Liver and carbohydrate metabolism. The liver crosses the metabolism of carbohydrates, lipids and proteins Other functions of the liver

The liver, being the central organ of metabolism, participates in maintaining metabolic homeostasis and is capable of interacting metabolic reactions of proteins, fats and carbohydrates.

The “connection” sites for the metabolism of carbohydrates and proteins are pyruvic acid, oxaloacetic and α-ketoglutaric acids from the tricarboxylic acid cycle, which can be converted in transamination reactions, respectively, into alanine, aspartate and glutamate. The process of converting amino acids into keto acids proceeds similarly.

Carbohydrates are even more closely related to lipid metabolism:

• NADPH molecules formed in the pentose phosphate pathway are used for the synthesis of fatty acids and cholesterol,
• glyceraldehyde phosphate, also formed in the pentose phosphate pathway, is included in glycolysis and converted to dihydroxyacetone phosphate,
• glycerol-3-phosphate, formed from dioxyacetone phosphate glycolysis, is sent for the synthesis of triacylglycerols. Also for this purpose, glyceraldehyde-3-phosphate, synthesized at the stage of structural rearrangements of the pentose phosphate pathway, can be used.
• “glucose” and “amino acid” acetyl-SCoA is capable of participating in the synthesis of fatty acids and cholesterol.

Carbohydrate metabolism

Carbohydrate metabolism processes actively occur in hepatocytes. Through the synthesis and breakdown of glycogen, the liver maintains the concentration of glucose in the blood. Active glycogen synthesis occurs after a meal, when the concentration of glucose in the blood of the portal vein reaches 20 mmol/l. Glycogen reserves in the liver range from 30 to 100 g. With short-term fasting, glycogenolysis, in case of prolonged fasting, the main source of blood glucose is gluconeogenesis from amino acids and glycerol.

The liver carries out interconversion sugars, i.e. conversion of hexoses (fructose, galactose) into glucose.

Active reactions pentose phosphate pathway provide the production of NADPH, necessary for microsomal oxidation and synthesis of fatty acids and cholesterol from glucose.

Lipid metabolism

If, during a meal, excess glucose enters the liver, which is not used for the synthesis of glycogen and other syntheses, then it is converted into lipids - cholesterol And triacylglycerols. Since the liver cannot store TAG, they are removed using very low density lipoproteins ( VLDL). Cholesterol is used primarily for the synthesis bile acids, it is also included in low-density lipoproteins ( LDL) And VLDL.

Under certain conditions - fasting, prolonged muscle exercise, type I diabetes mellitus, a diet rich in fat - the synthesis of ketone bodies, used by most tissues as an alternative source of energy, is activated in the liver.

Protein metabolism

More than half of the protein synthesized in the body per day occurs in the liver. The rate of renewal of all liver proteins is 7 days, while in other organs this value corresponds to 17 days or more. These include not only the proteins of the hepatocytes themselves, but also those going for “export”, which constitute the concept of “blood proteins” - albumins, many globulins, enzymes blood, as well as fibrinogen And clotting factors blood.

Amino acids undergo catabolic reactions with transamination and deamination, decarboxylation with the formation of biogenic amines. Synthesis reactions occur choline And creatine due to the transfer of a methyl group from adenosylmethionine. The liver utilizes excess nitrogen and incorporates it into urea.

The reactions of urea synthesis are closely related to the tricarboxylic acid cycle.

Close interaction between urea synthesis and the TCA cycle

Pigment exchange

The participation of the liver in pigment metabolism is the conversion of hydrophobic bilirubin into a hydrophilic form ( direct bilirubin) and its secretion into bile.

Pigment metabolism also includes the exchange gland, since iron is part of numerous hemoproteins throughout the body. Hepatocytes contain protein ferritin, which plays the role of iron depot, and is synthesized hepcidin, regulating the absorption of iron in the gastrointestinal tract.

Metabolic function assessment

In clinical practice, there are methods for assessing a particular function:

Participation in carbohydrate metabolism is assessed:

• By glucose concentration blood,
• by the slope of the glucose tolerance test curve,
• along the "sugar" curve after

Topic: "BIOCHEMISTRY OF THE LIVER"

1. Chemical composition of the liver: glycogen content, lipids, proteins, mineral composition.

2. The role of the liver in carbohydrate metabolism: maintaining a constant glucose concentration, synthesis and mobilization of glycogen, gluconeogenesis, main pathways for the conversion of glucose-6-phosphate, interconversion of monosaccharides.

3. The role of the liver in lipid metabolism: synthesis of higher fatty acids, acylglycerols, phospholipids, cholesterol, ketone bodies, synthesis and metabolism of lipoproteins, the concept of lipotropic effect and lipotropic factors.

4. The role of the liver in protein metabolism: synthesis of specific blood plasma proteins, formation of urea and uric acid, choline, creatine, interconversion of keto acids and amino acids.

5. Metabolism of alcohol in the liver, fatty degeneration of the liver due to alcohol abuse.

6. Neutralizing function of the liver: stages (phases) of neutralizing toxic substances in the liver.

7. Exchange of bilirubin in the liver. Changes in the content of bile pigments in the blood, urine and feces in various types of jaundice (suprahepatic, parenchymal, obstructive).

8. Chemical composition of bile and its role; factors contributing to the formation of gallstones.

31.1. Liver functions.

The liver is an organ that occupies a unique place in metabolism. Each liver cell contains several thousand enzymes that catalyze the reactions of numerous metabolic pathways. Therefore, the liver performs a number of metabolic functions in the body. The most important of them are:

• biosynthesis of substances that function or are used in other organs. These substances include blood plasma proteins, glucose, lipids, ketone bodies and many other compounds;
• biosynthesis of the final product of nitrogen metabolism in the body - urea;
• participation in digestive processes - synthesis of bile acids, formation and excretion of bile;
• biotransformation (modification and conjugation) of endogenous metabolites, drugs and poisons;
• release of certain metabolic products (bile pigments, excess cholesterol, neutralization products).

31.2 . The role of the liver in carbohydrate metabolism.

The main role of the liver in carbohydrate metabolism is to maintain a constant level of glucose in the blood. This is accomplished by regulating the ratio of the processes of formation and utilization of glucose in the liver.

Liver cells contain an enzyme glucokinase, catalyzing the phosphorylation reaction of glucose to form glucose-6-phosphate. Glucose-6-phosphate is a key metabolite of carbohydrate metabolism; the main routes of its transformation are presented in Figure 1.

31.2.1. Ways of glucose utilization. After eating, a large amount of glucose enters the liver through the portal vein. This glucose is used primarily for the synthesis of glycogen (the reaction diagram is shown in Figure 2). The glycogen content in the liver of healthy people usually ranges from 2 to 8% of the mass of this organ.

Glycolysis and the pentose phosphate pathway of glucose oxidation in the liver serve primarily as suppliers of precursor metabolites for the biosynthesis of amino acids, fatty acids, glycerol, and nucleotides. To a lesser extent, oxidative pathways for the conversion of glucose in the liver are sources of energy to ensure biosynthetic processes.

Figure 1. Major pathways for the conversion of glucose-6-phosphate in the liver. The numbers indicate: 1 - phosphorylation of glucose; 2 - hydrolysis of glucose-6-phosphate; 3 - glycogen synthesis; 4 - mobilization of glycogen; 5 - pentose phosphate pathway; 6 - glycolysis; 7 - gluconeogenesis.

Figure 2. Scheme of reactions of glycogen synthesis in the liver.

Figure 3. Scheme of glycogen mobilization reactions in the liver.

31.2.2. Pathways for glucose formation. In some conditions (during fasting, low-carbohydrate diet, prolonged physical activity), the body's need for carbohydrates exceeds the amount that is absorbed from the gastrointestinal tract. In this case, the formation of glucose is carried out using glucose-6-phosphatase, catalyzing the hydrolysis of glucose-6-phosphate in liver cells. The immediate source of glucose-6-phosphate is glycogen. The scheme of glycogen mobilization is presented in Figure 3.

Glycogen mobilization provides the human body with glucose needs during the first 12 to 24 hours of fasting. At a later date, gluconeogenesis - biosynthesis from non-carbohydrate sources - becomes the main source of glucose.

The main substrates for gluconeogenesis are lactate, glycerol and amino acids (with the exception of leucine). These compounds are first converted to pyruvate or oxaloacetate, key metabolites of gluconeogenesis.

Gluconeogenesis is the reverse process of glycolysis. In this case, the barriers created by irreversible reactions of glycolysis are overcome with the help of special enzymes that catalyze bypass reactions (see Figure 4).

Among other pathways of carbohydrate metabolism in the liver, it is worth noting the conversion of other dietary monosaccharides - fructose and galactose - into glucose.

Figure 4. Glycolysis and gluconeogenesis in the liver.

Enzymes that catalyze irreversible reactions of glycolysis: 1 - glucokinase; 2 - phosphofructokinase; 3 - pyruvate kinase.

Enzymes that catalyze the bypass reactions of gluconeogenesis: 4-pyruvate carboxylase; 5 - phosphoenolpyruvate carboxykinase; 6-fructose-1,6-diphosphatase; 7 - glucose-6-phosphatase.

31.3. The role of the liver in lipid metabolism.

Hepatocytes contain almost all enzymes involved in lipid metabolism. Therefore, liver parenchymal cells largely control the relationship between lipid consumption and synthesis in the body. Lipid catabolism in liver cells occurs mainly in mitochondria and lysosomes, biosynthesis occurs in the cytosol and endoplasmic reticulum. The key metabolite of lipid metabolism in the liver is acetyl-CoA, the main ways of formation and use of which are shown in Figure 5.

Figure 5. Formation and utilization of acetyl-CoA in the liver.

31.3.1. Metabolism of fatty acids in the liver. Dietary fats in the form of chylomicrons enter the liver through the hepatic artery system. Under the influence lipoprotein lipase, located in the endothelium of the capillaries, they are broken down into fatty acids and glycerol. Fatty acids that penetrate hepatocytes can undergo oxidation, modification (shortening or lengthening of the carbon chain, formation of double bonds) and are used for the synthesis of endogenous triacylglycerols and phospholipids.

31.3.2. Synthesis of ketone bodies. During β-oxidation of fatty acids in liver mitochondria, acetyl-CoA is formed, which undergoes further oxidation in the Krebs cycle. If there is a deficiency of oxaloacetate in the liver cells (for example, during fasting, diabetes), condensation of acetyl groups occurs to form ketone bodies (acetoacetate, β-hydroxybutyrate, acetone). These substances can serve as energy substrates in other tissues of the body (skeletal muscles, myocardium, kidneys, and during prolonged fasting - the brain). The liver does not utilize ketone bodies. With an excess of ketone bodies in the blood, metabolic acidosis develops. The formation diagram of ketone bodies is shown in Figure 6.

Figure 6. Synthesis of ketone bodies in liver mitochondria.

31.3.3. Formation and ways of using phosphatidic acid. The common precursor of triacylglycerols and phospholipids in the liver is phosphatidic acid. It is synthesized from glycerol-3-phosphate and two acyl-CoA - active forms of fatty acids (Figure 7). Glycerol-3-phosphate can be formed either from dihydroxyacetone phosphate (a metabolite of glycolysis) or from free glycerol (a product of lipolysis).

Figure 7. Formation of phosphatidic acid (scheme).

For the synthesis of phospholipids (phosphatidylcholine) from phosphatidic acid, a sufficient amount of food must be taken in lipotropic factors(substances that prevent the development of fatty liver). These factors include choline, methionine, vitamin B12, folic acid and some other substances. Phospholipids are included in lipoprotein complexes and take part in the transport of lipids synthesized in hepatocytes to other tissues and organs. The lack of lipotropic factors (with abuse of fatty foods, chronic alcoholism, diabetes) contributes to the fact that phosphatidic acid is used for the synthesis of triacylglycerols (insoluble in water). Impaired formation of lipoproteins leads to the fact that excess TAG accumulates in liver cells (fatty degeneration) and the function of this organ is impaired. The pathways of phosphatidic acid utilization in hepatocytes and the role of lipotropic factors are shown in Figure 8.

Figure 8. Use of phosphatidic acid for synthesistriacylglycerols and phospholipids. Lipotropic factors are indicated by *.

31.3.4. Cholesterol formation. The liver is the main site of endogenous cholesterol synthesis. This compound is necessary for the construction of cell membranes and is a precursor of bile acids, steroid hormones, and vitamin D3. The first two reactions of cholesterol synthesis resemble the synthesis of ketone bodies, but occur in the cytoplasm of the hepatocyte. Key enzyme in cholesterol synthesis - β -hydroxy-β -methylglutaryl-CoA reductase (HMG-CoA reductase) inhibited by excess cholesterol and bile acids according to the principle of negative feedback (Figure 9).

Figure 9. Cholesterol synthesis in the liver and its regulation.

31.3.5. Formation of lipoproteins. Lipoproteins are protein-lipid complexes, which include phospholipids, triacylglycerols, cholesterol and its esters, as well as proteins (apoproteins). Lipoproteins transport water-insoluble lipids to tissues. Hepatocytes produce two classes of lipoproteins - high-density lipoproteins (HDL) and very low-density lipoproteins (VLDL).

31.4. The role of the liver in protein metabolism.

The liver is an organ that regulates the entry and exit of nitrogenous substances into the body. In peripheral tissues, biosynthesis reactions constantly occur using free amino acids, or they are released into the blood during the breakdown of tissue proteins. Despite this, the level of proteins and free amino acids in the blood plasma remains constant. This occurs due to the fact that liver cells have a unique set of enzymes that catalyze specific protein metabolism reactions.

31.4.1. Ways of using amino acids in the liver. After eating protein foods, a large amount of amino acids enters the liver cells through the portal vein. These compounds can undergo a number of transformations in the liver before entering the general bloodstream. These reactions include (Figure 10):

a) the use of amino acids for the synthesis of proteins;

b) transamination - the path of synthesis of non-essential amino acids; also carries out the relationship between amino acid metabolism and gluconeogenesis and the general pathway of catabolism;

c) deamination - formation of α-keto acids and ammonia;

d) urea synthesis - a way to neutralize ammonia (see diagram in the section “Protein Metabolism”);

e) synthesis of non-protein nitrogen-containing substances (choline, creatine, nicotinamide, nucleotides, etc.).

Figure 10. Metabolism of amino acids in the liver (scheme).

31.4.2. Biosynthesis of proteins. Many blood plasma proteins are synthesized in liver cells: albumins(about 12 g per day), most α- And β-globulins, including transport proteins (ferritin, ceruloplasmin, transcortin, retinol binding protein and etc.). Many blood clotting factors (fibrinogen, prothrombin, proconvertin, proaccelerin etc.) are also synthesized in the liver.

31.5. Detoxifying function of the liver.

The liver neutralizes non-polar compounds of various origins, including endogenous substances, drugs and poisons. The process of neutralizing substances includes two stages (phases):

1)modification phase- includes reactions of oxidation, reduction, hydrolysis; optional for some connections;

2)conjugation phase- includes reactions of interaction of substances with glucuronic and sulfuric acids, glycine, glutamate, taurine and other compounds.

Neutralization reactions will be discussed in more detail in the section “Biotransformation of xenobiotics”.

31.6. Bile-forming function of the liver.

Bile is a yellowish-brown liquid secreted by liver cells (500-700 ml per day). The composition of bile includes: bile acids, cholesterol and its esters, bile pigments, phospholipids, proteins, minerals (Na+, K+, Ca2+, Cl-) and water.

31.6.1. Bile acids. They are products of cholesterol metabolism and are formed in hepatocytes. There are primary (cholic, chenodeoxycholic) and secondary (deoxycholic, lithocholic) bile acids. Bile contains mainly bile acids conjugated to glycine or taurine (for example, glycocholic acid, taurocholic acid, etc.).

Bile acids are directly involved in the digestion of fats in the intestines:

• have an emulsifying effect on dietary fats;
• activate pancreatic lipase;
• promote the absorption of fatty acids and fat-soluble vitamins;
• stimulate intestinal motility.

When the outflow of bile is disrupted, bile acids penetrate into the blood and urine.

31.6.2. Cholesterol. Excess cholesterol is removed from the body with bile. Cholesterol and its esters are present in bile in the form of complexes with bile acids (choleic complexes). In this case, the ratio of bile acids to cholesterol content (cholate ratio) must be no lower than 15. Otherwise, water-insoluble cholesterol precipitates and is deposited in the form of gallstones (cholelithiasis).

31.6.3. Bile pigments. Of the pigments in bile, conjugated bilirubin (mono- and diglucuronide of bilirubin) predominates. It is formed in liver cells as a result of the interaction of free bilirubin with UDP-glucuronic acid. At the same time, the toxicity of bilirubin decreases and its solubility in water increases; Conjugated bilirubin is then secreted into bile. If the outflow of bile is disrupted (obstructive jaundice), the content of direct bilirubin in the blood increases significantly, bilirubin is detected in the urine, and the content of stercobilin is reduced in feces and urine. For differential diagnosis of jaundice, see the section "Metabolism of complex proteins."

31.6.4. Enzymes. Of the enzymes found in bile, alkaline phosphatase should be noted first. This is an excretory enzyme synthesized in the liver. When the outflow of bile is disrupted, the activity of alkaline phosphatase in the blood increases.

Regulation of protein metabolism in the liver is carried out due to the intensive biosynthesis of proteins and the oxidation of amino acids. During the day, the human body produces about 80-100 g of protein, half of which is in the liver. During fasting, the liver is the fastest to use up its reserve proteins to supply other tissues with amino acids. Protein loss in the liver is approximately 20%; while in other organs it is no more than 4%. The proteins of the liver itself are normally completely renewed every 20 days. The liver sends most of the synthesized proteins into the blood plasma. When necessary (for example, during complete or protein fasting), these proteins also serve as sources of essential amino acids.

Having entered the liver through the portal vein, amino acids undergo a number of transformations, and a significant part of the amino acids is carried by the blood throughout the body and is used for physiological purposes. The liver ensures the balance of free amino acids in the body by synthesizing non-essential amino acids and redistributing nitrogen. Absorbed amino acids are primarily used as building materials for the synthesis of specific tissue proteins, enzymes, hormones and other biologically active compounds. A certain amount of amino acids undergoes breakdown with the formation of the final products of protein metabolism (CO2, H2O and NH3) and the release of energy.

All albumins, 75-90% of β-globulins (β 1 -antitrypsin, β 2 -macroglobulin - protease inhibitors, proteins of the acute phase of inflammation), 50% of plasma β-globulins are synthesized by hepatocytes. The liver synthesizes protein coagulation factors (prothrombin, fibrinogen, proconvertin, accelerator globulin, Christmas factor, Stewart-Prower factor) and part of the natural basic anticoagulants (antithrombin, protein C, etc.). Hepatocytes participate in the formation of some fibrinolysis inhibitors; erythropoiesis regulators - erythropoietins - are formed in the liver. The glycoprotein haptoglobin, which forms a complex with hemoglobin to prevent its excretion by the kidneys, is also of hepatic origin. This compound belongs to the proteins of the acute phase of inflammation and has peroxidase activity. Ceruloplasmin, also a glycoprotein synthesized by the liver, can be considered an extracellular superoxide dismutase, which helps protect cell membranes; Moreover, it stimulates the production of antibodies. A similar effect, only on cellular immunity, has transferrin, the polymerization of which is also carried out by hepatocytes.

Another carbohydrate-containing protein, but with immunosuppressive properties, can be synthesized by the liver - b-fetoprotein, an increase in the concentration of which in the blood plasma serves as a valuable marker of some tumors of the liver, testes and ovaries. The liver is the source of most of the complement system proteins.

In the liver, the most active exchange of protein monomers - amino acids occurs: synthesis of non-essential amino acids, synthesis of non-protein nitrogenous compounds from amino acids (creatine, glutathione, nicotinic acid, purines and pyrimidines, porphyrins, dipeptides, pantothenate coenzymes, etc.), oxidation of amino acids with the formation of ammonia, which is neutralized in the liver during the synthesis of urea.

So let's consider common pathways of amino acid metabolism. Common pathways for amino acid conversion in the liver include deamination, transamination, decarboxylation, and amino acid biosynthesis.

Deamination of amino acids. The existence of 4 types of amino acid deamination (cleavage of the amino group) has been proven (Appendix 17). The corresponding enzyme systems catalyzing these reactions were isolated and the reaction products were identified. In all cases, the NH 2 group of the amino acid is released in the form of ammonia. In addition to ammonia, deamination products include fatty acids, hydroxy acids and keto acids.

Transamination of amino acids. Transamination refers to reactions of intermolecular transfer of an amino group (NH2--) from an amino acid to a b-keto acid without the intermediate formation of ammonia. Transamination reactions are reversible and occur with the participation of specific aminotransferase enzymes, or transaminases.

Example of a transamination reaction:

Decarboxylation of amino acids. The process of removing the carboxyl group of amino acids in the form of CO 2. The resulting reaction products are biogenic amines. Decarboxylation reactions, unlike other processes of intermediate amino acid metabolism, are irreversible. They are catalyzed by specific enzymes - amino acid decarboxylases.

Neutralization of ammonia in the body. In the human body, about 70 g of amino acids per day undergo breakdown, and as a result of deamination and oxidation reactions of biogenic amines, a large amount of ammonia, which is a highly toxic compound, is released. Therefore, the concentration of ammonia in the body should be kept low. The level of ammonia in the blood normally does not exceed 60 µmol/l. Ammonia must undergo binding in the liver to form non-toxic compounds that are easily excreted in the urine.

One of the ways to bind and neutralize ammonia in the body is the biosynthesis of glutamine (and possibly asparagine). Glutamine and asparagine are excreted in urine in small quantities. Rather, they perform a transport function of carrying ammonia in a non-toxic form. Glutamine synthesis is catalyzed by glutamine synthetase.

The second and main way of neutralizing ammonia in the liver is the formation of urea, which will be discussed below in the urea-forming function of the liver.

In hepatocytes, individual amino acids undergo specific transformations. Taurine is formed from sulfur-containing amino acids, which is later included in paired bile acids (taurocholic, taurodeoxycholic), and can also serve as an antioxidant, binding the hypochlorite anion, stabilizing cell membranes; activation of methionine occurs, which in the form S- adenosylmethionine serves as a source of methyl groups in the reactions of the end of creatine genesis, choline synthesis for choline phosphatides (lipotropic substances).

Biosynthesis of non-essential amino acids. Any of the non-essential amino acids can be synthesized in the body in the required quantities. In this case, the carbon part of the amino acid is formed from glucose, and the amino group is introduced from other amino acids by transamination. Alania, aspartate, and glutamate are formed from pyruvate, oxaloacetate, and b-ketoglutarate, respectively. Glutamine is formed from glutamic acid by the action of glutamine synthetase:

Asparagine is synthesized from aspartic acid and glutamine, which serves as an amide group donor; The reaction is catalyzed by asparagine synthetase. Proline is formed from glutamic acid. Histidine (a partially non-essential amino acid) is synthesized from ATP and ribose: the purine part of ATP supplies the --N=CH--NH-- fragment for the imidazole cycle of histidine; the rest of the molecule is formed by ribose.

If there is no non-essential amino acid in food, cells synthesize it from other substances, and thereby maintain the full set of amino acids necessary for protein synthesis. If at least one of the essential amino acids is missing, protein synthesis stops. This is because the vast majority of proteins contain all 20 amino acids; therefore, if at least one of them is missing, protein synthesis is impossible.

Partially replaceable amino acids are synthesized in the body, but the rate of their synthesis is not sufficient to meet all the body's needs for these amino acids, especially in children. Conditionally essential amino acids can be synthesized from essential ones: cysteine ​​from methionine, tyrosine from phenylalanine. In other words, cysteine ​​and tyrosine are non-essential amino acids, provided there is sufficient dietary intake of methionine and phenylalanine.

Nitrogen balance

All proteins consist of nonessential and essential amino acids. Nonessential amino acids can be synthesized by body cells from other amino acids. Essential amino acids enter the body only with foods and cannot be synthesized from other compounds in the body. Complete proteins are of animal origin. A protein is considered incomplete if it lacks at least one essential amino acid.

Nitrogen is an essential component of the amino acid molecule. If you calculate the amount of nitrogen that entered the body and was excreted, you can estimate protein metabolism.

Definition 1

Nitrogen balance is the ratio of the amount of nitrogen taken into the body and removed from it.

On average, an adult needs 100-110 g of protein per day. Normally in the human body there is nitrogen balance- the amount of protein received is equal to the amount of protein broken down.

At an early age, accompanied by intensive growth, the amount of incoming protein exceeds its breakdown, that is, the child’s body receives more nitrogen than is removed from the body. This phenomenon is called positive nitrogen balance.

Nitrogen deficiency, or negative nitrogen balance, in which less nitrogen enters the body than is excreted, is observed in weakened patients, long-term starvation, and old age.

Conversions of proteins in the digestive tract

Proteins are not affected by specific enzymes in the mouth, pharynx and esophagus. Digestion begins in the stomach, where pepsin acts on proteins, breaking them down into polypeptides.

In the small intestine, polypeptides are broken down by enzymes of pancreatic and intestinal juices (chymotrypsin, trypsin, aminopeptidase, carboxypeptidase). As a result, amino acids are formed, which are absorbed through the intestinal villi into the blood.

Amino acids enter the liver through the bloodstream. Liver cells - hepatocytes, from part of the incoming amino acids, synthesize blood proteins, in particular, proteins of the coagulation system. The remaining amino acids travel through the general bloodstream to organs and tissues.

In cells, amino acids serve to form proteins specific to the body. Proteins are synthesized on ribosomes under the action of enzymes. The primary structure of a protein molecule is built with the participation of a DNA molecule. The formation of a secondary, tertiary structure occurs in the Golgi complex.

Functions of proteins in the body

The main functions of proteins in the body:

• plastic (building cellular and extracellular structures);
• enzymatic;
• regulatory (hormones – compounds of protein nature);
• energy (when 1 g of protein is broken down, 17.6 kJ of energy is released);
• specific functions (coagulation - as a result of the action of blood fibrinogen, contractile - the work of muscle tissue proteins actin and myosin, protective - blood immunoglobulins, etc.).

Proteins are not stored in the body, so when they are deficient, blood proteins or protein structures of tissues and organs are destroyed. The released amino acids serve as the starting material for the vital functions of the body.

Regulation of protein metabolism in the body

Protein metabolism is mainly influenced by neurohumoral factors:

• somatotropin (growth hormone) has an anabolic effect, promotes protein synthesis by increasing membrane permeability to amino acids, suppressing the synthesis of proteolytic enzymes, increasing the synthesis of ribonucleic acid;
• insulin stimulates the flow of amino acids into cells when their content in the blood is increased, increases the synthesis of tissue proteins;
• estrogens stimulate the synthesis of protein and ribonucleic acid in uterine cells;
• androgens stimulate the synthesis of protein and ribonucleic acid in many tissues of the body, including striated muscles;
• thyroxine and triiodothyronine exhibit an anabolic effect, stimulating protein synthesis;
• glucagon and glucocorticoids inhibit protein formation, especially in lymphoid and muscle tissues, and increase the process of nitrogen removal from the body.

The liver occupies a central place in metabolism. It has numerous functions, the most important of which are the following:

• 
  biosynthesis of blood proteins and lipoproteins,
• 
  bile formation,
• 
  metabolism of drugs and hormones,
• 
  deposition of iron, vitamins B12 and B9,
• 
  urea-forming function.

1. 
   regulatory-homeostatic (carbohydrates, proteins, lipids, vitamins, partially water-mineral compounds, pigment metabolism, non-protein nitrogen-containing substances);
2. 
   urea collecting;
3. 
   biliary;
4. 
   excretory;
5. 
   neutralizing (natural metabolic products and foreign substances).

The liver consists of 80% parenchymal cells, 16% reticuloendothelial cells, 4% endothelium of blood vessels.

^

Liver and carbohydrate metabolism

The energy needs of the liver itself, like other tissues of the body, are satisfied through intracellular catabolism of incoming glucose. Two different processes are involved in glucose catabolism: (3)

• 
  the glycolytic pathway converts 1 mole of glucose to 2 moles of lactate with the formation of 2 moles of ATP.
• 
  (4) The phosphogluconate pathway converts 1 mole of glucose into 6 moles of CO 2 and the formation of 12 moles of ATP.

In addition, glucose reactions can occur in the opposite direction, due to which (5) Glucose is synthesized through gluconeogenesis.

Phosphogluconate oxidation produces pentoses, which can be used in the synthesis of nucleides and nucleic acids.

In the liver, approximately 1/3 of glucose is oxidized via the phosphogluconate pathway, and the remaining 2/3 via the glycolytic pathway.

galactose, fructose, mannose

Glu Glu 6-ph Glycogen

(100-300g)
glycostatic

function

glycolysis

cholesterol (2 mol ATP + 2 lactate)
phosphogluconate pathway

(6CO 2 + 12NADPH+H +)
transformation

into fatty acids

^

Liver and lipid metabolism

(2) The liver synthesizes PL, a process that requires lipotropic substances (choline, methionine, B 12). Normally, the liver contains about 4% PL and 2% neutral fats. With fatty degeneration of the liver, the content of neutral fats can reach 40% (the common precursor phosphatidic acid, in case of deficiency of lipotropic substances, is used mainly for the synthesis of neutral fats). Increased synthesis of neutral fats and decreased synthesis of PL may be associated with ATP deficiency (with diffuse liver damage).

(3) The liver plays an important role in the synthesis of cholesterol, which is constantly synthesized from Acetyl CoA. With parenchymal lesions, the synthetic ability of the liver is reduced and this leads to hypocholesterolemia. The concentration of cholesterol esters especially decreases. On the contrary, with obstructive jaundice the concentration of cholesterol increases sharply, especially in uncomplicated cases when the function of the hepatocyte is not impaired.

The liver plays an important role in the synthesis (4) lipids, fatty acids , (5) lipolysis, ketone bodies.

P The liver occupies a key position in the processes of mobilization, processing and biosynthesis of fats. An imbalance of these opposing systems can lead to very serious metabolic disorders, as well as to the deposition of fat in the fiber (obesity) or in the cells of the liver itself (fatty liver).

Available Fat LP (blood plasma)

fat. who-you who-you E (beta oxidation )

Acetyl CoA ketone bodies

Cholesterone CO 2 + N 2 O + E

(90-95% endogenous cholesterol)

Gall

acids

(Cholesterol elimination pathway)
^

Liver and protein metabolism

The first and most obvious is related to the anatomical location of the organ. After consuming protein foods, liver cells are the first to take on the impact of the flow of amino acids and other digestion products entering through the portal vein system. Another anatomical advantage of the liver is its organic connection with the biliary tract, which allows the removal of some harmful end products of nitrogen metabolism directly into the gastrointestinal tract.

The second reason why the liver occupies a key position in nitrogen metabolism is that hepatocytes, unlike other cells in our body, contain a full set of enzymes involved in amino acid metabolism. The leading role in amino acid metabolism is associated with 3 functional processes:

1. 
   breakdown of the carbon skeleton with the formation of E and ensuring gluconeogenesis;
2. 
   formation of non-essential amino acids and nitrogenous bases of nucleic acids;
3. 
   neutralization of ammonia and other end products of uric acid metabolism, bile pigments, etc.

1. 
   the liver synthesizes many proteins for export, releasing them into the plasma (100% albumin, 75-90% alpha globulins, 50% beta globulins);
2. 
   the formation of intracellular enzymes in the liver affects metabolism throughout the body;
3. 
   Some liver proteins are capable of rapid breakdown, providing a labile reserve of amino acids during periods of insufficient nutrition.

That. the liver functions as an aminostat, regulating the supply of nitrogenous compounds and their release to the periphery, despite daily fluctuations in supply and demand, the level of proteins and free amino acids in the plasma remains constant.

participation in the measles cycle

(glu-ala)
liver proteins

transport Amino acids

in other tissues plasma proteins
NH 3 special products

Glu (heme, porphyrin, hormones,

nitrogenous bases and etc.)

intermediate

products of exchange

Acetyl-CoA lipids

CO 2 + H 2 O + E
^

Bile formation and excretory functions of the liver

Cholestasis syndrome - violation of biliary function.

Hepatocellular failure syndrome - violation of synthetic function.

Inflammatory syndrome
The role of the liver in the detoxification of various substances

Neutralization in the liver can occur of both endogenous toxic substances and foreign compounds. In two phases:

1. 
   oxidation, reduction, methylation:
2. 
   conjugation with UDPHA and FAPS.

The biochemical transformation of drugs and some foreign compounds in the liver involves a number of foreign enzyme systems that can affect many drugs that are diverse in their structure. These enzyme systems are built into the membrane of the endoplasmic reticulum of specialized liver cells - hepatocytes; the endoplasmic reticulum consists of communicating tubules, the main function of which is the assembly of enzyme complexes and the processing of foreign substances. The endoplasmic reticulum cannot be isolated from a cell without damaging it; during homogenization and centrifugation, the tubular system is destroyed and fragments of its membranes form tiny vesicles (microsomes). The function of microsomes serves as a source of enzymes that are used in the study of metabolism as drugs.

The process of processing drugs and food foreign substances in the liver includes reactions of relatively few types:

1. 
   oxidation;
2. 
   recovery;
3. 
   hydrolysis;
4. 
   binding (conjugation) with any other substance.

1. 
   inactivation in the main;
2. 
   lipophilic or fat-soluble substances are converted into hydrophilic ones, i.e. water-soluble compounds (easier to be removed by the kidneys and excreted).