Water-salt exchange. Lectures: biochemistry of water-salt metabolism Urine is normally completely transparent. Turbidity can be caused by the presence of protein, cellular elements, bacteria, mucus, sediment in the urine

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 molecular weight 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.

WITH
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+ ions and phosphate ions in 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 of the 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 is expressed to varying degrees in different cells. 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 infants and bottle-fed children, since cow's milk 10 times less vitamin E than women's. 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.

-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 main substance 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 the 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.

LECTURE COURSE
IN GENERAL BIOCHEMISTRY

Module 8. Biochemistry of water-salt metabolism.

Ekaterinburg,
2009

Topic: Water-salt and mineral metabolism

Water-salt metabolism is the exchange of water and the body’s main electrolytes (Na +, K +, Ca 2+, Mg 2+, Cl -, HCO 3 -, H 3 PO 4).
Electrolytes are substances that dissociate in solution into anions and cations. They are measured in mol/l.
Nonelectrolytes are substances that do not dissociate in solution (glucose, creatinine, urea). They are measured in g/l.
Biological role of 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.

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

2. Hormones that regulate water-salt metabolism
Vasopressin
Antidiuretic hormone (ADH), or vasopressin, is 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 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 through 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 of which proteins are phosphorylated, stimulating the expression of the membrane protein gene - aquaporin-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.
Natriuretic hormone (atrial natriuretic factor, ANF, atriopeptin)
PNP is a peptide containing 28 AA with 1 disulfide bridge, synthesized mainly in atrial cardiomyocytes.
The secretion of PNP is stimulated mainly by an increase in blood pressure, as well as an increase in plasma osmotic pressure, heart rate, and the concentration of catecholamines and glucocorticoids in the blood.
PNP acts through the guanylate cyclase system, activating protein kinase G.
In the kidneys, PNF dilates afferent arterioles, which increases renal blood flow, filtration rate, and Na + excretion.
In peripheral arteries, PNF reduces smooth muscle tone, which dilates arterioles and lowers blood pressure. In addition, PNF inhibits the release of renin, aldosterone and ADH.
Renin-angiotensin-aldosterone system
Renin
Renin is a proteolytic enzyme produced by juxtaglomerular cells located along the afferent (afferent) arterioles of the renal corpuscle. Renin secretion is stimulated by a drop in pressure in the afferent arterioles of the glomerulus, caused by a decrease in blood pressure and a decrease in Na + concentration. Renin secretion is also facilitated by a decrease in impulses from the baroreceptors of the atria and arteries as a result of a decrease in blood pressure. Renin secretion is inhibited by Angiotensin II, high blood pressure.
In the blood, renin acts on angiotensinogen.
Angiotensinogen - ? 2-globulin, from 400 AK. The formation of angiotensinogen occurs in the liver and is stimulated by glucocorticoids and estrogens. Renin hydrolyzes the peptide bond in the angiotensinogen molecule, cleaving from it the N-terminal decapeptide - angiotensin I, which has no biological activity.
Under the action of the antiotensin-converting enzyme (ACE) (carboxydipeptidyl peptidase) of edothelial cells, lungs and blood plasma, 2 AA are removed from the C-terminus of angiotensin I and angiotensin II (octapeptide) is formed.
Angiotensin II
Angiotensin II functions through the inositol triphosphate system of cells of the zona glomerulosa of the adrenal cortex and SMCs. Angiotensin II stimulates the synthesis and secretion of aldosterone by cells of the zona glomerulosa of the adrenal cortex. High concentrations of angiotensin II cause severe vasoconstriction of peripheral arteries and increase blood pressure. In addition, angiotensin II stimulates the thirst center in the hypothalamus and inhibits the secretion of renin in the kidneys.
Angiotensin II is hydrolyzed by aminopeptidases into angiotensin III (a heptapeptide with the activity of angiotensin II, but having a 4-fold lower concentration), which is then hydrolyzed by angiotensinase (protease) to AK.
Aldosterone
Aldosterone is an active mineralocorticosteroid synthesized by cells of the zona glomerulosa of the adrenal cortex.
The synthesis and secretion of aldosterone is stimulated by angiotensin II, low concentrations of Na + and high concentrations of K + in the blood plasma, ACTH, and prostaglandins. Aldosterone secretion is inhibited by low concentrations of K +.
Aldosterone receptors are localized both in the nucleus and in the cytosol of the cell. Aldosterone induces the synthesis of: a) Na + transport proteins, which transport Na + from the lumen of the tubule to the epithelial cell of the renal tubule; b) Na + , K + -ATPases c) K + transport proteins that transfer K + from renal tubule cells into primary urine; d) mitochondrial enzymes of the TCA cycle, in particular citrate synthase, which stimulate the formation of ATP molecules necessary for active ion transport.
As a result, aldosterone stimulates Na + reabsorption in the kidneys, which causes NaCl retention in the body and increases osmotic pressure.
Aldosterone stimulates the secretion of K +, NH 4 + in the kidneys, sweat glands, intestinal mucosa and salivary glands.

The role of the RAAS system in the development of hypertension
Overproduction of RAAS hormones causes an increase in the volume of circulating fluid, osmotic and blood pressure, and leads to the development of hypertension.
An increase in renin occurs, for example, with atherosclerosis of the renal arteries, which occurs in the elderly.
Hypersecretion of aldosterone – hyperaldosteronism – occurs as a result of several reasons.
The cause of primary hyperaldosteronism (Conn's syndrome) in approximately 80% of patients is an adrenal adenoma, in other cases it is diffuse hypertrophy of cells of the zona glomerulosa that produce aldosterone.
In primary hyperaldosteronism, excess aldosterone increases Na + reabsorption in the renal tubules, which stimulates ADH secretion and water retention by the kidneys. In addition, the excretion of K +, Mg 2+ and H + ions is enhanced.
As a result, the following develop: 1). hypernatremia, causing hypertension, hypervolemia and edema; 2). hypokalemia leading to muscle weakness; 3). magnesium deficiency and 4). mild metabolic alkalosis.
Secondary hyperaldosteronism is much more common than primary hyperaldosteronism. It may be associated with heart failure, chronic kidney disease, and renin-secreting tumors. Patients are observed increased level renin, angiotensin II and aldosterone. Clinical symptoms are less pronounced than with primary aldosteronism.

CALCIUM, MAGNESIUM, PHOSPHORUS METABOLISM
Functions of calcium in the body:

Intracellular mediator of a number of hormones (inositol triphosphate system);
Participates in the generation of action potentials in nerves and muscles;
Participates in blood clotting;
Triggers muscle contraction, phagocytosis, secretion of hormones, neurotransmitters, etc.;
Participates in mitosis, apoptosis and necrobiosis;
Increases the permeability of the cell membrane for potassium ions, affects the sodium conductivity of cells, the operation of ion pumps;
Coenzyme of some enzymes;

It is a coenzyme of many enzymes (transketolase (PFSH), glucose-6ph dehydrogenase, 6-phosphogluconate dehydrogenase, gluconolactone hydrolase, adenylate cyclase, etc.);
An inorganic component of bones and teeth.

Inorganic component of bones and teeth (hydroxyapatite);
Part of lipids (phospholipids, sphingolipids);
Part of nucleotides (DNA, RNA, ATP, GTP, FMN, NAD, NADP, etc.);
Provides energy metabolism because forms macroergic bonds (ATP, creatine phosphate);
Part of proteins (phosphoproteins);
Part of carbohydrates (glucose-6ph, fructose-6ph, etc.);
Regulates the activity of enzymes (reactions of phosphorylation/dephosphorylation of enzymes, part of inositol triphosphate - a component of the inositol triphosphate system);
Participates in the catabolism of substances (phospholysis reaction);
Regulates the CBS because forms phosphate buffer. Neutralizes and removes protons in urine.

Bones and teeth contain 99% calcium. In bones, 99% of calcium is in the form of poorly soluble hydroxyapatite [Ca 10 (PO 4) 6 (OH) 2 H 2 O], and 1% is in the form of soluble phosphates;
Extracellular fluid 1%. Blood plasma calcium is presented in the form: a). free Ca 2+ ions (about 50%); b). Ca 2+ ions connected to proteins, mainly albumin (45%); c) non-dissociating calcium complexes with citrate, sulfate, phosphate and carbonate (5%). In the blood plasma, the concentration of total calcium is 2.2-2.75 mmol/l, and ionized calcium is 1.0-1.15 mmol/l;
Intracellular fluid contains 10,000-100,000 times less calcium than extracellular fluid.

Bones and teeth contain 85% phosphorus;
Extracellular fluid – 1% phosphorus. In the blood serum, the concentration of inorganic phosphorus is 0.81-1.55 mmol/l, phospholipid phosphorus 1.5-2 g/l;
Intracellular fluid – 14% phosphorus.

Exchange of calcium, magnesium and phosphates in the body
With food per day, calcium should be supplied - 0.7-0.8 g, magnesium - 0.22-0.26 g, phosphorus - 0.7-0.8 g. Calcium is poorly absorbed by 30-50%, phosphorus is well absorbed by 90%.
In addition to the gastrointestinal tract, calcium, magnesium and phosphorus enter the blood plasma from bone tissue during the process of its resorption. The exchange between blood plasma and bone tissue for calcium is 0.25-0.5 g/day, for phosphorus – 0.15-0.3 g/day.
Calcium, magnesium and phosphorus are excreted from the body through the kidneys with urine, through the gastrointestinal tract with feces and through the skin with sweat.
Regulation of exchange
The main regulators of calcium, magnesium and phosphorus metabolism are parathyroid hormone, calcitriol and calcitonin.
Parathyroid hormone
Parathyroid hormone (PTH) is a polypeptide of 84 AKs (about 9.5 kDa) synthesized in the parathyroid glands.
The secretion of parathyroid hormone is stimulated by low concentrations of Ca 2+, Mg 2+ and high concentrations of phosphates, and inhibited by vitamin D 3.
The rate of hormone breakdown decreases at low Ca 2+ concentrations and increases if Ca 2+ concentrations are high.
Parathyroid hormone acts on bones and kidneys. It stimulates the secretion of insulin-like growth factor 1 and cytokines by osteoblasts, which increase the metabolic activity of osteoclasts. In osteoclasts, the formation of alkaline phosphatase and collagenase is accelerated, which cause the breakdown of the bone matrix, resulting in the mobilization of Ca 2+ and phosphates from the bone into the extracellular fluid.
In the kidneys, parathyroid hormone stimulates the reabsorption of Ca 2+, Mg 2+ in the distal convoluted tubules and reduces the reabsorption of phosphates.
Parathyroid hormone induces the synthesis of calcitriol (1,25(OH) 2 D 3).
As a result, parathyroid hormone in the blood plasma increases the concentration of Ca 2+ and Mg 2+, and reduces the concentration of phosphates.
Hyperparathyroidism
In primary hyperparathyroidism (1:1000), the mechanism of suppression of parathyroid hormone secretion in response to hypercalcemia is disrupted. Causes may include tumor (80%), diffuse hyperplasia, or cancer (less than 2%) of the parathyroid gland.
Hyperparathyroidism causes:

destruction of bones, with the mobilization of calcium and phosphates from them. Increased risk of spinal fractures femur and bones of the forearm;
hypercalcemia, with increased reabsorption of calcium in the kidneys. Hypercalcemia leads to a decrease in neuromuscular excitability and muscle hypotension. Patients develop general and muscle weakness, fast fatiguability and pain in certain muscle groups;
formation of kidney stones with an increase in the concentration of phosphate and Ca 2 + in the renal tubules;
hyperphosphaturia and hypophosphatemia, with decreased reabsorption of phosphates in the kidneys;

In the skin, under the influence of UV radiation, most of cholecalciferol (vitamin D 3) is formed from 7-dehydrocholesterol. Not a large number of Vitamin D 3 comes from food. Cholecalciferol binds to a specific vitamin D-binding protein (transcalciferin), enters the blood and is transported to the liver.
In the liver, 25-hydroxylase hydroxylates cholecalciferol to calcidiol (25-hydroxycholecalciferol, 25(OH)D 3). D-binding protein transports calcidiol to the kidneys.
In the kidneys, mitochondrial 1?-hydroxylase hydroxylates calcidiol to calcitriol (1,25(OH)2D3), the active form of vitamin D3. Parathyroid hormone induces 1?-hydroxylase.

in intestinal cells induces the synthesis of Ca 2+ -transferring proteins, which ensure the absorption of Ca 2+ , Mg 2+ and phosphates;
in the distal tubules of the kidneys it stimulates the reabsorption of Ca 2+, Mg 2+ and phosphates;
at low Ca 2+ levels, it increases the number and activity of osteoclasts, which stimulates osteolysis;
with low levels of parathyroid hormone, stimulates osteogenesis.

suppresses osteolysis (reducing osteoclast activity) and inhibits the release of Ca 2 + from bone;
in the kidney tubules it inhibits the reabsorption of Ca 2+, Mg 2+ and phosphates;
inhibits digestion in the gastrointestinal tract,

pregnancy;
nutritional dystrophy;
rickets in children;
acute pancreatitis;
blockage of the biliary tract, steatorrhea;
renal failure;
infusion of citrated blood;

bone fractures;
polyarthritis;
multiple myelomas;
metastases malignant tumors in the bones;
overdose of vitamin D and Ca 2+;
obstructive jaundice;

rickets;
hyperfunction of the parathyroid glands;
osteomalacia;
renal acidosis

hypofunction of the parathyroid glands;
overdose of vitamin D;
renal failure;
diabetic ketoacidosis;
multiple myeloma;
osteolysis.

tissue breakdown;
infections;
uremia;
diabetic acidosis;
thyrotoxicosis;
chronic alcoholism.

Manganese is a cofactor for aminoacyl-tRNA synthetases.

Biological role of Na + , Cl - , K + , HCO 3 - - basic electrolytes, importance in the regulation of CBS. Metabolism and biological role. Anion difference and its correction.

Heavy metals (lead, mercury, copper, chromium, etc.), their toxic effects.

Increased chloride levels in the blood serum: dehydration, acute renal failure, metabolic acidosis after diarrhea and bicarbonate loss, respiratory alkalosis, head injury, adrenal hypofunction, with long-term use of corticosteroids, thiazide diuretics, hyperaldosteronism, Cushing's disease.
Decreased chloride content in the blood serum: hypochloremic alkalosis (after vomiting), respiratory acidosis, excessive sweating, nephritis with loss of salts (impaired reabsorption), head injury, a condition with an increase in the volume of extracellular flexibility, ulcerative ulcer, Addison's disease (hypoaldosteronism).
Increased excretion of chlorides in the urine: hypoaldosteronism (Addison's disease), salt-losing nephritis, increased salt intake, treatment with diuretics.
Decreased urinary chloride excretion: Loss of chlorides due to vomiting, diarrhea, Cushing's disease, end-phase renal failure, salt retention due to edema.
The normal calcium content in blood serum is 2.25-2.75 mmol/l.
The normal excretion of calcium in urine is 2.5-7.5 mmol/day.
Increased calcium levels in the blood serum: hyperparathyroidism, tumor metastases into bone tissue, multiple myeloma, decreased release of calcitonin, vitamin D overdose, thyrotoxicosis.
Decreased calcium levels in the blood serum: hypoparathyroidism, increased calcitonin secretion, hypovitaminosis D, impaired reabsorption in the kidneys, massive blood transfusion, hypoalbunemia.
Increased excretion of calcium in the urine: prolonged exposure to sunlight (hypervitaminosis D), hyperparathyroidism, tumor metastases into bone tissue, impaired reabsorption in the kidneys, thyrotoxicosis, osteoporosis, treatment with glucocorticoids.
Decreased excretion of calcium in the urine: hypoparathyroidism, rickets, acute nephritis (impaired filtration in the kidneys), hypothyroidism.
The iron content in the blood serum is normal mmol/l.
Increased iron content in blood serum: aplastic and hemolytic anemia, hemochromatosis, acute hepatitis and steatosis, liver cirrhosis, thalassemia, repeated transfusions.
Decreased iron content in blood serum: Iron-deficiency anemia, acute and chronic infections, tumors, kidney diseases, blood loss, pregnancy, impaired absorption of iron in the intestines.

Water is the medium in which most metabolic reactions take place. It is directly involved in metabolism. Water plays a certain role in the processes of thermoregulation of the body. Water delivers it to tissues and cells nutrients and removal of final metabolic products from them.

The excretion of water from the body is carried out by the kidneys - 1.2-1.5 l, skin - 0.5 l, lungs - 0.2-0.3 l. Water exchange is regulated by the neurohormonal system. Water retention in the body is promoted by the hormones of the adrenal cortex (cortisone, aldosterone) and the hormone of the posterior lobe of the pituitary gland, vasopressin. The thyroid hormone thyroxine increases the excretion of water from the body.
^

MINERAL METABOLISM

The composition of human and animal organs and tissues includes macroelements and microelements. The latter are contained in the body in very small quantities. In various living organisms, as in the human body, oxygen, carbon, hydrogen, and nitrogen are found in the greatest quantities. These elements, as well as phosphorus and sulfur, are part of living cells in the form various connections. Macroelements also include sodium, potassium, calcium, chlorine and magnesium. The following microelements were found in the body of animals: copper, manganese, iodine, molybdenum, zinc, fluorine, cobalt, etc. Iron occupies an intermediate position between macro- and microelements.

Minerals enter the body only with food. Then through the intestinal mucosa and blood vessels into the portal vein and the liver. The liver retains some minerals: sodium, iron, phosphorus. Iron is part of hemoglobin, participating in the transfer of oxygen, as well as in the composition of redox enzymes. Calcium is part of bone tissue and gives it strength. In addition, it plays an important role in blood clotting. Phosphorus, which is found in addition to free (inorganic) in compounds with proteins, fats and carbohydrates, is very useful for the body. Magnesium regulates neuromuscular excitability and activates many enzymes. Cobalt is part of vitamin B 12. Iodine is involved in the formation of thyroid hormones. Fluoride is found in dental tissues. Sodium and potassium are of great importance in maintaining blood osmotic pressure.

The metabolism of minerals is closely related to the metabolism of organic substances (proteins, nucleic acids, carbohydrates, lipids). For example, cobalt, manganese, magnesium, and iron ions are necessary for normal amino acid metabolism. Chlorine ions activate amylase. Calcium ions have an activating effect on lipase. The oxidation of fatty acids occurs more vigorously in the presence of copper and iron ions.
^

CHAPTER 12. VITAMINS

Vitamins are biologically active substances. Their absence or lack of food is accompanied by a sharp disruption of vital processes, leading to the occurrence of serious diseases. The need for vitamins is due to the fact that many of them are components of enzymes and coenzymes.

In my own way chemical structure vitamins are very diverse. They are divided into two groups: water-soluble and fat-soluble.

^ WATER SOLUBLE VITAMINS

1. Vitamin B 1 (thiamine, aneurin). Its chemical structure is characterized by the presence of an amine group and a sulfur atom. The presence of an alcohol group in vitamin B1 makes it possible to form esters with acids. By combining with two molecules of phosphoric acid, thiamine forms the ester thiamine diphosphate, which is a coenzyme form of the vitamin. Thiamine diphosphate is a coenzyme of decarboxylases that catalyze the decarboxylation of α-keto acids. In the absence or insufficient intake of vitamin B1 into the body, carbohydrate metabolism becomes impossible. Violations occur at the stage of utilization of pyruvic and α-ketoglutaric acids.

2. Vitamin B 2 (riboflavin). This vitamin is a methylated derivative of isoalloxazine bound to the 5-hydric alcohol ribitol.

In the body, riboflavin in the form of an ester with phosphoric acid is part of the prosthetic group of flavin enzymes (FMN, FAD), which catalyze biological oxidation processes, ensuring the transfer of hydrogen in the respiratory chain, as well as reactions of synthesis and breakdown of fatty acids.

3. Vitamin B 3 (pantothenic acid). Pantothenic acid is composed of -alanine and dioxydimethylbutyric acid, connected by a peptide bond. Biological significance pantothenic acid is that it is part of coenzyme A, which plays a huge role in the metabolism of carbohydrates, fats and proteins.

4. Vitamin B 6 (pyridoxine). By chemical nature, vitamin B 6 is a pyridine derivative. The phosphorylated derivative of pyridoxine is a coenzyme of enzymes that catalyze amino acid metabolism reactions.

5. Vitamin B 12 (cobalamin). The chemical structure of the vitamin is very complex. It contains four pyrrole rings. In the center there is a cobalt atom bonded to the nitrogen of the pyrrole rings.

Vitamin B 12 plays a large role in the transfer of methyl groups, as well as the synthesis of nucleic acids.

6. Vitamin PP (nicotinic acid and its amide). Nicotinic acid is a pyridine derivative.

Amide nicotinic acid is an integral part of the coenzymes NAD + and NADP +, which are part of dehydrogenases.

7. Folic acid (Vitamin B c). Isolated from spinach leaves (Latin folium - leaf). Folic acid contains para-aminobenzoic acid and glutamic acid. Folic acid plays an important role in the metabolism of nucleic acids and protein synthesis.

8. Para-aminobenzoic acid. It plays a large role in the synthesis of folic acid.

9. Biotin (vitamin H). Biotin is part of an enzyme that catalyzes the process of carboxylation (the addition of CO 2 to the carbon chain). Biotin is necessary for the synthesis of fatty acids and purines.

10. Vitamin C (ascorbic acid). The chemical structure of ascorbic acid is close to hexoses. A special feature of this compound is its ability to undergo reversible oxidation to form dehydroascorbic acid. Both of these compounds have vitamin activity. Ascorbic acid takes part in the redox processes of the body, protects the SH-group of enzymes from oxidation, and has the ability to dehydrate toxins.

^ FAT SOLUBLE VITAMINS

This group includes vitamins of groups A, D, E, K-, etc.

1. Vitamins of group A. Vitamin A 1 (retinol, antixerophthalmic) is close in its chemical nature to carotenes. It is a cyclic monohydric alcohol .

2. Vitamins of group D (antirachitic vitamin). In their chemical structure, vitamins of group D are close to sterols. Vitamin D 2 is formed from ergosterol in yeast, and Vitamin D 3 is formed from 7-de-hydrocholesterol in animal tissues under the influence of ultraviolet irradiation.

3. Vitamins of group E (, , -tocopherols). The main changes with vitamin E deficiency occur in the reproductive system (loss of the ability to bear a fetus, degenerative changes spermatozoa). At the same time, vitamin E deficiency causes damage to a wide variety of tissues.

4. Vitamins of group K. According to their chemical structure, vitamins of this group (K 1 and K 2) belong to naphthoquinones. A characteristic feature Vitamin deficiency K is the occurrence of subcutaneous, intramuscular and other hemorrhages and impaired blood clotting. The reason for this is a violation of the synthesis of the protein prothrombin, a component of the blood coagulation system.

ANTIVITAMINS

There are also structurally different antivitamins that are able to bind vitamins, depriving them of vitamin activity.
^

CHAPTER 13. HORMONES

Hormones are produced in the glands internal secretion(endocrine glands), which do not have excretory ducts and release their secretions directly into the bloodstream. The endocrine glands include the thyroid, parathyroid (near the thyroid), gonads, adrenal glands, pituitary gland, pancreas, and thymus glands.

Diseases that occur when the functions of one or another endocrine gland are disrupted are a consequence of either its hypofunction (reduced hormone secretion) or hyperfunction (excessive hormone secretion).

Hormones can be divided into three groups based on their chemical structure: protein hormones; hormones derived from the amino acid tyrosine, and hormones with a steroid structure.

^ PROTEIN HORMONES

These include hormones of the pancreas, anterior pituitary gland and parathyroid glands.

Pancreatic hormones - insulin and glucagon - are involved in the regulation of carbohydrate metabolism. In their action they are antagonists to each other. Insulin lowers and glucagon increases blood sugar levels.

Pituitary hormones regulate the activity of many other endocrine glands. These include:

Somatotropic hormone (GH) - growth hormone, stimulates cell growth, increases the level of biosynthetic processes;

Thyroid-stimulating hormone (TSH) - stimulates the activity of the thyroid gland;

Adrenocorticotropic hormone (ACTH) - regulates the biosynthesis of corticosteroids by the adrenal cortex;

Gonadotropic hormones regulate the function of the gonads.

^ HORMONES OF THE TYROSINE SERIES

These include thyroid hormones and adrenal medulla hormones. The main thyroid hormones are thyroxine and triiodothyronine. These hormones are iodinated derivatives of the amino acid tyrosine. With hypofunction of the thyroid gland, metabolic processes decrease. Hyperfunction of the thyroid gland leads to an increase in basal metabolism.

The adrenal medulla produces two hormones, adrenaline and norepinephrine. These substances increase blood pressure. Adrenaline has a significant effect on carbohydrate metabolism - it increases blood glucose levels.

^ STEROID HORMONES

This class includes hormones produced by the adrenal cortex and gonads (ovaries and testes). By chemical nature they are steroids. The adrenal cortex produces corticosteroids, they contain C 21 atom. They are divided into mineralocorticoids, of which the most active are aldosterone and deoxycorticosterone. and glucocorticoids - cortisol (hydrocortisone), cortisone and corticosterone. Glucocorticoids have big influence for the metabolism of carbohydrates and proteins. Mineralocorticoids mainly regulate the metabolism of water and minerals.

There are male (androgens) and female (estrogens) sex hormones. The former are C 19 -, and the latter C 18 -steroids. Androgens include testosterone, androstenedione, etc., and estrogens include estradiol, estrone and estriol. The most active are testosterone and estradiol. Sex hormones determine normal sexual development, the formation of secondary sexual characteristics, affect metabolism.

^ CHAPTER 14. BIOCHEMICAL FOUNDATIONS OF RATIONAL NUTRITION

In the problem of nutrition, three interrelated sections can be distinguished: rational nutrition, therapeutic and therapeutic-prophylactic. The basis is the so-called rational nutrition, since it is built taking into account the needs healthy person, depending on age, profession, climatic and other conditions. The basis of a balanced diet is balance and proper nutrition. Balanced diet is a means of normalizing the condition of the body and maintaining its high working capacity.

Carbohydrates, proteins, fats, amino acids, vitamins, and minerals enter the human body with food. The need for these substances varies and is determined by the physiological state of the body. A growing body needs more food. A person involved in sports or physical labor expends a large amount of energy, and therefore also needs more food than a sedentary person.

In human nutrition, the amount of proteins, fats and carbohydrates should be in the ratio 1:1:4, i.e., it is necessary for 1 g of protein. Consume 1 g of fat and 4 g of carbohydrates. Proteins should provide about 14% of calories daily ration, fats are about 31%, and carbohydrates are about 55%.

At the present stage of development of nutrition science, it is not enough to proceed only from the total consumption of nutrients. It is very important to establish the proportion of essential food components in the diet (essential amino acids, unsaturated fatty acids, vitamins, minerals, etc.). Modern teaching about human needs for food is expressed in the concept of a balanced diet. According to this concept, ensuring normal life activity is possible not only by supplying the body with an adequate amount of energy and protein, but also by observing rather complex relationships between numerous irreplaceable nutritional factors that are capable of exerting the maximum of their beneficial biological effects in the body. The law of balanced nutrition is based on ideas about the quantitative and qualitative aspects of the processes of food assimilation in the body, that is, the entire sum of metabolic enzymatic reactions.

The Institute of Nutrition of the USSR Academy of Medical Sciences has developed average data on the nutritional needs of an adult. Mainly, in determining the optimal ratios of individual nutrients, it is precisely this ratio of nutrients that is necessary on average to maintain the normal functioning of an adult. Therefore, when preparing general diets and evaluating individual products, it is necessary to focus on these ratios. It is important to remember that not only a deficiency of individual essential factors is harmful, but their excess is also dangerous. The reason for the toxicity of excess essential nutrients is probably associated with an imbalance in the diet, which in turn leads to a disruption of the biochemical homeostasis (constancy of the composition and properties of the internal environment) of the body and a disruption of cellular nutrition.

The given nutritional balance can hardly be transferred without changing the nutritional structure of people in different working and living conditions, people of different ages and genders, etc. Based on the fact that differences in energy and nutritional needs are based on the characteristics the course of metabolic processes and their hormonal and nervous regulation, it is necessary for persons of different ages and genders, as well as for persons with significant deviations from the average indicators of normal enzymatic status, to make certain adjustments to the usual presentation of the balanced nutrition formula.

The Institute of Nutrition of the USSR Academy of Medical Sciences has proposed standards for

calculating optimal diets for the population of our country.

These diets are differentiated relative to three climatic conditions

zones: northern, central and southern. However, recent scientific data indicate that such a division cannot be satisfactory today. Recent studies have shown that within our country the North must be divided into two zones: European and Asian. These zones differ significantly from each other in climatic conditions. At the Institute of Clinical and Experimental Medicine of the Siberian Branch of the Academy of Medical Sciences of the USSR (Novosibirsk), as a result of long-term studies, it was shown that in the conditions of the Asian North the metabolism of proteins, fats, carbohydrates, vitamins, macro- and microelements is restructured, and therefore there is a need to clarify human nutrition standards taking into account changes in metabolism. Currently, research is being conducted on a large scale in the field of rationalization of nutrition for the population of Siberia and Far East. A primary role in the study of this issue is given to biochemical research.

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 plays a role 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.

LECTURE COURSE

IN GENERAL BIOCHEMISTRY

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

Ekaterinburg,

LECTURE No. 24

Topic: Water-salt and mineral metabolism

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

Water-salt metabolism – exchange of water and the body’s main electrolytes (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 of 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.

A significant part of the body's chemical reactions 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:

Intravascular fluid;

Interstitial fluid (intercellular);

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, gall bladder, gastrointestinal tract and respiratory tract).

Liquids are intensively exchanged between pools. The movement of water from one sector to another occurs when osmotic pressure changes.

Osmotic pressure – This is the pressure created by all substances dissolved in water. The osmotic pressure of 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– 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 of various organs and tissues and blood plasma, the pH value, like osmotic pressure, is a relatively constant value.