The role of the liver in the human body can hardly be overestimated. After all, it was not for nothing that in ancient Babylon and China it was customary to treat this organ as a receptacle for the soul. In our time, it is called the second human heart, although from the point of view of anatomy this is not so.

The liver is the largest gland in the body and belongs to the digestive system. Due to its unique anatomy, it has a very high regenerative capacity.

The main functions of the human liver are to maintain homeostasis (the constancy of the internal environment) due to the provision of protein, fat, carbohydrate and pigment metabolism, as well as participation in the metabolism of vitamins. This organ is involved in detoxification, digestion and cleansing of the body. The biochemistry of the liver is very closely related to its functions.

Half of the protein that is synthesized in the body per day is formed in this organ. Blood proteins are produced here from amino acids - albumin, α and β-globulins, blood coagulation factors.

Also, the liver synthesizes and stores reserve amino acids, which are used when there is insufficient protein intake from food. If exhaustion, severe poisoning, bleeding occurs and the body needs protein, the liver gives up its reserve. The loss of protein during fasting can be up to 1/5 of the total mass, while in other organs only up to 1/25. Amino acids in the liver are completely renewed every three weeks.

One of the complex and multitasking proteins is AFP (α-fetoprotein). It is produced in the liver and has immune-suppressing properties. In the blood, this protein appears during pregnancy, ovaries, and testes.

Also, nonessential amino acids are actively synthesized in the liver.

Lipid metabolism

The liver also plays a significant role in fat metabolism.

She is responsible for such mutually reversible processes, such as:

1. synthesis of cholesterol from fatty acids;
2. synthesis of bile acids from cholesterol.

This gland is directly involved in the storage of fat. The formation of fatty acids is more active during the digestion of food, in the intervals between meals and during fasting. The intensity of the use of fats depends on the tension of the muscular work. The higher the activity, the more they are consumed.

The processes of regulating the metabolism of fats and carbohydrates depend on each other. With an excess of sugar, lipid production increases. If glucose enters the body in insufficient quantities, it is synthesized from proteins and fats. The conversion of carbohydrates into fats occurs when the cells of the organ are filled with glycogen to capacity.

Carbohydrate metabolism

In the liver cell (hepatocyte) glycogen is created from carbohydrates (glucose, galactose, fructose) - a reserve "for a rainy day". When the body needs energy, glycogen is converted back to glucose. It immediately enters the bloodstream and spreads to the cells, in which it turns into energy. The constant amount of carbohydrates in the blood is regulated mainly by the hormones of the pancreas.

Pigment exchange

The role of the liver in pigment metabolism is to convert free bilirubin into bound, with its subsequent excretion in the bile. Indirect bilirubin is produced by the breakdown of red blood cells and hemoglobin, which is part of the process of constant blood renewal. Free or indirect bilirubin is highly toxic. It undergoes a conjugation reaction and is processed into harmless - direct. This form of bilirubin is no longer toxic to the body.

Direct bilirubin is also called linked or conjugated. The liver takes an active part in removing this pigment from the body through the intestines. If the excretion of bilirubin in the body is impaired, jaundice develops.

If indirect bilirubin is increased in the analysis for liver biochemistry, this indicates an increased breakdown of red blood cells. This can be with hemolytic anemia, malaria.

Direct bilirubin is elevated in jaundice caused by gallstones.

The blood supply to the liver is unique due to its special anatomy. Only this gland receives blood directly from the artery and vein. It is thanks to this function of the liver that detoxification processes constantly occur in our body. This organ is deservedly called a "filter", which daily cleans the body of toxins and harmful substances by purifying the blood.

The barrier (detoxification, detoxification, antitoxic) function of the liver is perhaps the most important of the tasks it performs.

The deactivation (biotransformation) of toxic substances occurs in the liver's cells in the neutralizing function of the liver. They are synthesized by the body or come from the outside, for example, medicinal substances, chemical compounds foreign to the human body - xenobiotics.

The liver takes part in the reaction of inactivation of a number of biologically active compounds: estrogens, androgens, steroids, pancreatic hormones.

It binds ammonia due to the formation of urea and creatinine. In addition, this organ has the task of processing toxic substances (indole, skatole, cresol, phenol) formed during the work of the intestinal microflora. They are converted into harmless compounds by conjugation reactions. This is necessary in order to remove metabolic products from the body.

The protective function of the liver is also expressed in the phagocytosis of pathogens.

Digestive (metabolic) function

The irreplaceable role of this gland in digestion is the constant production of bile and sending it to the gallbladder for storage. It contains bile acids, direct bilirubin, cholesterol, water and other substances. Bile is formed in the liver cells - hepatocytes. In them, the function of its accumulation is performed by the Golgi apparatus.

After leaving the liver cells, bile is released first into the capillaries, then into the bile ducts. In the process of passing through the tubules, all the connections necessary for other organs are extracted from it, and only the substances necessary for digestion and the waste products of the body remain.

Due to the unique anatomy of the gallbladder, large amounts of bile can accumulate between meals. During meals, it enters the intestines in large portions, thereby improving the digestive process.

An important function of bile is to stimulate the intestines. Part of bile acids undergoes a conjugation reaction and, together with bile, is excreted into the duodenum. There, the acid emulsifies fats, facilitates the absorption of foods and their digestion.

As part of bile, direct bilirubin, decomposition products of toxic substances and xenobiotics are excreted from the liver.

An interesting feature of bile is the absence of enzymes in its composition.

Enzymatic function

Many biochemical reactions take place in the liver per day. Some products are often needed very quickly for such processes. For example, in extreme situations, energy is required, which can only be obtained from the breakdown of a glucose molecule. In such cases, liver enzymes come to our aid, significantly accelerating the biochemical reactions taking place in its cells.

The role of liver enzymes

Almost every biochemical reaction is catalyzed (accelerated) by a specific enzyme suitable only for it.

In this organ, enzymes such as ALT and AST are synthesized. GGT, ALP are partially synthesized. If liver enzymes "grow" in the analysis of liver biochemistry, this most often indicates that the organ is missing something and an urgent need to look for the cause.

The content of ALT in the blood in hepatitis, cirrhosis, jaundice, myocardial infarction, burns increases, and decreases - with a deficiency of vitamins of group B. liver enzymes should be considered in relation to each other. If ALT levels exceed AST, it is most likely liver disease. If, on the contrary, then hearts.

Other liver functions

Excretory (excretory) function

The excretory function of the liver consists in the excretion of bile together with other metabolic products into the bile ducts, followed by their entry into the intestinal lumen and excretion from the body.

Vitamin exchange

The liver is directly involved in the synthesis and absorption of fat-soluble vitamins (A, D, E, K), and also stores and removes their excess (A, D, K, C, PP) from the body. If during nutrition vitamins do not enter the body in sufficient quantities, it begins to consume them from its reserves.

Immune and allergic reactions

The liver takes part in the maturation of immune cells (immunopoiesis), and in immunological reactions. Also, the reaction of the body to allergens largely depends on it.

In conclusion, we can say that the liver is the most important digestive organ. It plays a huge role in the metabolic processes of the body and the synthesis of important compounds, if its work is disrupted, this affects all aspects of health.

The liver takes an active part in the synthesis and transformation of proteins (proteins). It is possible that this particular function is one of the vital ones.

In a person weighing 70 kg, the total amount of protein is about 14 kg, proteolysis and simultaneous proteosynthesis - 300-500 g / day. From amino acids of food proteins, 70-100 g of protein is synthesized, i.e. 50% of the total protein synthesis from amino acids; 30% of the protein is synthesized from the amino acids of the degrading protein of cells, 10% from the degrading protein of enzymes, 1% from plasma proteins; It uses 20% of the protein synthesized by the liver for its own purposes, 80% for other organs and tissues of the body. The concentration of amino acids in the serum serum has a regulating effect on protein synthesis. Synthesis is activated by hormones

thyroid gland, glucocorticoids and, possibly, insulin, inhibits this type of synthesis of glucocorticosteroids.

The breakdown of protein in the liver is rapid. Proteases and peptidases of lysosomes carry out proteolysis in an acidic medium without any particular species specificity. Proteolytic enzymes of the cytoplasm are active in a neutral environment and are more species specific. In experiments on dogs, it was proved that when eating protein-rich food, 57% of nitrogenous compounds are converted into urea, 6% is used in blood plasma, 4% goes to liver proteins and 23% goes to peripheral (extrahepatic) amino acid intake.

The liver synthesizes almost 100% albumin, 90% o, -globulins, 75% a 2 -globulins and 50% / 3-globulins.

Normally, the participation of the liver in the synthesis of gamma globulins is relatively small. In pathological conditions, the role of stellate reticuloendotheliocytes in the production of this protein increases; more and more importance is attached to the plasma cells of inflammatory liver infiltrates.

1.2.1. Proteins, including immunoglobulins

Albumin, The liver synthesizes 12-15 g of albumin daily. The half-life of albumin is 7-26 days. It plays an important role in maintaining normal oncotic blood pressure. Hypoalbuminemia contributes to the development of edema.

A significant part of the transport proteins-ligandins belongs to albumin. Some enzyme proteins are also albumin, in particular glutathione transferase, which plays an important role in transport within the hepatocyte. This ligand function of glutathione transferase concerns unconjugated bilirubin, cholesterol, free fatty acids, hormones, drugs. Violation of the transport function of albumin is not well understood.

Alpha-1-globulin. Half-life, -globulin 8-10 days. After hepatectomy, the first thing to do is to decrease the protein content. This type of protein includes a large number of lipoproteins and glycoproteins (acidic a, -glycoprotein - orosomucoid, er, -lipoprotein, g antitrypsin).

ALFA-2- globulin (a 7-globulin). This type of protein includes a large number of glycoproteins and lipoproteins (ceruloplasmin 2 -antithrombin, haptoglobin, 2 -macroglobulin, etc.).

Beta Globulin < fi -globulin). The £ -fraction includes trans-ferrin, hemapexin, ^ 2 ~ microglobulin, etc. An increase in the concentration of / 3 -globulins is observed in cholestasis.

TO a r ~ and ^ -globulins are metalloproteins that play

important biological role... The proteins associated with

the exchange of iron (transferrin, ferritin, siderophilin) ​​and copper

(ceruloplasmin). h

Iron-group metalloproteins are associated with the development of hemochromatosis. In this case, transferrin plays an important role -

a glycoprotein related to transport proteins that regulates the entry of iron into the cell. In hemochromatosis, iron saturation of transferrin increases sharply.

ferritin is a depositing protein that provides and controls the maintenance of a certain iron content in the cell. Under normal conditions, it prevents excess metal buildup in the cell. With an excessive intake of iron and a number of other disorders of its metabolism, the concentration of ferritin in the blood serum increases. This is observed in hemochromatosis, hepatocellular carcinoma, cirrhosis and acute liver necrosis. A decrease in ferritin concentration below 10 ng / 100 ml usually indicates an iron deficiency in the body.

An increase in iron concentrations in the liver is observed in diseases occurring with hyperferritinemia, as well as in late cutaneous porphyria, sprue, starvation, hemolytic anemias, repeated blood transfusions, after portocaval anastomoses are applied.

Copper group metalloproteins. About 90% of the copper in the blood serum is associated with ceruloplasmin, about 10% - with serum albumin (fragile). It is copper loosely bound to albumin that is captured by the sinusoidal pole of the hepatocyte. Part of it enters the smooth endoplasmic reticulum, where it combines with the protein part of ceruloplasmin previously synthesized in ribosomes and forms a full-fledged ceruloplasmin. Another part of the copper entering the hepatocyte is excreted by lysosomes into bile and further into the intestine.

In cases of the development of Wilson-Konovalov's disease (hepatocerebral dystrophy), both the synthesis of ceruloplasmin and the evacuation of copper by lysosomes are impaired. The causal relationship between these processes has not yet been clearly established. An increase in the concentration of copper not associated with ceruloplasmin leads to the excretion of copper by the kidneys. In this case, copper molecules are excreted together with amino acids, which entails a decrease in the concentration of copper in the blood serum and an increase in the amount of amino acids in the urine. A decrease in the concentration of ceruloplasmin in the blood serum is observed in Wilson-Konovalov disease.

Among glycoproteins, fibronectin has recently attracted attention. It is synthesized mainly by the liver. Stellate reticuloendotheliocytes are involved in this process. Fibronectin is a component of connective tissue that performs structural functions, it is consumed in the process of isolating fragments of hepatocytes and other cells. Lack of fibronectin can contribute to microembolic obstruction of the lungs and impairment of systemic microcirculation.

Gamma globulins are mainly immunoglobulins, with a half-life of 20-30 days.

Allocate 5 classes of immunoglobulins: IgA, IgG, IgD, IgE, IgM, Especially noticeable in liver diseases, the concentration of IgA, IgG and IgM of blood serum changes.

Immunoglobulin G (IgG) - the main immunoglobulin of blood serum - carries out protective functions against pathogenic microorganisms and toxins in the vascular bed, as well as in extra-vascular spaces, where it freely penetrates.

Immunoglobulin M (IgM - macroglobulin) is found mainly in the vascular bed. Plays an important protective role in bacteremia and viremia at an early stage of infection.

Immunoglobulin A (IgA) - serum IgA - makes up less than 50% of the immunoglobulin contained in the human body. Most of this immunoglobulin is contained in secretions (milk, bile, saliva, lacrimal fluid, secretions of the intestinal and respiratory tract). Protects mucous membranes from pathogenic microorganisms and potential autoallergens.

During a day, 160-400 mg of IgA secretions are secreted into the intestines with bile. This is about 10% of the total amount of IgA found in the intestine during this period. It is assumed that most of this IgA is synthesized in the mucous membrane of the biliary tract. Locally produced IgA plays an important role in the resistance of the smallest bile ducts to various injuries.

Serum immunoglobulin concentrations fluctuate in a number of liver diseases. Chronic active hepatitis (CAH) and active forms of liver cirrhosis occur with poly-clonal hyperimmunoglobulinemia, that is, in these diseases, there is an increase in the content of the main classes of immunoglobulins (IgA, IgG, IgM), especially one of them. In particular, viral diseases occur mainly with an increase in the content of IgM and IgG, alcoholic - IgA, primary biliary cirrhosis - IgM. In most of these patients, hypergammaglobulinemia is simultaneously noted. Congenital and acquired IgA deficiencies often aggravate the severity of chronic progressive liver diseases, as well as cholestasis of various origins.

1.2.2. Metabolism of amino acids, urea, ammonia and uric acid

Amino acids. Maintaining the relative constancy of the amino acid composition of the blood is one of the important functions of the liver.

In some diseases (for example, hepatocerebral dystrophy), increased hyperaminoaciduria is observed. In individual forms of major liver failure, an increase in the concentration of a number of blood serum amino acids - phenylalanine, tyrosine, tryptophan, methionine, and a simultaneous decrease in the concentration of branched-chain amino acids - shaft and on, leucine, isoleucine is revealed.

These changes are due to the peculiarities of the destruction of various groups of amino acids.

The first group - essential amino acids, with the exception of branched ones, are destroyed only in the liver. These include

phenylalanine, tryptophan, tyrosine and methionine. The immediate cause of this phenomenon is a drop in the concentration of enzymes: phenylalanine hydroxylase, tryptophan pyrrolase contained in hepatocytes.

The second group is branched-chain amino acids, which are destroyed mainly in the muscles (much less in the liver). The reason for the decrease in the concentration of these amino acids in the blood serum of patients with liver cirrhosis, especially after the imposition of porto-caval anastomoses, is not entirely clear. It is possible that hyperinsulinemia leads to greater absorption by the muscles.

The third group is non-essential amino acids, which are destroyed both in the liver and in the muscles.

Urea. The formation of urea occurs mainly in the liver. In this way, the transformation of poisonous fragments of a protein molecule (amino groups, etc.) into a practically non-toxic substance - urea is achieved.

For the synthesis of 1 mole of urea, 2 moles of bicarbonate are consumed, and thus the pH decreases. The synthesis of urea is one of the stable functions of the liver. Under normal conditions, no more than one-third of the potential power of the liver is used. Therefore, a decrease in serum urea concentrations is rarely observed. This pattern concerns the total production of urea. Violation of individual stages of its synthesis may not sharply violate the total concentration of urea in blood serum, but lead to an increase in the concentrations of toxic products formed at individual stages of synthesis of the urea molecule.

Similar disorders are observed, for example, with Reye's syndrome. The defeat of the mitochondria of hepatocytes and the enzymes localized in them, participating in the synthesis of urea, leads to the sharpest hyperammonemia and the development of encephalopathy.

Another product of ammonia neutralization is glutamine. Its synthesis is carried out not only in the liver. The difference between glutamine synthesis and urea synthesis is that the former is synthesized even at low ammonia concentrations, while the latter is only synthesized at sufficiently high ammonia concentrations.

At low pH, the breakdown of glutamine occurs, at high pH - vigorous synthesis of urea. Both processes are aimed at stabilizing the pH level under normal conditions.

It has been suggested that the kidneys mainly compensate for acidosis, and the liver for alkalosis.

Ammonia. During the deamination of nitrogenous compounds, primarily amino acids, ammonia is formed. When 100 g of protein is destroyed, about 20 g of ammonia is formed. Ammonia refers to both non-ionized NH3 and ionized NH4. High concentrations of ammonia in blood serum and tissues have highly toxic properties, while the body is adapted to normal concentrations of NH3. Ammonia is one of the raw materials for the synthesis of urea.

There are two main causes of hyperammonemia - excess

accurate uptake of NH3 from the intestine and reduced conversion of ammonia in the liver. Basically, hyperammonemia is observed in liver diseases, especially severe ones (Reye's syndrome, etc.). Congenital defects of enzyme systems that convert ammonia (defects in lysine dehydrogenase, methylmalonylmutase, etc.) are observed incomparably less frequently.

Uric acid is usually formed as the end product of the exchange of purine compounds. The most stable hyperuricemia occurs with gout. The liver is involved in the exchange of purines, and in a number of liver diseases, primarily alcoholic, hyperuricemia is observed. More often it follows acute alcohol intoxication. In the increased production of uric acid, the induction of such hepatocyte enzymes as xanthine oxidase and glutathione reductase plays an important role.

Without liver involvement in protein metabolism the body can do no more than a few days, then death occurs. The most important functions of the liver in protein metabolism include the following.

1. Deamination of amino acids.
2. Formation of urea and extraction of ammonia from body fluids.
3. Formation of blood plasma proteins.
4. Mutual transformation of various amino acids and synthesis of other compounds from amino acids.

Preliminary deamination amino acids are necessary for their use in obtaining energy and converting them into carbohydrates and fats. In small amounts, deamination is also carried out in other tissues of the body, especially in the kidneys, but these processes are not comparable in importance with the deamination of amino acids in the liver.

The formation of urea in the liver helps to extract ammonia from body fluids. A large amount of ammonia is formed in the process of deamination of amino acids, additional amount of it is constantly formed by bacteria in the intestines and absorbed into the blood. In this regard, if urea is not formed in the liver, then the concentration of ammonia in the blood plasma begins to increase rapidly, which leads to hepatic coma and death. Even in the case of a sharp decrease in blood flow through the liver, which sometimes occurs due to the formation of a shunt between the portal and vena cava, the level of ammonia in the blood rises sharply, creating conditions for toxicosis.

Everything essential proteins of blood plasma, with the exception of some gamma globulins, are produced by liver cells. Their number is approximately 90% of all plasma proteins. The rest of the gamma globulins are antibodies produced mainly by the plasma cells of the lymphoid tissue. The maximum rate of protein formation by the liver is 15-50 g / day, so if the body loses about half of the plasma proteins, their amount can be restored within 1-2 weeks.

It should be borne in mind that depletion of plasma proteins blood is the reason for the rapid onset of mitotic divisions of hepatocytes and an increase in the size of the liver. This effect is combined with the release of plasma proteins by the liver, which continues until the concentration of proteins in the blood returns to normal values. In chronic liver diseases (including cirrhosis), the level of proteins in the blood, especially albumin, can drop to very low values, which is the reason for the appearance of generalized edema and ascites.

Among the most important liver functions refers to its ability to synthesize some amino acids along with chemical compounds, which include amino acids. For example, the so-called nonessential amino acids are synthesized in the liver. In the process of such synthesis, keto acids are involved, which have a similar chemical structure to amino acids (excluding oxygen in the keto position). Amino radicals go through several stages of transamination, moving from the amino acids present in the nadichi into keto acids to the place of oxygen in the keto position.

Biological chemistry Lelevich Vladimir Valerianovich

The role of the liver in carbohydrate metabolism

The main role of the liver in carbohydrate metabolism is to maintain normal blood glucose levels - that is, in the regulation of normoglycemia.

This is accomplished through several mechanisms.

1. The presence of the enzyme glucokinase in the liver. Glucokinase, like hexokinase, phosphorylates glucose to glucose-6-phosphate. It should be noted that glucokinase, unlike hexokinase, is contained only in the liver and β-cells of the islets of Langerhans. The activity of glucokinase in the liver is 10 times higher than that of hexokinase. In addition, glucokinase, in contrast to hexokinase, has a higher Km for glucose (i.e., a lower affinity for glucose).

After a meal, the glucose content in the portal vein rises sharply and reaches 10 mmol / l or more. An increase in the concentration of glucose in the liver causes a significant increase in glucokinase activity and increases the uptake of glucose by the liver. Due to the synchronous work of hexokinase and glucokinase, the liver quickly and efficiently phosphorylates glucose to glucose-6-phosphate, providing normoglycemia in the general bloodstream. Further, glucose-6-phosphate can be metabolized in several ways (Fig. 28.1).

2. Synthesis and breakdown of glycogen. Liver glycogen acts as a glucose depot in the body. After a meal, excess carbohydrates are deposited in the liver in the form of glycogen, the level of which is approximately 6% of the liver weight (100–150 g). In the intervals between meals, as well as during the period of "night fast" replenishment of the pool of glucose in the blood due to absorption from the intestine does not occur. Under these conditions, the breakdown of glycogen to glucose is activated, which maintains the level of glycemia. Glycogen stores are depleted by the end of the 1st day of fasting.

3. In the liver, gluconeogenesis is actively proceeding - the synthesis of glucose from non-carbohydrate precursors (lactate, pyruvate, glycerol, glycogenic amino acids). Thanks to gluconeogenesis in the body of an adult, about 70 g of glucose is formed per day. The activity of gluconeogenesis increases sharply during fasting on the 2nd day, when the reserves of glycogen in the liver are exhausted.

Thanks to gluconeogenesis, the liver participates in the measles cycle - the process of converting lactic acid produced in muscles into glucose.

4. The liver converts fructose and galactose into glucose.

5. Glucuronic acid is synthesized in the liver.

Rice. 28.1. Involvement of glucose-6-phosphate in carbohydrate metabolism