной и зубной ткани. Вопрос относительно принадлежности к жизненно важным микроэлементам ванадия, никеля, олова, бора и кремния остается открытым. Такие элементы принято называть условно эссенциальными.
Table 1 (column 2) shows the average content minerals in the body of an adult (based on a weight of 65 kg). Average daily An adult's need for these elements is given in column 4. In children and women during pregnancy and breastfeeding, as well as in patients, the need for microelements is usually higher.
Since many elements can be stored in the body, deviations from the daily norm are compensated over time. Calcium in the form of apatite is stored in bone tissue, iodine is stored in thyroglobulin in the thyroid gland, iron is stored in ferritin and hemosiderin in the bone marrow, spleen and liver. The liver is the storage site for many microelements.
Mineral metabolism is controlled by hormones. This applies, for example, to the consumption of H 2 O, Ca 2+, PO 4 3-, the binding of Fe 2+, I -, the excretion of H 2 O, Na +, Ca 2+, PO 4 3-.
The amount of minerals absorbed from food usually depends on the metabolic needs of the body and, in some cases, on the composition of the food. As an example of the influence of food composition, consider calcium. The absorption of Ca 2+ ions is promoted by lactic and citric acids, while phosphate ion, oxalate ion and phytic acid inhibit calcium absorption due to complexation and the formation of poorly soluble salts (phytin).
Mineral deficiency- the phenomenon is not so rare: it occurs for various reasons, for example, due to a monotonous diet, impaired digestibility, and various diseases. Calcium deficiency can occur during pregnancy, as well as with rickets or osteoporosis. Chlorine deficiency occurs due to a large loss of Cl ions - with severe vomiting.
Due to insufficient iodine content in food products, iodine deficiency and goiter have become common in many areas of Central Europe. Magnesium deficiency can occur due to diarrhea or due to a monotonous diet due to alcoholism. A lack of microelements in the body often manifests itself as a disorder of hematopoiesis, i.e. anemia.
The last column lists the functions performed in the body by these minerals. From the table data it is clear that almost all macronutrients function in the body as structural components and electrolytes. Signaling functions are performed by iodine (in the composition of iodothyronine) and calcium. Most microelements are cofactors of proteins, mainly enzymes. Quantitatively, the body is dominated by iron-containing proteins hemoglobin, myoglobin and cytochrome, as well as more than 300 zinc-containing proteins.
Table 1
Related information.
Regulation of water metabolism is carried out neurohumorally, in particular, by various parts of the central nervous system: the cerebral cortex, diencephalon and medulla oblongata, sympathetic and parasympathetic ganglia. Many endocrine glands are also involved. The effect of hormones in this case is that they change the permeability of cell membranes to water, ensuring its release or readsorption. The body's need for water is regulated by the feeling of thirst. Already at the first signs of blood thickening, thirst arises as a result of reflex excitation of certain areas of the cerebral cortex. The water consumed is absorbed through the intestinal wall, and its excess does not cause blood thinning . From blood, it quickly passes into the intercellular spaces of loose connective tissue, liver, skin, etc. These tissues serve as a depot of water in the body. Individual cations have a certain influence on the flow and release of water from tissues. Na + ions promote the binding of proteins by colloidal particles, K + and Ca 2+ ions stimulate the release of water from the body.
Thus, vasopressin of the neurohypophysis (antidiuretic hormone) promotes the readsorption of water from primary urine, reducing the excretion of the latter from the body. Hormones of the adrenal cortex - aldosterone, deoxycorticosterol - contribute to sodium retention in the body, and since sodium cations increase tissue hydration, water is also retained in them. Other hormones stimulate the secretion of water by the kidneys: thyroxine - a hormone of the thyroid gland, parathyroid hormone - a hormone of the parathyroid gland, androgens and estrogens - hormones of the sex glands. Thyroid hormones stimulate the secretion of water through the sweat glands. The amount of water in the tissues, primarily free water, increases with disease kidneys, impaired function of the cardiovascular system, protein starvation, impaired liver function (cirrhosis). An increase in water content in the intercellular spaces leads to edema. Insufficient formation of vasopressin leads to increased diuresis and diabetes insipidus. Dehydration of the body is also observed with insufficient production of aldosterone in the adrenal cortex.
Water and substances dissolved in it, including mineral salts, create the internal environment of the body, the properties of which remain constant or change in a natural way when the functional state of organs and cells changes. The main parameters of the liquid environment of the body are osmotic pressure,pH And volume.
The osmotic pressure of the extracellular fluid largely depends on the salt (NaCl), which is contained in the highest concentration in this fluid. Therefore, the main mechanism for regulating osmotic pressure is associated with a change in the rate of release of either water or NaCl, as a result of which the concentration of NaCl in tissue fluids changes, and therefore the osmotic pressure also changes. Volume regulation occurs by simultaneously changing the rate of release of both water and NaCl. In addition, the thirst mechanism regulates water consumption. pH regulation is ensured by the selective release of acids or alkalis in the urine; Depending on this, the pH of urine can vary from 4.6 to 8.0. Disturbances in water-salt homeostasis are associated with pathological conditions such as tissue dehydration or edema, increased or decreased blood pressure, shock, acidosis, and alkalosis.
Regulation of osmotic pressure and extracellular fluid volume. The excretion of water and NaCl by the kidneys is regulated by antidiuretic hormone and aldosterone.
Antidiuretic hormone (vasopressin). Vasopressin is synthesized in neurons of the hypothalamus. Osmoreceptors of the hypothalamus, when the osmotic pressure of tissue fluid increases, stimulate the release of vasopressin from secretory granules. Vasopressin increases the rate of water reabsorption from primary urine and thereby reduces diuresis. The urine becomes more concentrated. In this way, the antidiuretic hormone maintains the required volume of fluid in the body without affecting the amount of NaCl released. The osmotic pressure of the extracellular fluid decreases, i.e., the stimulus that caused the release of vasopressin is eliminated. In some diseases that damage the hypothalamus or pituitary gland (tumors, injuries, infections), the synthesis and secretion of vasopressin decreases and develops diabetes insipidus.
In addition to reducing diuresis, vasopressin also causes a constriction of arterioles and capillaries (hence the name), and, consequently, an increase in blood pressure.
Aldosterone. This steroid hormone is produced in the adrenal cortex. Secretion increases as NaCl concentration in the blood decreases. In the kidneys, aldosterone increases the rate of reabsorption of Na + (and with it C1) in the nephron tubules, which causes NaCl retention in the body. This removes the stimulus that caused the secretion of aldosterone. Excessive secretion of aldosterone leads, accordingly, to excessive NaCl retention and an increase in the osmotic pressure of the extracellular fluid. And this serves as a signal for the release of vasopressin, which accelerates the reabsorption of water in the kidneys. As a result, both NaCl and water accumulate in the body; the volume of extracellular fluid increases while maintaining normal osmotic pressure.
Renin-angiotensin system. This system serves as the main mechanism for regulating aldosterone secretion; The secretion of vasopressin also depends on it. Renin is a proteolytic enzyme synthesized in juxtaglomerular cells surrounding the afferent arteriole of the renal glomerulus.
The renin-angiotensin system plays an important role in restoring blood volume, which can decrease as a result of bleeding, excessive vomiting, diarrhea, and sweating. Vasoconstriction by angiotensin II acts as an emergency measure to maintain blood pressure. Then the water and NaCl that come with drinking and food are retained in the body to a greater extent than normal, which ensures the restoration of blood volume and pressure. After this, renin ceases to be released, the regulatory substances already present in the blood are destroyed and the system returns to its original state.
A significant decrease in the volume of circulating fluid can cause a dangerous disruption of the blood supply to tissues before the regulatory systems restore blood pressure and volume. In this case, the functions of all organs, and, above all, the brain, are disrupted; a condition called shock occurs. In the development of shock (as well as edema), a significant role is played by changes in the normal distribution of fluid and albumin between the bloodstream and the intercellular space. Vasopressin and aldosterone are involved in the regulation of water-salt balance, acting at the level of the nephron tubules - they change the rate of reabsorption of components of primary urine.
Water-salt metabolism and secretion of digestive juices. The volume of daily secretion of all digestive glands is quite large. Under normal conditions, the water from these fluids is reabsorbed in the intestines; profuse vomiting and diarrhea can cause a significant decrease in extracellular fluid volume and tissue dehydration. A significant loss of fluid with digestive juices entails an increase in the concentration of albumin in the blood plasma and intercellular fluid, since albumin is not excreted with secretions; for this reason, the osmotic pressure of the intercellular fluid increases, water from the cells begins to pass into the intercellular fluid and cell functions are disrupted. High osmotic pressure of extracellular fluid also leads to a decrease or even cessation of urine formation , and if water and salts are not supplied from outside, the animal develops a coma.
