Tag synthesis is energy storage. Reactions for the synthesis of tags from phosphatidic acid Lipid metabolism or cholesterol indicators

The level of TAG in the blood can vary significantly during the day. Hypertriglyceridemia can be physiological or pathological. Physiological hypertriglyceridemia occurs after a meal and may last, depending on the nature and amount of food taken. Physiological hypertriglyceridemia also occurs in the 2-3 trimester of pregnancy.

Pathological hypertriglyceridemia pathogenetically can be divided into primary and secondary. Primary hypertriglyceridemia may be due to genetic disorders of lipoprotein metabolism or overeating. Secondary hypertriglyceridemia occurs as a complication of the underlying pathological process. In clinical practice, the study of TAG is carried out to classify congenital and metabolic disorders of lipid metabolism, as well as to identify risk factors for atherosclerosis and coronary heart disease.

• familial hypertriglyceridemia (phenotype IV);
• complex familial hyperlipidemia (phenotype II b);
• familial dysbetalipoproteinemia (phenotype III);
• chylomicronemia syndrome (phenotype I);
• deficiency of LCAT (lecithincholesterol acyltransferase).

• ischemic heart disease, myocardial infarction, atherosclerosis;
• hypertonic disease;
• obesity;
• viral hepatitis and cirrhosis of the liver (alcoholic, biliary), obstruction of the biliary tract;
• diabetes;
• hypothyroidism;
• nephrotic syndrome; m
• acute and chronic pancreatitis;
• taking oral contraceptives, beta blockers, thiazide diuretics;
• pregnancy;
• glycogenosis;
• thalassemia.

Lowering triglycerides:

• hypolipoproteinemia;
• hyperthyroidism;
• hyperparathyroidism;
• malnutrition;
• malabsorption syndrome;
• intestinal lymphangiectasia;
• chronic obstructive pulmonary disease;
• taking cholestyramine, heparin, vitamin C, progestins.

BIOSYNTHESIS OF TRIGLYCERIDES

It is known that the rate of fatty acid biosynthesis is largely determined by the rate of formation of triglycerides and phospholipids, since free fatty acids are present in tissues and blood plasma in small amounts and do not normally accumulate.

Synthesis of triglycerides comes from glycerol and fatty acids (mainly stearic, palmitic and oleic). The pathway of biosynthesis of triglycerides in tissues proceeds through the formation of α-glycerophosphate (glycerol-3-phosphate) as an intermediate.

In the kidneys, as well as in the intestinal wall, where the activity of the enzyme glycerol kinase is high, glycerol is phosphorylated at the expense of ATP with the formation of glycerol-3-phosphate:

In adipose tissue and muscles, due to the very low activity of glycerol kinase, the formation of glycerol-3-phosphate is mainly associated with the processes of glycolysis and glycogenolysis. It is known that dihydroxyacetone phosphate is formed during the glycolytic breakdown of glucose (see Chapter 10). The latter, in the presence of cytoplasmic glycerol-3-phosphate dehydrogenase, is able to turn into glycerol-3-phosphate:

It has been noted that if the glucose content in adipose tissue is reduced (for example, during starvation), then only a small amount of glycerol-3-phosphate is formed and free fatty acids released during lipolysis cannot be used for triglyceride resynthesis, so fatty acids leave adipose tissue. On the contrary, the activation of glycolysis in adipose tissue contributes to the accumulation of triglycerides in it, as well as their constituent fatty acids. In the liver, both pathways for the formation of glycerol-3-phosphate are observed.

The glycerol-3-phosphate formed in one way or another is sequentially acylated by two molecules of the CoA derivative of the fatty acid (i.e., the "active" forms of the fatty acid - acyl-CoA). As a result, phosphatidic acid (phosphatidate) is formed:

As noted, the acylation of glycerol-3-phosphate proceeds sequentially; in 2 stages. First, glycerol-3-phosphate acyltransferase catalyzes the formation of lysophosphatidate (1-acylglycerol-3-phosphate), and then 1-acylglycerol-3-phosphate acyltransferase catalyzes the formation of phosphatidate (1,2-diacylglycerol-3-phosphate).

The 1,2-diglyceride is then acylated by a third acyl-CoA molecule and converted to a triglyceride (triacylglycerol). This reaction is catalyzed by diacylglycerol acyltransferase:

The synthesis of triglycerides (triacylglycerols) in tissues takes into account two pathways for the formation of glycerol-3-phosphate and the possibility of triglyceride synthesis in the wall of the small intestine from β-monoglycerides coming from the intestinal cavity in large quantities after the breakdown of dietary fats. On fig. 11.6 shows the glycerophosphate, dihydroxyacetone phosphate, and β-monoglyceride (monoacylglycerol) pathways for triglyceride synthesis.

Rice. 11.6. Biosynthesis of triglycerides (triacylglycerols).

It has been established that most of the enzymes involved in the biosynthesis of triglycerides are located in the endoplasmic reticulum, and only a few, for example, glycerol-3-phosphate acyltransferase, are in mitochondria.

TAG synthesis is energy storage

Synthesis of triacylglycerols

The synthesis of TAG consists in the dephosphorylation of phosphatidic acid derived from glycerol-3-phosphate and the addition of an acyl group.

Reactions for the synthesis of TAG from phosphatidic acid

After the synthesis of TAGs, they are evacuated from the liver to other tissues, more precisely, to tissues that have lipoprotein lipase on the endothelium of their capillaries (Transport of TAGs in the blood). The transport form is VLDL. Strictly speaking, the cells of the body need only fatty acids, all other components of VLDL are not necessary.

TAG synthesis increases when at least one of the following conditions is met, which ensures the appearance of an excess of acetyl-SCoA:

• availability of a source of "cheap" energy. For example,

1) a diet rich in simple carbohydrates (glucose, sucrose). At the same time, the concentration of glucose in the liver and adipocytes increases sharply after eating, it is oxidized to acetyl-SCoA, and under the influence of insulin, fat synthesis actively occurs in these organs.

2) the presence of ethanol, a high-energy compound that oxidizes to acetyl-SCoA. "Alcoholic" acetyl is used in the liver for fat synthesis under normal nutrition. An example is "beer obesity".

an increase in the concentration of fatty acids in the blood. For example, with increased lipolysis in fat cells under the influence of any substances (pharmaceuticals, caffeine, etc.), with emotional stress and the absence (!) of muscle activity, the flow of fatty acids into hepatocytes increases. Here, as a result, an intensive synthesis of TAG occurs.

high concentrations of insulin and low concentrations of glucagon - after ingestion of high-carbohydrate and fatty foods.

Fat synthesis (TAG)

The metabolism of fats or TAGs includes several stages: 1). Synthesis of fats (from glucose, endogenous fats), 2). Deposition of fats, 3). Mobilization.

In the body, fats can be synthesized from glycerol and from glucose. The main 2 substrates for the synthesis of fats:

2) acylCoA (activated FA).

Synthesis of TAG occurs through the formation of phosphatidic acid.

α-GP in the human body can be formed in two ways: in organs in which the enzyme glycerol kinase is active, GP can be formed from glycerol, in organs where the activity of the enzyme is low, GP is formed from glycolysis products (i.e. from glucose).

If the reduced form of NAD (NADH + H) enters into the reaction, then this is a reaction

recovery and the enzyme is named after the product + "DG".

TAG biosynthesis proceeds most intensively in the liver and adipose tissue. In fatty

tissue, TAG synthesis proceeds from HC, i.e. part of the glucose ingested with food

turn into fat (when more carbohydrates are supplied than necessary for

replenishment of glycogen stores in the liver and muscles).

Fats synthesized in the liver (in two ways) are packaged into LOIP particles,

enter the blood > LP-lipase, which hydrolyzes TAGs or fats from these particles into

LCD and glycerin. FAs enter the adipose tissue, where they are deposited in the form of fats, or

are used as an energy source by organs and tissues (p-oxidation), and glycerol

enters the liver, where it can be used for the synthesis of TAG or phospholipids.

In adipose tissue, fats are deposited, which are formed from glucose, glucose gives

both or 2 substrates for fat synthesis.

After a meal (absorption period) f concentration of glucose in the blood, |

insulin concentration, insulin activates:

1. transport of glucose into adipocytes,

Activates the synthesis of fat in adipose tissue and its deposition - > There are 2 sources of fats to be deposited in adipose tissue:

1. exogenous (TAG from chylomicrons and intestinal VLDL that carry food

2. endogenous fats (from liver VLDL and TAGs formed in the fatty

Fat mobilization is the hydrolysis of fats in adipocytes to fatty acids and glycerol, under the action of hormone-dependent TAG-lipase, which is located in cells and is activated depending on the body's needs for energy sources (in the post-absorptive period, i.e. in the intervals between meals , during starvation, stress, prolonged physical work, i.e. activated by adrenaline, glucagon and somatotropic hormone (STH).

With prolonged fasting, the concentration of glucagon increased. This leads to a decrease in the synthesis of fatty acids, an increase in β-oxidation, an increase in the mobilization of fats from the depot, an increase in the synthesis of ketone bodies, and an increase in gluconeogenesis.

The difference between the action of insulin in adipose tissue and the liver:

The concentration of insulin in the blood leads to the activity of PFP, the synthesis of fatty acids, glycolysis (glucokinase, phosphofructokinase (PFK), pyruvate kinase - enzymes of glycolysis; glucose-6-DG - enzyme PFP; acetylCoAcarboxylase - enzyme synthesis of fatty acids).

In adipose tissue, LP-lipase and fat deposition are activated, the entry of glucose into adipocytes and the formation of fats from it, which are also deposited, are activated.

There are 2 forms of deposited energy material in the human body:

1. glycogen; 2. TAG or neutral fats.

They differ in reserves and order of mobilization. Glycogen in the liver is off, maybe up to 200, fats are normal

Glycogen is enough (as an energy source) for 1 day of fasting, and fat - for 5-7 weeks.

During fasting and physical activity, glycogen stores are primarily used, then the rate of fat mobilization gradually increases. short-term physical

loads are provided with energy, due to the breakdown of glycogen, and during prolonged physical exertion, fats are used.

With a normal diet, the amount of fat in adipose tissue is constant, but the fats are constantly updated. With prolonged fasting and physical exertion, the rate of fat mobilization is greater than the rate of deposition à reduce the amount of deposited fat. (weight loss). If the rate of mobilization is lower than the rate of deposition - obesity.

Causes: the discrepancy between the amount of food consumed and the body's energy expenditure, and since the mobilization and deposition of fats are regulated by hormones, obesity is a characteristic sign of endocrine diseases.

Cholesterol exchange. Biochemical basis of atherosclerosis. The main functions of cholesterol in the body:

1. main: most of the cholesterol is used to build cell membranes;

2. Xc serves as a precursor of bile acids;

3. serves as a precursor of steroid hormones and vitamin D3 (sex

hormones and hormones of the adrenal cortex).

In the body, Xc accounts for the bulk of all steroids.

140g. Chc is synthesized mainly in the liver (-80%), in the small intestine (-10%), in the skin (-5%), the rate of Chc synthesis in the body depends on the amount of exogenous Chc, if more than 1 g of Chc is supplied with food (2- 3d) the synthesis of one's own endogenous cholesterol is inhibited if cholesterol is supplied little (vegetarians) the rate of synthesis of endogenous cholesterol |. Violation in the regulation of the synthesis of Chs (as well as the formation of its transport forms - > hypercholesterolemia -" atherosclerosis -\u003e IHD - myocardial infarction). The intake rate of Xc> 1g (eggs, butter (butter), liver, brain).

Blood chemistry

General information

A biochemical blood test is one of the most popular research methods for patients and doctors. If you clearly know what a biochemical blood test from a vein shows, you can identify a number of serious ailments in the early stages, including viral hepatitis, diabetes mellitus, and malignant neoplasms. Early detection of such pathologies makes it possible to apply the correct treatment and cure them.

The nurse collects blood for examination for several minutes. Each patient must understand that this procedure does not cause discomfort. The answer to the question of where blood is taken from for analysis is unequivocal: from a vein.

Speaking about what a biochemical blood test is and what is included in it, it should be noted that the results obtained are actually a kind of reflection of the general condition of the body. Nevertheless, trying to understand on your own whether the analysis is normal or there are certain deviations from the normal value, it is important to understand what LDL is, what is CPK (CPK - creatine phosphokinase), to understand what urea (urea), etc.

General information about the analysis of blood biochemistry - what it is and what you can learn by doing it, you will receive from this article. How much it costs to conduct such an analysis, how many days it takes to get the results, you should find out directly in the laboratory where the patient intends to conduct this study.

How is the preparation for biochemical analysis?

Before you donate blood, you need to carefully prepare for this process. For those who are interested in how to properly pass the analysis, you need to take into account a few fairly simple requirements:

• you need to donate blood only on an empty stomach;
• in the evening, on the eve of the upcoming analysis, you can not drink strong coffee, tea, consume fatty foods, alcoholic beverages (it is better not to drink the latter for 2-3 days);
• do not smoke for at least an hour before the analysis;
• a day before the test, you should not practice any thermal procedures - go to the sauna, bath, and a person should not subject himself to serious physical exertion;
• you need to take laboratory tests in the morning, before any medical procedures;
• a person who is preparing for analysis, having come to the laboratory, should calm down a little, sit for a few minutes and catch his breath;
• the answer to the question of whether it is possible to brush your teeth before taking tests is negative: in order to accurately determine blood sugar, in the morning before the study, you need to ignore this hygiene procedure, and also do not drink tea and coffee;
• do not take antibiotics, hormonal drugs, diuretics, etc. before taking blood;
• two weeks before the study, you need to stop taking drugs that affect blood lipids, in particular, statins;
• if you need to take a full analysis again, this must be done at the same time, the laboratory must also be the same.

Deciphering a biochemical blood test

If a clinical blood test was performed, the decoding of the indicators is carried out by a specialist. Also, the interpretation of indicators of a biochemical blood test can be carried out using a special table, which indicates the normal indicators of analyzes in adults and children. If any indicator differs from the norm, it is important to pay attention to this and consult a doctor who can correctly “read” all the results obtained and give his recommendations. If necessary, blood biochemistry is prescribed: an extended profile.

Table for decoding a biochemical blood test in adults

globulins (α1, α2, γ, β)

Thus, a biochemical blood test makes it possible to conduct a detailed analysis to assess the functioning of internal organs. Also, deciphering the results allows you to adequately “read” which vitamins, macro- and microelements, enzymes, hormones the body needs. Blood biochemistry allows you to recognize the presence of metabolic pathologies.

If you correctly decipher the obtained indicators, it is much easier to make any diagnosis. Biochemistry is a more detailed study than the KLA. After all, deciphering the indicators of a general blood test does not allow obtaining such detailed data.

It is very important to conduct such studies during pregnancy. After all, a general analysis during pregnancy does not provide an opportunity to obtain complete information. Therefore, biochemistry in pregnant women is prescribed, as a rule, in the first months and in the third trimester. In the presence of certain pathologies and poor health, this analysis is carried out more often.

In modern laboratories, they are able to conduct a study and decipher the obtained indicators for several hours. The patient is provided with a table in which all the data are indicated. Accordingly, it is even possible to independently track how blood counts are normal in adults and children.

Both the table for deciphering the general blood test in adults and biochemical analyzes are deciphered taking into account the age and gender of the patient. After all, the norm of blood biochemistry, as well as the norm of a clinical blood test, can vary in women and men, in young and elderly patients.

A hemogram is a clinical blood test in adults and children, which allows you to find out the amount of all blood elements, as well as their morphological features, the ratio of leukocytes, hemoglobin content, etc.

Since blood biochemistry is a complex study, it also includes liver tests. Deciphering the analysis allows you to determine whether liver function is normal. Liver parameters are important for diagnosing pathologies of this organ. The following data make it possible to assess the structural and functional state of the liver: ALT, GGTP (GGTP norm in women is slightly lower), alkaline phosphatase enzymes, bilirubin and total protein levels. Liver tests are performed when necessary to establish or confirm the diagnosis.

Cholinesterase is determined to diagnose the severity of intoxication and the state of the liver, as well as its functions.

Blood sugar is determined to assess the functions of the endocrine system. What is the name of the blood test for sugar, you can find out directly in the laboratory. The sugar designation can be found on the results sheet. How is sugar defined? It is denoted by the concept of "glucose" or "GLU" in English.

The CRP rate is important, since a jump in these indicators indicates the development of inflammation. The AST indicator indicates pathological processes associated with tissue destruction.

The MID index in a blood test is determined during a general analysis. The MID level allows you to determine the development of allergies, infectious diseases, anemia, etc. The MID indicator allows you to assess the state of the human immune system.

Lipidogram provides for the determination of indicators of total cholesterol, HDL, LDL, triglycerides. The lipid spectrum is determined in order to identify disorders of lipid metabolism in the body.

The norm of blood electrolytes indicates the normal course of metabolic processes in the body.

Seromucoid is a fraction of blood plasma proteins that includes a group of glycoproteins. Speaking about seromucoid - what it is, it should be noted that if the connective tissue is destroyed, degraded or damaged, seromucoids enter the blood plasma. Therefore, seromucoids are determined to predict the development of tuberculosis.

LDH, LDH (lactate dehydrogenase) is an enzyme involved in the oxidation of glucose and the production of lactic acid.

An analysis for ferritin (a protein complex, the main intracellular depot of iron) is carried out with suspicion of hemochromatosis, chronic inflammatory and infectious diseases, and tumors.

A blood test for ASO is important for diagnosing a variety of complications after a streptococcal infection.

In addition, other indicators are determined, as well as other investigations are carried out (protein electrophoresis, etc.). The norm of a biochemical blood test is displayed in special tables. It displays the norm of a biochemical blood test in women, the table also provides information on normal indicators in men. But still, it is better to ask a specialist who will adequately evaluate the results in the complex and prescribe the appropriate treatment about how to decipher a general blood test and how to read the data of a biochemical analysis.

Decoding of blood biochemistry in children is carried out by a specialist who appointed the study. For this, a table is also used in which the norm for children of all indicators is indicated.

In veterinary medicine, there are also norms for biochemical blood parameters for dogs and cats - the corresponding tables indicate the biochemical composition of animal blood.

What some indicators mean in a blood test is discussed in more detail below.

Total protein of blood serum, fractions of total protein

Protein means a lot in the human body, as it takes part in the creation of new cells, in the transport of substances and the formation of humoral immunity.

The composition of proteins includes 20 basic amino acids, they also contain inorganic substances, vitamins, lipid and carbohydrate residues.

The liquid part of the blood contains approximately 165 proteins, moreover, their structure and role in the body are different. Proteins are divided into three different protein fractions:

Since the production of proteins occurs mainly in the liver, their level indicates its synthetic function.

If the conducted proteinogram indicates that there is a decrease in total protein in the body, this phenomenon is defined as hypoproteinemia. A similar phenomenon occurs in the following cases:

• with protein starvation - if a person follows a certain diet, practices vegetarianism;
• if there is an increased excretion of protein in the urine - with proteinuria, kidney disease, pregnancy;
• if a person loses a lot of blood - with bleeding, heavy periods;
• in case of severe burns;
• with exudative pleurisy, exudative pericarditis, ascites;
• with the development of malignant neoplasms;
• if protein formation is impaired - with cirrhosis, hepatitis;
• with a decrease in the absorption of substances - with pancreatitis, colitis, enteritis, etc .;
• after prolonged use of glucocorticosteroids.

An increased level of protein in the body is hyperproteinemia. There is a difference between absolute and relative hyperproteinemia.

The relative increase in proteins develops in case of loss of the liquid part of the plasma. This happens if you are worried about constant vomiting, with cholera.

An absolute increase in protein is noted if there are inflammatory processes, multiple myeloma.

The concentration of this substance changes by 10% with a change in body position, as well as during physical exertion.

Why do the concentrations of protein fractions change?

Protein fractions - globulins, albumins, fibrinogen.

The standard bioanalysis of blood does not involve the determination of fibrinogen, which reflects the process of blood clotting. Coagulogram - an analysis in which this indicator is determined.

When is the level of protein fractions increased?

• if fluid loss occurs during infectious diseases;
• with burns.

• with purulent inflammation in acute form;
• with burns during the recovery period;
• nephrotic syndrome in patients with glomerulonephritis.

• with viral and bacterial infections;
• with systemic connective tissue diseases (rheumatoid arthritis, dermatomyositis, scleroderma);
• with allergies;
• with burns;
• with helminthic invasion.

When is the level of protein fractions lowered?

• in newborns due to underdevelopment of liver cells;
• with pulmonary edema;
• during pregnancy;
• with liver diseases;
• with bleeding;
• in case of accumulation of plasma in the body cavities;
• with malignant tumors.

The level of nitrogen metabolism

In the body, not only the construction of cells occurs. They also break down, and nitrogenous bases accumulate at the same time. Their formation occurs in the human liver, they are excreted through the kidneys. Therefore, if the indicators of nitrogen metabolism are increased, then a violation of the functions of the liver or kidneys, as well as excessive breakdown of proteins, is likely. The main indicators of nitrogen metabolism are creatinine, urea. Less commonly, ammonia, creatine, residual nitrogen, and uric acid are determined.

Urea

Reasons for the downgrade:

Creatinine

Reasons for the increase:

Uric acid

Reasons for the increase:

• leukemia;
• gout;
• vitamin B-12 deficiency;
• acute infectious diseases;
• Wakez disease;
• liver disease;
• severe diabetes mellitus;
• pathology of the skin;
• carbon monoxide poisoning, barbiturates.

Glucose

Glucose is considered the main indicator of carbohydrate metabolism. It is the main energy product that enters the cell, since the vital activity of the cell depends on oxygen and glucose. After a person has taken food, glucose enters the liver, and there it is utilized in the form of glycogen. These processes are controlled by pancreatic hormones - insulin and glucagon. Due to the lack of glucose in the blood, hypoglycemia develops, its excess indicates that hyperglycemia occurs.

Violation of the concentration of glucose in the blood occurs in the following cases:

hypoglycemia

• with prolonged fasting;
• in case of impaired absorption of carbohydrates - with colitis, enteritis, etc .;
• with hypothyroidism;
• with chronic liver pathologies;
• with insufficiency of the adrenal cortex in a chronic form;
• with hypopituitarism;
• in case of an overdose of insulin or hypoglycemic drugs taken orally;
• with meningitis, encephalitis, insuloma, meningoencephalitis, sarcoidosis.

hyperglycemia

• with diabetes mellitus of the first and second types;
• with thyrotoxicosis;
• in case of development of a pituitary tumor;
• with the development of neoplasms of the adrenal cortex;
• with pheochromocytoma;
• in people who practice treatment with glucocorticoids;
• with epilepsy;
• with injuries and tumors of the brain;
• with psycho-emotional arousal;
• if carbon monoxide poisoning has occurred.

Violation of pigment metabolism in the body

Specific colored proteins are peptides that contain a metal (copper, iron). These are myoglobin, hemoglobin, cytochrome, ceruloplasmin, etc. Bilirubin is the end product of the breakdown of such proteins. When the existence of an erythrocyte in the spleen ends, bilirubin is produced due to biliverdin reductase, which is called indirect or free. This bilirubin is toxic, so it is harmful to the body. However, since it quickly binds to blood albumins, poisoning of the body does not occur.

At the same time, in people who suffer from cirrhosis, hepatitis, there is no connection with glucuronic acid in the body, so the analysis shows a high level of bilirubin. Next, indirect bilirubin binds to glucuronic acid in the liver cells, and it turns into conjugated or direct bilirubin (DBil), which is not toxic. Its high level is noted in Gilbert's syndrome, biliary dyskinesia. If liver tests are performed, transcribing them may show a high level of direct bilirubin if the liver cells are damaged.

Further, together with bile, bilirubin is transported from the hepatic ducts to the gallbladder, then to the duodenum, where urobilinogen is formed. In turn, it is absorbed into the blood from the small intestine, enters the kidneys. As a result, the urine turns yellow. Another part of this substance in the colon is exposed to bacterial enzymes, turns into stercobilin and stains the feces.

Jaundice: why does it occur?

There are three mechanisms for the development of jaundice in the body:

• Too active breakdown of hemoglobin, as well as other pigment proteins. This occurs with hemolytic anemia, snake bites, and also with pathological hyperfunction of the spleen. In this state, the production of bilirubin is very active, so the liver does not have time to process such amounts of bilirubin.
• Liver diseases - cirrhosis, tumors, hepatitis. Pigment formation occurs in normal volumes, but the liver cells affected by the disease are not capable of a normal amount of work.
• Violations of the outflow of bile. This happens in people with cholelithiasis, cholecystitis, acute cholangitis, etc. Due to compression of the biliary tract, the flow of bile into the intestine stops, and it accumulates in the liver. As a result, bilirubin is released back into the blood.

For the body, all these conditions are very dangerous, they must be urgently treated.

Total bilirubin in women and men, as well as its fractions, are examined in the following cases:

Lipid metabolism or cholesterol levels

Lipids are very important for the biological life of the cell. They are involved in the construction of the cell wall, in the production of a number of hormones and bile, vitamin D. Fatty acids are a source of energy for tissues and organs.

Fats in the body fall into three categories:

Lipids in the blood are determined in the form of such compounds:

• chylomicrons (in their composition mainly triglycerides);
• HDL (HDL, high density lipoproteins, "good" cholesterol);
• LDL (VLP, low density lipoproteins, "bad" cholesterol);
• VLDL (very low density lipoproteins).

The designation of cholesterol is present in the general and biochemical blood tests. When a cholesterol test is performed, the decoding includes all indicators, but the most important are indicators of total cholesterol, triglycerides, LDL, HDL.

When donating blood for biochemistry, it should be remembered that if the patient violated the rules for preparing for analysis, if he ate fatty foods, the readings may be incorrect. Therefore, it makes sense to check cholesterol levels again. In this case, you need to consider how to properly take a blood test for cholesterol. To reduce the rates, the doctor will prescribe the appropriate treatment regimen.

Why is lipid metabolism disturbed and what does it lead to?

Total cholesterol rises if:

Total cholesterol is reduced if:

Triglyceride levels increase if:

• alcoholic cirrhosis of the liver;
• viral hepatitis;
• alcoholism;
• biliary cirrhosis of the liver;
• cholelithiasis;
• pancreatitis, acute and chronic;
• renal failure in a chronic form;
• hypertension;
• IHD, myocardial infarction;
• diabetes mellitus, hypothyroidism;
• thrombosis of cerebral vessels;
• pregnancy;
• gout;
• Down syndrome;
• acute intermittent porphyria.

Triglyceride levels decrease if:

• hyperfunction of the glands, thyroid and parathyroid;
• COPD;
• malabsorption of substances;
• malnutrition.

• at 5.2-6.5 mmol / l, there is a mild increase in cholesterol, but there is already a risk of developing atherosclerosis;
• at 6.5-8.0 mmol / l, a moderate increase in cholesterol is recorded, which can be corrected with a diet;
• 8.0 mmol / l and more - high rates at which treatment is necessary, its scheme to lower cholesterol levels is determined by the doctor.

Depending on how the lipid metabolism indicators change, five degrees of dyslipoproteinemia are determined. This condition is a harbinger of the development of serious diseases (atherosclerosis, diabetes, etc.).

Blood enzymes

Each biochemical laboratory also determines enzymes, special proteins that speed up chemical reactions in the body.

Main blood enzymes:

• aspartate aminotransferase (AST, AST);
• alanine aminotransferase (ALT, ALT);
• gamma-glutamyltransferase (GGT, LDL);
• alkaline phosphatase (AP);
• creatine kinase (CK);
• alpha amylase.

The listed substances are contained inside different organs, there are very few of them in the blood. Enzymes in the blood are measured in units / l (international units).

Aspartate aminotransferase (ACAT) and alanine aminotransferase

Enzymes responsible in chemical reactions for the transfer of aspartate and alanine. A large amount of ALT and AST is found in the tissues of the heart, liver, and skeletal muscles. If there is an increase in AST and ALT in the blood, this indicates that the cells of the organs are being destroyed. Accordingly, the higher the level of these enzymes is in the human blood, the more cells died, which means that an organ is destroyed. How to lower ALT and AST depends on the diagnosis and doctor's prescription.

Three degrees of increase in enzymes are determined:

• 1.5-5 times - light;
• 6-10 times - average;
• 10 times or more is high.

What diseases lead to an increase in AST and ALT?

• myocardial infarction (more ALT is noted);
• acute viral hepatitis (more AST is noted);
• malignant tumors and liver metastasis;
• toxic damage to liver cells;
• crash syndrome.

Alkaline phosphatase (ALP)

This enzyme determines the cleavage of phosphoric acid from chemical compounds, as well as the delivery of phosphorus inside the cells. The bone and hepatic forms of alkaline phosphatase are determined.

The level of the enzyme increases with such diseases:

• myeloma;
• osteogenic sarcoma;
• lymphogranulomatosis;
• hepatitis;
• bone metastasis;
• drug and toxic liver damage;
• fracture healing process;
• osteomalacia, osteoporosis;
• cytomegalovirus infection.

Gammaglutamyl transferase (GGT, glutamyl transpeptidase)

It should be taken into account when discussing GGT that this substance is involved in the metabolic process of fats, transfers triglycerides and cholesterol. The largest amount of this enzyme is found in the kidneys, prostate, liver, pancreas.

If GGT is elevated, the causes are most often related to liver disease. The enzyme gamma-glutamine transferase (GGT) is also elevated in diabetes mellitus. Also, the enzyme gamma-glutamyl transferase is increased in infectious mononucleosis, alcohol intoxication, and in patients with heart failure. More information about GGT - what it is, will be told by a specialist who deciphers the results of the tests. If GGTP is elevated, the causes of this phenomenon can be determined by conducting additional studies.

Creatine kinase (creatine phosphokinase)

It should be taken into account, when evaluating blood CPK, that this is an enzyme, high concentrations of which are observed in skeletal muscles, in the myocardium, a smaller amount of it is in the brain. If there is an increase in the enzyme creatine phosphokinase, the reasons for the increase are associated with certain diseases.

This enzyme is involved in the conversion of creatine, and also ensures the maintenance of energy metabolism in the cell. Three subtypes of QC are defined:

If creatine kinase is elevated in the blood, the reasons for this are usually associated with the destruction of the cells of the organs listed above. If creatine kinase in the blood is elevated, the reasons may be as follows:

MM Creatine Kinase

• myositis;
• prolonged squeezing syndrome;
• myasthenia gravis;
• gangrene;
• amyotrophic lateral sclerosis;
• Guillain-Barré syndrome.

MB Creatine Kinase

• acute myocardial infarction;
• hypothyroidism;
• myocarditis;
• long-term use of prednisone.

BB Creatine Kinase

• encephalitis;
• long-term treatment of schizophrenia.

Alpha amylase

The function of amylase is the breakdown of complex carbohydrates into simple ones. Amylase (diastase) is found in the salivary and pancreas. When tests are deciphered online or by a doctor, attention is paid to both increasing and decreasing this indicator.

Alpha-amylase increases if:

• acute pancreatitis;
• pancreas cancer;
• parotitis;
• viral hepatitis;
• acute renal failure;
• prolonged use of alcohol, as well as glucocorticosteroids, tetracycline.

Alpha-amylase is reduced if:

Blood electrolytes - what is it?

Sodium and potassium are the main electrolytes in human blood. Without them, not a single chemical process can do in the body. Blood ionogram - an analysis during which a complex of microelements in the blood is determined - potassium, calcium, magnesium, sodium, chlorides, etc.

Potassium

It is very necessary for metabolic and enzymatic processes.

Its main function is to conduct electrical impulses in the heart. Therefore, if the norm of this element in the body is violated, this means that a person may experience impaired myocardial function. Hyperkalemia is a condition in which potassium levels are elevated and hypokalemia is reduced.

If potassium is elevated in the blood, the specialist must find the causes and eliminate them. After all, such a condition can threaten the development of conditions dangerous for the body:

Such conditions are possible if the potassium rate is increased to 7.15 mmol / l or more. Therefore, potassium in women and men must be periodically monitored.

If a bio-blood test gives results of a potassium level of less than 3.05 mmol / l, such parameters are also dangerous for the body. In this condition, the following symptoms are noted:

• nausea and vomiting;
• labored breathing;
• muscle weakness;
• heart weakness;
• involuntary excretion of urine and feces.

Sodium

It is also important how much sodium is in the body, despite the fact that this element is not directly involved in metabolism. Sodium is present in the extracellular fluid. It maintains osmotic pressure and pH levels.

Sodium is excreted in the urine, and this process is controlled by aldosterone, a hormone of the adrenal cortex.

Hypernatremia, that is, an increased level of sodium, leads to a feeling of thirst, irritability, muscle tremors and twitches, seizures and coma.

Rheumatic tests

Rheumoprobes - a comprehensive immunochemical blood test, which includes a study to determine the rheumatoid factor, an analysis of circulating immune complexes, and the determination of antibodies to o-streptolysin. Rheumoprobes can be carried out independently, as well as as part of the research that provides for immunochemistry. Rheumoprobes should be performed if there are complaints of pain in the joints.

conclusions

Thus, a general therapeutic detailed biochemical blood test is a very important study in the diagnostic process. For those who want to conduct a complete extended BH blood test or UAC in a polyclinic or in a laboratory, it is important to consider that a certain set of reagents, analyzers and other devices are used in each laboratory. Consequently, the norms of indicators may differ, which must be taken into account when studying what a clinical blood test or biochemistry results show. Before reading the results, it is important to make sure that the standards are indicated on the form that is issued in the medical institution in order to decipher the test results correctly. The norm of KLA in children is also indicated in the forms, but the doctor should evaluate the results.

Many are interested in: a blood test form 50 - what is it and why take it? This is an analysis to determine the antibodies that are in the body if it is infected with HIV. F50 analysis is done both for suspected HIV and for the purpose of prevention in a healthy person. It is also worth preparing properly for such a study.

Can mean: same as tag; Tagos or tag (other Greek ταγός, "leader, leader") the supreme leader of ancient Thessaly. Tages or Tag Etruscan god or hero; Tag or Thing, a popular assembly of the ancient Germans; Tag (Hebrew) signs used ... ... Wikipedia

TAG- (Tagetus), in Etruscan mythology, a child miraculously found in the ground near the city of Tarquinius, who taught the Etruscans to predict the future. Among the Latins, Tagus was considered the "underground" Hercules, the son of Genius and the grandson of Jupiter. Tag's teaching also spoke of... encyclopedic Dictionary

TAG- in Etruscan mythology, a child miraculously found in the ground near the city of Tarquinius, who taught the Etruscans to predict the future ... Big Encyclopedic Dictionary

TAG- in Etruscan mythology, a child who possessed the wisdom of a prophet and experienced in the art of divination. He was plowed out of the ground in the vicinity of the city of Tarquinius and died after he predicted the future of the Etruscans and taught them his science. The name T. was produced from ... ... Encyclopedia of mythology

tag- noun, number of synonyms: 2 descriptor (5) tag (3) ASIS synonym dictionary. V.N. Trishin. 2013 ... Synonym dictionary

Tagil- the name of a human family river in Siberia ... Spelling Dictionary of Ukrainian Movies

tag- I [تگ] 1. zer, buni har chiz: tagi bom, tagi deg, tagi choh, tagi darakht 2. pesh, back; tagi gap (khabar, kor) mohiyat va asli matlab; az tagi dil az sidqi dil, az zamiri dil; az tagi chashm nigoh kardani pinhoni, duzdida nigaristan; kurtai tag… …

tagoy- [تگ جاي] muqim², doim², taҳҷo²; agholii tagҷoii mardumi makhalli, muқimі va doimі dar ҷoe, bumі, taҳҷoii ... Farhangi tafsiria zaboni tojiki

TAG, (I)- Tages, son of Jupiter's Genius (Genius Iovialis), grandson of Jupiter, who taught the Etruscans the art of divination. The myth says that when a plowman was plowing the ground near the city of Tarquinius, T. suddenly jumped out of the furrow, a boy in appearance, an old man in mind. ... ...

TAG, (II)- Tagus, Ταγός, n. Tejo or Tagus, a significant river in Spain, whose sources were in the land of the Celtiberians between the mountains of Orospeda and Idubeda. According to the testimony of the ancients, it abounded with golden sand, from which now ... ... Real Dictionary of Classical Antiquities

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Formation of glycerol-3-phosphate

At the beginning of the whole process, the formation of glycerol-3-phosphate occurs.

Glycerol in liver is activated in the phosphorylation reaction using ATP macroergic phosphate. IN muscles, adipose tissue and others this reaction absent, therefore, in them, glycerol-3-phosphate is formed from dihydroxyacetone phosphate, a metabolite of glycolysis.

Synthesis of phosphatidic acid

Fatty acids coming from the blood during the breakdown of HyloMicrons, VLDL or synthesized in the cell de novo from glucose should also be activated. They are converted to acyl-S-CoA in an ATP-dependent reaction.

fatty acid activation reaction

In the presence of glycerol-3-phosphate and acyl-S-CoA, phosphatidic acid is synthesized.

The reaction for the synthesis of phosphatidic acid

Depending on the type of fatty acid, the resulting phosphatidic acid may contain saturated or unsaturated fatty acids. Simplifying the situation somewhat, it can be noted that the fatty acid composition of phosphatidic acid determines its further fate:

• if saturated and monounsaturated acids (palmitic, stearic, palmitoleic, oleic) are used, then phosphatidic acid is directed to the synthesis of TAG,
• when polyunsaturated fatty acids (linolenic, arachidonic, ω3-series acids) are included, phosphatidic acid is a precursor of phospholipids.

Synthesis of triacylglycerols

The synthesis of TAG consists in the dephosphorylation of phosphatidic acid and the addition of an acyl group. This process increases when at least one of the following conditions is met:

• availability of a source of "cheap" energy. For example,
  1) a diet rich in simple carbohydrates (glucose, sucrose) - while the concentration of glucose in the blood after a meal rises sharply and, under the influence of insulin, fat synthesis actively occurs in adipocytes and liver.
  2) availability ethanol, high-energy compound, assuming a normal diet - an example is "beer obesity". Fat synthesis is active here in liver.
• P increased levels of fatty acids in the blood, for example, with increased lipolysis in fat cells under the influence of any substances (pharmaceuticals, caffeine, etc.), with emotional stress and lack of (!) muscle activity. Synthesis of TAG occurs in the liver,
• high concentrations insulin and low concentrations glucagon- after a meal.

Reactions for the synthesis of TAG from phosphatidic acid

After TAG synthesis, they are evacuated from the liver to other tissues, more precisely, to tissues that have lipoprotein lipase on the endothelium of their capillaries.

The transport form is VLDL. Strictly speaking, the cells of the body need only fatty acids, all other components of VLDL are not necessary.

Abbreviations

TAG - triacylglycerols

PL - phospholipids C - cholesterol

cxc - free cholesterol

eCS - esterified cholesterol PS - phosphatidylserine

PC - phosphatidylcholine

PEA - phosphatidylethanolamine FI - phosphatidylinositol

MAG - monoacylglycerol

DAG - diacylglycerol PUFA - polyunsaturated fatty acids

fatty acids

XM - chylomicrons LDL - low density lipoproteins

VLDL - very low density lipoproteins

HDL - high density lipoproteins

LIPID CLASSIFICATION

The possibility of classifying lipids is difficult, since the class of lipids includes substances that are very diverse in structure. They are united by only one property - hydrophobicity.

STRUCTURE OF INDIVIDUAL REPRESENTATIVES OF LI-PIDS

Fatty acid

Fatty acids are part of almost all of these classes of lipids,

except for derivatives of CS.

Human fat fatty acids are characterized by the following features:

an even number of carbon atoms in the chain,

no chain branching

the presence of double bonds only in cis-conformations

in turn, the fatty acids themselves are heterogeneous and differ long

chain and quantity double bonds.

TO rich fatty acids include palmitic (C16), stearic

(C18) and arachidic (C20).

TO monounsaturated- palmitoleic (С16:1), oleic (С18:1). These fatty acids are found in most dietary fats.

Polyunsaturated fatty acids contain 2 or more double bonds,

separated by a methylene group. In addition to differences in quantity double bonds, acids differ in their position relative to the beginning of the chain (denoted by

cut the Greek letter "delta") or the last carbon atom of the chain (denoted

letter ω "omega").

According to the position of the double bond relative to the last carbon atom, the polyline

saturated fatty acids are divided into

ω-6-fatty acids - linoleic (C18:2, 9.12), γ-linolenic (C18:3, 6,9,12),

arachidonic (С20:4, 5,8,11,14). These acids form vitamin F, and co-

held in vegetable oils.

ω-3-fatty acids - α-linolenic (C18: 3, 9,12,15), timnodonic (eicoso-

pentaenoic, C20;5, 5,8,11,14,17), klupanodone (docosapentaenoic, C22:5,

7,10,13,16,19), cervonic (docosahexaenoic, C22:6, 4,7,10,13,16,19). Nai-

a more significant source of acids of this group is the fat of cold fish

seas. An exception is α-linolenic acid, found in hemp.

nom, linseed, corn oils.

Role of fatty acids

It is with fatty acids that the most famous function of lipids is associated - energy

getic. Thanks to the oxidation of fatty acids, body tissues receive more

half of all energy (see β-oxidation), only erythrocytes and nerve cells do not use them in this capacity.

Another and very important function of fatty acids is that they are a substrate for the synthesis of eicosanoids - biologically active substances that change the amount of cAMP and cGMP in the cell, modulating the metabolism and activity of both the cell itself and surrounding cells. . Otherwise, these substances are called local or tissue hormones.

Eicosanoids include oxidized derivatives of eicosotrienoic (C20:3), arachidonic (C20:4), timnodonic (C20:5) fatty acids. They cannot be deposited, they are destroyed within a few seconds, and therefore the cell must constantly synthesize them from incoming polyene fatty acids. There are three main groups of eicosanoids: prostaglandins, leukotrienes, thromboxanes.

Prostaglandins (Pg) - are synthesized in almost all cells, except for erythrocytes and lymphocytes. There are types of prostaglandins A, B, C, D, E, F. Functions prostaglandins are reduced to a change in the tone of the smooth muscles of the bronchi, genitourinary and vascular systems, gastrointestinal tract, while the direction of changes is different depending on the type of prostaglandins and conditions. They also affect body temperature.

Prostacyclins are a subtype of prostaglandins (PgI) , but additionally have a special function - they inhibit platelet aggregation and cause vasodilation. Synthesized in the endothelium of the vessels of the myocardium, uterus, gastric mucosa.

Thromboxanes (Tx) formed in platelets, stimulate their aggregation and

called vasoconstriction.

Leukotrienes (Lt) synthesized in leukocytes, in the cells of the lungs, spleen, brain

ha, hearts. There are 6 types of leukotrienes A, B, C, D, E, F. In leukocytes, they

stimulate cell motility, chemotaxis, and cell migration to the focus of inflammation; in general, they activate inflammation reactions, preventing its chronicity. Cause co-

contraction of the muscles of the bronchi in doses 100-1000 times less than histamine.

Addition

Depending on the initial fatty acid, all eicosanoids are divided into three groups:

First group – formed from linoleic acid in accordance with the number of double bonds, prostaglandins and thromboxanes are assigned an index

1, leukotrienes - index 3: for example,Pg E1, Pg I1, Tx A1, Lt A3.

It's interesting thatPGE1 inhibits adenylate cyclase in adipose tissue and prevents lipolysis.

Second group synthesized from arachidonic acid according to the same rule, it is assigned an index of 2 or 4: for example,Pg E2, Pg I2, Tx A2, Lt A4.

Third group eicosanoids are derived from thymnodonic acid, by number

double bonds are assigned indices 3 or 5: for example,Pg E3, Pg I3, Tx A3, Lt A5

The subdivision of eicosanoids into groups is of clinical importance. This is especially pronounced in the example of prostacyclins and thromboxanes:

	Initial	Number	Activity	Activity
	oily	double bonds
			prostacyclins	thromboxanes
	acid	in a molecule
	γ - Linolenova
	i C18:3,
	Arachidonic
	Timnodono-		increase	descending
			activity	activity

The resulting effect of the use of more unsaturated fatty acids is the formation of thromboxanes and prostacyclins with a large number of double bonds, which shifts the rheological properties of the blood to a decrease in viscosity.

bones, lowering thrombosis, dilates blood vessels and improves blood

tissue supply.

1. Researchers' attention to ω -3 acids attracted the phenomenon of the Eskimos, co-

indigenous inhabitants of Greenland and the peoples of the Russian Arctic. Against the background of a high consumption of animal protein and fat and a very small amount of vegetable products, they had a number of positive features:

no incidence of atherosclerosis, ischemic disease

heart and myocardial infarction, stroke, hypertension;

increased content of HDL in blood plasma, a decrease in the concentration of total cholesterol and LDL;

reduced platelet aggregation, low blood viscosity

a different fatty acid composition of cell membranes compared to the European

mi - S20:5 was 4 times more, S22:6 16 times!

This state is calledANTIATHEROSCLEROSIS .

2. Besides, in experiments to study the pathogenesis of diabetes mellitus it was found that prior applicationω -3 fatty acids pre-

prevented death in experimental ratsβ -cells of the pancreas when using alloxan (alloxan diabetes).

Indications for useω -3 fatty acids:

prevention and treatment of thrombosis and atherosclerosis,

diabetic retinopathy,

dyslipoproteinemia, hypercholesterolemia, hypertriacylglycerolemia,

myocardial arrhythmias (improvement in conduction and rhythm),

peripheral circulatory disorders

Triacylglycerols

Triacylglycerols (TAGs) are the most abundant lipids in

human body. On average, their share is 16-23% of the body weight of an adult. TAG functions are:

reserve energy, the average person has enough fat reserves to support

life activity during 40 days of complete starvation;

heat-saving;

mechanical protection.

Addition

An illustration of the function of triacylglycerols are the care requirements

premature babies who have not yet had time to develop a fatty layer - they need to be fed more often, take additional measures against hypothermia of the baby

The composition of TAG includes the trihydric alcohol glycerol and three fatty acids. Fat-

nye acids can be saturated (palmitic, stearic) and monounsaturated (palmitoleic, oleic).

Addition

An indicator of the unsaturation of fatty acid residues in TAG is the iodine number. For a person, it is 64, for creamy margarine 63, for hemp oil - 150.

By structure, simple and complex TAGs can be distinguished. In simple TAGs, everything is fat-

nye acids are the same, for example, tripalmitate, tristearate. In complex TAGs, fat-

nye acids are different, : dipalmitoyl stearate, palmitoyl oleyl stearate.

Rancidity of fats

Rancidity of fats is a household term for lipid peroxidation, which is widespread in nature.

Lipid peroxidation is a chain reaction in which

the formation of one free radical stimulates the formation of other free radicals

ny radicals. As a result, polyene fatty acids (R) form their hydroperoxides(ROOH). Antioxidant systems counteract this in the body.

we, including vitamins E, A, C and enzymes catalase, peroxidase, superoxide

dismutase.

Phospholipids

Phosphatic acid (PA)- intermediate co-

unity for the synthesis of TAG and PL.

Phosphatidylserine (PS), phosphatidylethanolamine (PEA, cephalin), phosphatidylcholine (PC, lecithin)–

structural PL, together with cholesterol form a lipid

bilayer of cell membranes, regulate the activity of membrane enzymes and membrane permeability.

Besides, dipalmitoylphosphatidylcholine, being

surfactant, serves as the main component surfactant

lung alveoli. Its deficiency in the lungs of preterm infants leads to the development of syn-

droma of respiratory failure. Another function of FH is its participation in education. bile and maintaining the cholesterol in it in a dissolved

Phosphatidylinositol (FI) plays a key role in phospholipid-calcium

mechanism of hormonal signal transduction into the cell.

Lysophospholipids is a product of hydrolysis of phospholipids by phospholipase A2.

Cardiolipin a structural phospholipid in the mitochondrial membrane Plasmalogens-participate in the construction of the structure of membranes, up to

10% phospholipids of the brain and muscle tissue.

Sphingomyelins Most of them are located in the nervous tissue.

EXTERNAL LIPIDS METABOLISM.

The lipid requirement of an adult organism is 80-100 g per day, of which

vegetable (liquid) fats should be at least 30%.

Triacylglycerols, phospholipids and cholesterol esters come with food.

Oral cavity.

It is generally accepted that lipids are not digested in the mouth. However, there is evidence of infant secretion of tongue lipase by Ebner's glands. Lingual lipase secretion is stimulated by sucking and swallowing movements during breastfeeding. This lipase has an optimum pH of 4.0-4.5, which is close to the pH of the gastric contents of infants. It is most active against milk TAGs with short and medium fatty acids and ensures the digestion of about 30% of emulsified milk TAGs to 1,2-DAG and free fatty acid.

Stomach

Own lipase of the stomach in an adult does not play a significant role in the

lipid digestion due to its low concentration, the fact that its optimum pH is 5.5-7.5,

lack of emulsified fats in food. In infants, gastric lipase is more active, since in the stomach of children the pH is about 5 and milk fats are emulsified.

Additionally, fats are digested due to the lipase contained in milk ma-

teri. Lipase is absent in cow's milk.

However, the warm environment, gastric peristalsis causes emulsification of fats, and even low active lipase breaks down small amounts of fat,

which is important for the further digestion of fats in the intestines. The presence of a mini-

a small amount of free fatty acids stimulates the secretion of pancreatic lipase and facilitates the emulsification of fats in the duodenum.

Intestines

Digestion in the intestine is carried out under the influence of pancreatic

lipases with an optimum pH of 8.0-9.0. It enters the intestine in the form of prolipase, pre-

rotating into an active form with the participation of bile acids and colipase. Colipase, a trypsin-activated protein, forms a complex with lipase in a 1:1 ratio.

acting on emulsified food fats. As a result,

2-monoacylglycerols, fatty acids and glycerol. Approximately 3/4 TAG after hydro-

lysis remain in the form of 2-MAG and only 1/4 of the TAG is completely hydrolyzed. 2-

MAGs are absorbed or converted by monoglyceride isomerase to 1-MAG. The latter is hydrolyzed to glycerol and fatty acids.

Up to 7 years, the activity of pancreatic lipase is low and reaches a maximum by

pancreatic juice also has an active

trypsin-induced phospholipase A2 has been found

phospholipase C and lysophospholipase activity. The resulting lysophospholipids are ho-

roshim surfactant, so

mu they contribute to the emulsification of dietary fats and the formation of micelles.

intestinal juice has phospho-

lipases A2 and C.

Phospholipases require Ca2+ ions to help remove

fatty acids from the catalysis zone.

Hydrolysis of cholesterol esters is carried out by cholesterol-esterase of pancreatic juice.

Bile

Compound

Bile is alkaline. It produces a dry residue - about 3% and water -97%. In the dry residue, two groups of substances are found:

sodium, potassium, creatinine, cholesterol, phosphatidylcholine that got here by filtering from the blood

bilirubin, bile acids actively secreted by hepatocytes.

Normally, there is a ratio bile acids : FH : XC equal 65:12:5 .

about 10 ml of bile per kg of body weight is formed per day, thus, in an adult it is 500-700 ml. Bile formation is continuous, although the intensity fluctuates sharply throughout the day.

The role of bile

Along with pancreatic juice neutralization sour chyme, I act

scoop from the stomach. At the same time, carbonates interact with HCl, carbon dioxide is released and the chyme is loosened, which facilitates digestion.

Provides fat digestion

emulsification for subsequent exposure to lipase, a combination is necessary

nation [bile acids, unsaturated acids and MAGs];

reduces surface tension, which prevents the droplets of fat from draining;

the formation of micelles and liposomes that can be absorbed.

Thanks to paragraphs 1 and 2, it ensures the absorption of fat-soluble vitamins.

Excretion excess cholesterol, bile pigments, creatinine, metals Zn, Cu, Hg,

medicines. For cholesterol, bile is the only route of excretion, 1-2 g / day is excreted.

Bile acid formation

The synthesis of bile acids occurs in the endoplasmic reticulum with the participation of cytochrome P450, oxygen, NADPH and ascorbic acid. 75% cholesterol formed in

The liver is involved in the synthesis of bile acids. Under experimental hypovitami-

nose C guinea pigs have developed except for scurvy atherosclerosis and gallstone disease. This is due to the retention of cholesterol in cells and a violation of its dissolution in

bile. Bile acids (cholic, deoxycholic, chenodeoxycholic) are synthesized

are in the form of paired compounds with glycine - glyco derivatives and with taurine - tauro derivatives, in a ratio of 3: 1, respectively.

enterohepatic circulation

This is the continuous secretion of bile acids into the intestinal lumen and their reabsorption in the ileum. There are 6-10 such cycles per day. Thus,

a small amount of bile acids (only 3-5 g) ensures digestion

lipids received during the day.

Violation of bile formation

Violation of bile formation is most often associated with a chronic excess of cholesterol in the body, since bile is the only way to remove it. As a result of a violation of the ratio between bile acids, phosphatidylcholine and cholesterol, a supersaturated solution of cholesterol is formed from which the latter precipitates in the form gallstones. In addition to the absolute excess of cholesterol in the development of the disease, the lack of phospholipids or bile acids plays a role in the violation of their synthesis. Stagnation in the gallbladder, which occurs with malnutrition, leads to thickening of bile due to the reabsorption of water through the wall, lack of water in the body also exacerbates this problem.

It is believed that 1/3 of the world's population has gallstones, by old age these values ​​reach 1/2.

Interesting data on the ability of ultrasound to detect

gallstones in only 30% of cases.

Treatment

Chenodeoxycholic acid at a dose of 1 g / day. Causes a decrease in cholesterol deposition

dissolution of cholesterol stones. Pea-sized stones without bilirubin layers

ny dissolve within six months.

Inhibition of HMG-S-CoA reductase (lovastatin) - reduces synthesis by 2 times

Adsorption of cholesterol in the gastrointestinal tract (cholestyramine resins,

Questran) and preventing its absorption.

Suppression of the function of enterocytes (neomycin) - a decrease in the absorption of fats.

Surgical removal of the ileum and termination of reabsorption

bile acids.

lipid absorption.

Occurs in the upper small intestine in the first 100 cm.

short fatty acids absorbed without any additional mechanisms, directly.

Other components form micelles with hydrophilic and hydrophobic

layers. The size of micelles is 100 times smaller than the smallest emulsified fat droplets. Through the aqueous phase, micelles migrate to the brush border of the mucosa.

shells.

Regarding the mechanism of lipid absorption itself, there is no well-established idea. First point vision lies in the fact that micelles penetrate inside

whole cells by diffusion without energy expenditure. Cells break down

micelles and the release of bile acids into the blood, FA and MAG remain and form TAG. By another point vision, micelles are taken up by pinocytosis.

And finally Thirdly, it is possible to penetrate into the cell only lipid com-

components, and bile acids are absorbed in the ileum. Normally, 98% of dietary lipids are absorbed.

Digestion and absorption disorders may occur

in diseases of the liver and gallbladder, pancreas, intestinal wall,

damage to enterocytes with antibiotics (neomycin, chlortetracycline);

excess calcium and magnesium in water and food, which form bile salts, interfering with their function.

Lipid resynthesis

This is the synthesis of lipids in the intestinal wall from post-

exogenous fats sold here, endogenous fatty acids can also be partially used.

When synthesizing triacylglycerols received

fatty acid is activated through the addition of co-

enzyme A. The resulting acyl-S-CoA is involved in the synthesis of triacylglycemic

reads in two possible ways.

First way–2-monoacylglyceride, occurs with the participation of exogenous 2-MAH and FA in the smooth endoplasmic reticulum: a multienzyme complex

triglyceride synthase forms TAG

In the absence of 2-MAG and a high content of fatty acids, second way,

glycerol phosphate mechanism in the rough endoplasmic reticulum. The source of glycerol-3-phosphate is the oxidation of glucose, since dietary glycerol

roll quickly leaves the enterocytes and goes into the blood.

Cholesterol is esterified using acylS- CoA and AChAT enzyme. Reesterification of cholesterol directly affects its absorption into the blood. At present, possibilities are being sought to suppress this reaction in order to reduce the concentration of cholesterol in the blood.

Phospholipids are resynthesized in two ways - using 1,2-MAH for the synthesis of phosphatidylcholine or phosphatidylethanolamine, or through phosphatidic acid in the synthesis of phosphatidylinositol.

Lipid transport

Lipids are transported in the aqueous phase of the blood as part of special particles - li-poproteins.The surface of the particles is hydrophilic and is formed by proteins, phospho-lipids and free cholesterol. Triacylglycerols and cholesterol esters make up the hydrophobic core.

The proteins in lipoproteins are commonly referred to as apoproteins, several of their types are distinguished - A, B, C, D, E. In each class of lipoproteins there are corresponding apoproteins that perform structural, enzymatic and cofactor functions.

Lipoproteins differ in the ratio

niyu triacylglycerols, cholesterol and its

esters, phospholipids and as a class of complex proteins consist of four classes.

chylomicrons (XM);

very low density lipoproteins (VLDL, pre-β-lipoproteins, pre-β-LP);

low density lipoproteins (LDL, β-lipoproteins, β-LP);

high density lipoproteins (HDL, α-lipoproteins, α-LP).

Transport of triacylglycerols

Transport of TAGs from the intestines to tissues is carried out in the form of chylomicrons, from the liver to tissues - in the form of very low density lipoproteins.

Chylomicrons

general characteristics

formed in intestines from resynthesized fats

they contain 2% protein, 87% TAG, 2% cholesterol, 5% cholesterol esters, 4% phospholipids. Os-

the new apoprotein is apoB-48.

are normally not detected on an empty stomach, appear in the blood after a meal,

coming from the lymph through the thoracic lymphatic duct, and completely disappeared

yut after 10-12 hours.

not atherogenic

Function

Transport of exogenous TAGs from the intestine to tissues that store and use

stinging fats, mainly world

tissue, lungs, liver, myocardium, lactating mammary gland, bone

brain, kidney, spleen, macrophages

Disposal

On the endothelium of the capillaries above

listed tissues is fer-

cop lipoprotein lipase, attach-

attached to the membrane by glycosaminoglycans. It hydrolyzes TAG, which are part of chylomicrons to free

fatty acids and glycerol. Fatty acids move into the cells, or remain in the blood plasma and, in combination with albumin, are carried with the blood to other tissues. Lipoprotein lipase is able to remove up to 90% of all TAGs located in the chylomicron or VLDL. After finishing her work residual chylomicrons fall into

liver and are destroyed.

Very low density lipoproteins

general characteristics

synthesized in liver from endogenous and exogenous lipids

8% protein, 60% TAG, 6% cholesterol, 12% cholesterol esters, 14% phospholipids The main protein is apoB-100.

normal concentration is 1.3-2.0 g/l

slightly atherogenic

Function

Transport of endogenous and exogenous TAGs from the liver to tissues that store and use

using fats.

Disposal

Similar to the situation with chylomicrons, in tissues they are exposed to

lipoprotein lipase, after which the residual VLDL is either evacuated to the liver or converted into another type of lipoprotein - low-

which density (LDL).

MOBILIZATION OF FAT

IN resting state liver, heart, skeletal muscle and other tissues (except

erythrocytes and nervous tissue) more than 50% of energy is obtained from the oxidation of fatty acids coming from adipose tissue due to background TAG lipolysis.

Hormone dependent activation of lipolysis

At tension organism (starvation, prolonged muscular work, cooling

ing) hormone-dependent activation of TAG lipase occurs adipocytes. Except

TAG-lipases, in adipocytes there are also DAG- and MAG-lipases, the activity of which is high and constant, but at rest it is not manifested due to the lack of substrates.

As a result of lipolysis, free glycerol And fatty acid. Glycerol transported in the blood to the liver and kidneys here is phosphorylated and converted to the glycolysis metabolite glyceraldehyde phosphate. Depending on the us-

lovium GAF can be involved in gluconeogenesis reactions (during starvation, muscle exercise) or oxidized to pyruvic acid.

Fatty acid transported in complex with plasma albumin

during physical exertion - in the muscles

during starvation - in most tissues and about 30% are captured by the liver.

During fasting and physical exertion after penetration into the cells, fatty acids

slots enter the β-oxidation pathway.

β - fatty acid oxidation

β-oxidation reactions occur

mitochondria in most cells of the body. For oxidation use

fatty acids coming

cytosol from the blood or with intracellular lipolysis of TAG.

Before penetrating into the mat-

mitochondrial rix and be oxidized, the fatty acid must activate-

Xia.This is done by attaching

with coenzyme A.

Acyl-S-CoA is a high-energy

genetic connection. Irreversible

the reaction is achieved by hydrolysis of diphosphate into two molecules

phosphoric acid

Acyl-S-CoA synthetases are located

in the endoplasmic reticulum

IU, on the outer membrane of mitochondria and inside them. There are a number of synthetases specific to different fatty acids.

Acyl-S-CoA is not capable of passing

blow through the mitochondrial membrane

brane, so there is a way to transfer it in combination with vitamins

like substance carnity-

nom.There is an enzyme on the outer membrane of mitochondria carnitine-

acyl transferaseI.

After binding to carnitine, the fatty acid is transported through

translocase membrane. Here, on the inside of the membrane, fer-

cop carnitine acyl transferase II

re-forms acyl-S-CoA which

enters the path of β-oxidation.

The process of β-oxidation consists of 4 reactions, repeated cyclically

Czech. They successively

there is oxidation of the 3rd carbon atom (β-position) and as a result from fat-

acid, acetyl-S-CoA is cleaved off. The remaining shortened fatty acid returns to the first

reactions and everything repeats again, until

until two acetyl-S-CoA are formed in the last cycle.

Oxidation of unsaturated fatty acids

When unsaturated fatty acids are oxidized, the cell needs

additional enzyme isomerases. These isomerases move double bonds in fatty acid residues from γ- to β-position, transfer natural double bonds

connections from cis- V trance-position.

Thus, the already existing double bond is prepared for β-oxidation and the first reaction of the cycle, in which FAD is involved, is skipped.

Oxidation of fatty acids with an odd number of carbon atoms

Fatty acids with an odd number of carbons enter the body with plants.

body food and seafood. Their oxidation occurs in the usual way to

the last reaction in which propionyl-S-CoA is formed. The essence of the transformations of propionyl-S-CoA is reduced to its carboxylation, isomerization and formation

succinyl-S-CoA. Biotin and vitamin B 12 are involved in these reactions.

Energy balance β -oxidation.

When calculating the amount of ATP formed during β-oxidation of fatty acids, it is necessary

take into account

number of β-oxidation cycles. The number of β-oxidation cycles can be easily represented based on the idea of ​​a fatty acid as a chain of two-carbon units. The number of breaks between units corresponds to the number of β-oxidation cycles. The same value can be calculated using the formula n / 2 -1, where n is the number of carbon atoms in the acid.

the amount of acetyl-S-CoA formed is determined by the usual division of the number of carbon atoms in the acid by 2.

the presence of double bonds in fatty acids. In the first reaction of β-oxidation, the formation of a double bond occurs with the participation of FAD. If there is already a double bond in the fatty acid, then this reaction is not necessary and FADH2 is not formed. The remaining reactions of the cycle go without changes.

the amount of energy used to activate

Example 1 Oxidation of palmitic acid (C16).

For palmitic acid, the number of β-oxidation cycles is 7. In each cycle, 1 FADH2 molecule and 1 NADH molecule are formed. Entering the respiratory chain, they will "give" 5 ATP molecules. In 7 cycles, 35 ATP molecules are formed.

Since there are 16 carbon atoms, 8 molecules of acetyl-S-CoA are formed during β-oxidation. The latter enters the TCA, when it is oxidized in one turn of the cycle

la formed 3 molecules of NADH, 1 molecule of FADH2 and 1 molecule of GTP, which is equivalent to

Lente 12 ATP molecules. Only 8 molecules of acetyl-S-CoA will provide the formation of 96 ATP molecules.

There are no double bonds in palmitic acid.

1 molecule of ATP goes to activate the fatty acid, which, however, is hydrolyzed to AMP, that is, 2 macroergic bonds are spent.

Thus, summing up, we get 96 + 35-2 = 129 ATP molecules.

Example 2 Oxidation of linoleic acid.

The number of acetyl-S-CoA molecules is 9. So 9×12=108 ATP molecules.

The number of cycles of β-oxidation is 8. When calculating, we get 8×5=40 ATP molecules.

An acid has 2 double bonds. Therefore, in two cycles of β-oxidation

2 FADH 2 molecules are not formed, which is equivalent to 4 ATP molecules. 2 macroergic bonds are spent on the activation of a fatty acid.

Thus, the energy yield is 108+40-4-2=142 ATP molecules.

Ketone bodies

Ketone bodies include three compounds of similar structure.

The synthesis of ketone bodies occurs only in the liver, the cells of all other tissues

(except erythrocytes) are their consumers.

The stimulus for the formation of ketone bodies is the intake of a large amount

fatty acids to the liver. As already mentioned, under conditions that activate

lipolysis in adipose tissue, about 30% of the formed fatty acids are retained by the liver. These conditions include starvation, type I diabetes mellitus, prolonged

nye physical activity, a diet rich in fats. Also, ketogenesis is enhanced by

catabolism of amino acids related to ketogenic (leucine, lysine) and mixed (phenylalanine, isoleucine, tyrosine, tryptophan, etc.).

During starvation, the synthesis of ketone bodies is accelerated by 60 times (up to 0.6 g / l), with diabetes mellitusItype - 400 times (up to 4 g / l).

Regulation of fatty acid oxidation and ketogenesis

1. Depends on the ratio insulin/glucagon. With a decrease in the ratio, lipolysis increases, the accumulation of fatty acids in the liver increases, which are actively

act in the reaction of β-oxidation.

With the accumulation of citrate and high activity of ATP-citrate-lyase (see below), the resulting malonyl-S-CoA inhibits carnitine acyl transferase, which prevents

contributes to the entry of acyl-S-CoA into mitochondria. Molecules present in the cytosol

acyl-S-CoA cells go to the esterification of glycerol and cholesterol, i.e. for the synthesis of fats.

In case of violation of the regulation malonyl-S-CoA synthesis is activated

ketone bodies, since the fatty acid that has entered the mitochondria can only be oxidized to acetyl-S-CoA. Excess acetyl groups are forwarded for synthesis

ketone bodies.

STORAGE OF FAT

Lipid biosynthesis reactions take place in the cytosol of the cells of all organs. Substrate

for the synthesis of fats de novo is glucose, which, entering the cell, is oxidized along the glycolytic pathway to pyruvic acid. Pyruvate in mitochondria is decarboxylated to acetyl-S-CoA and enters the TCA cycle. However, at rest,

rest, in the presence of a sufficient amount of energy in the cell of the TCA reaction (particularly

ity, isocitrate dehydrogenase reaction) are blocked by excess ATP and NADH. As a result, the first metabolite of TCA, citrate, is accumulated, moving into cy-

tozol. Acetyl-S-CoA formed from citrate is further used in biosynthesis

fatty acids, triacylglycerols and cholesterol.

Biosynthesis of fatty acids

The biosynthesis of fatty acids occurs most actively in the cytosol of liver cells.

nor, intestines, adipose tissue at rest or after eating. Conventionally, 4 stages of biosynthesis can be distinguished:

Formation of acetyl-S-CoA from glucose or ketogenic amino acids.

Transfer of acetyl-S-CoA from mitochondria to the cytosol.

in complex with carnitine, as well as higher fatty acids are transferred;

usually in the composition of citric acid, formed in the first reaction of the TCA.

Citrate coming from mitochondria is cleaved in the cytosol by ATP-citrate-lyase to oxaloacetate and acetyl-S-CoA.

Formation of malonyl-S-CoA.

Synthesis of palmitic acid.

It is carried out by a multi-enzymatic complex "fatty acid synthase" which includes 6 enzymes and an acyl-carrying protein (ACP). The acyl-carrying protein includes a derivative of pantothenic acid, 6-phosphopane-tetheine (PP), which has an SH group, similar to HS-CoA. One of the enzymes of the complex, 3-ketoacyl synthase, also has an SH group. The interaction of these groups determines the beginning of the biosynthesis of fatty acids, namely palmitic acid, which is why it is also called "palmitate synthase". Synthesis reactions require NADPH.

In the first reactions, malonyl-S-CoA is sequentially attached to the phospho-pantetheine of the acyl-carrying protein and acetyl-S-CoA to the cysteine ​​of 3-ketoacyl synthase. This synthase catalyzes the first reaction, the transfer of an acetyl group.

py on C2 malonyl with the elimination of the carboxyl group. Further into the keto group, the reaction

reduction, dehydration and again reduction turns into methylene with the formation of saturated acyl. Acyl transferase transfers it to

cysteine ​​of 3-ketoacyl synthase and the cycle is repeated until a palmitic residue is formed.

new acid. Palmitic acid is cleaved off by the sixth enzyme of the complex, thioesterase.

Fatty acid chain elongation

Synthesized palmitic acid, if necessary, enters the endo-

plasma reticulum or mitochondria. With the participation of malonyl-S-CoA and NADPH, the chain is extended to C18 or C20.

Polyunsaturated fatty acids (oleic, linoleic, linolenic) can also elongate with the formation of eicosanoic acid derivatives (C20). But double

ω-6-polyunsaturated fatty acids are synthesized only from the corresponding

predecessors.

For example, when forming ω-6 fatty acids of the series, linoleic acid (18:2)

dehydrogenates to γ-linolenic acid (18:3) and elongates to eicosotrienoic acid (20:3), the latter is further dehydrogenated to arachidonic acid (20:4).

For the formation of ω-3-series fatty acids, for example, timnodonic (20:5), it is necessary

The presence of α-linolenic acid (18:3) is expected, which dehydrates (18:4), lengthens (20:4) and dehydrates again (20:5).

Regulation of fatty acid synthesis

There are the following regulators of fatty acid synthesis.

Acyl-S-CoA.

first, by the principle of negative feedback inhibits the enzyme acetyl-S-CoA carboxylase, preventing the synthesis of malonyl-S-CoA;

Secondly, it suppresses citrate transport from mitochondria to cytosol.

Thus, the accumulation of acyl-S-CoA and its inability to react

esterification with cholesterol or glycerol automatically prevents the synthesis of new fatty acids.

Citrate is an allosteric positive regulator acetyl-S-

CoA carboxylase, accelerates the carboxylation of its own derivative - ace-tyl-S-CoA to malonyl-S-CoA.

covalent modification-

tion acetyl-S-CoA carboxylase by phosphorylation-

dephosphorylation. Participate-

cAMP-dependent protein kinase and protein phosphatase. Insu-

lin activates the protein

phosphatase and promotes the activation of acetyl-S-CoA-

carboxylase. Glucagon And address

naline by adenylate cyclase mechanism cause inhibition of the same enzyme and, consequently, of all lipogenesis.

SYNTHESIS OF TRIACYLGLYCEROLS AND PHOSPHOLIPIDS

General principles of biosynthesis

The initial reactions for the synthesis of triacylglycerols and phospholipids coincide and

occur in the presence of glycerol and fatty acids. As a result, synthesized

phosphatidic acid. It can be converted in two ways - CDF-DAG or dephosphorylated to DAG. The latter, in turn, is either acylated to

TAG, or binds to choline and forms PC. This PC contains saturated

fatty acid. This pathway is active in the lungs, where dipalmitoyl-

phosphatidylcholine, the main substance of the surfactant.

CDF-DAG, being the active form of phosphatidic acid, then turns into phospholipids - PI, PS, PEA, PS, cardiolipin.

At first glycerol-3-phosphate is formed and fatty acids are activated

Fatty acid coming from the blood at

the breakdown of HM, VLDL, HDL or synthesized in

cell de novo from glucose should also be activated. They are converted to acyl-S-CoA in ATP-

dependent reaction.

Glycerolin the liver is activated in the phosphorylation reaction using macroergic

ATP phosphate. IN muscles and adipose tissue this react-

cation is absent, therefore, in them, glycerol-3-phosphate is formed from dihydroxyacetone phosphate, a metabolite

glycolysis.

In the presence of glycerol-3-phosphate and acyl-S-CoA, phosphatidic acid.

Depending on the type of fatty acid, the resulting phosphatidic acid

If palmitic, stearic, palmitooleic, oleic acids are used, then phosphatidic acid is directed to the synthesis of TAG,

In the presence of polyunsaturated fatty acids, phosphatidic acid is

phospholipid precursor.

Synthesis of triacylglycerols

Biosynthesis of TAG liver increases under the following conditions:

a diet rich in carbohydrates, especially simple ones (glucose, sucrose),

an increase in the concentration of fatty acids in the blood,

high concentrations of insulin and low concentrations of glucagon,

the presence of a source of "cheap" energy, such as ethanol.

Synthesis of phospholipids

Biosynthesis of phospholipids compared with the synthesis of TAG has significant features. They consist in additional activation of PL components -

phosphatidic acid or choline and ethanolamine.

1. Activation choline(or ethanolamine) occurs through the intermediate formation of phosphorylated derivatives, followed by the addition of CMP.

In the next reaction, activated choline (or ethanolamine) is transferred to DAG

This pathway is characteristic of the lungs and intestines.

2. Activation phosphatidic acid consists in joining the CMF to it with

Lipotropic substances

All substances that promote the synthesis of PL and prevent the synthesis of TAG are called lipotropic factors. These include:

Structural components of phospholipids: inositol, serine, choline, ethanolamine, polyunsaturated fatty acids.

The donor of methyl groups for the synthesis of choline and phosphatidylcholine is methionine.

Vitamins:

B6, which promotes the formation of PEA from PS.

B12 and folic acid involved in the formation of the active form of methio-

With a lack of lipotropic factors in the liver, fatty infiltrate

walkie-talkie liver.

DISORDERS OF TRIACYLGLYCEROL METABOLISM

Fatty infiltration of the liver.

The main cause of fatty liver is metabolic block synthesis of VLDL. Since VLDL include heterogeneous compounds, the block

can occur at different levels of synthesis.

Apoprotein synthesis block - lack of protein or essential amino acids in food,

exposure to chloroform, arsenic, lead, CCl4;

block in the synthesis of phospholipids - the absence of lipotropic factors (vitamins,

methionine, polyunsaturated fatty acids);

assembly block of lipoprotein particles under the influence of chloroform, arsenic, lead, СCl4;

blocking the secretion of lipoproteins into the blood - СCl4, active peroxidation

lipids in case of deficiency of the antioxidant system (hypovitaminosis C, A,

There may also be a deficiency of apoproteins, fofolipids with a relative

excess substrate:

synthesis of an increased amount of TAG with an excess of fatty acids;

synthesis of an increased amount of cholesterol.

Obesity

Obesity is an excess of neutral fat in subcutaneous fat.

fiber.

There are two types of obesity - primary and secondary.

primary obesity is a consequence of hypodynamia and overeating.

In the body, the amount of food absorbed is regulated by the adipocyte hormone

leptin.Leptin is produced in response to an increase in fat mass in the cell

and ultimately reduces education neuropeptide Y(which encourages

search for food, and vascular tone and blood pressure) in the hypothalamus, which suppresses the food habit

denie. In 80% of obese individuals, the hypothalamus is insensitive to leptin. 20% have a defect in the structure of leptin.

Secondary obesity- occurs with hormonal diseases. To such

diseases include hypothyroidism, hypercortisolism.

A typical example of low pathogenic obesity is boron obesity.

sumo wrestlers. Despite the obvious excess weight, the sumo masters for a long time

They enjoy relatively good health due to the fact that they do not experience physical inactivity, and weight gain is associated exclusively with a special diet enriched with polyunsaturated fatty acids.

DiabetesIItype

The main cause of type II diabetes mellitus is a genetic predisposition

Presence - in relatives of the patient, the risk of getting sick increases by 50%.

However, diabetes will not occur unless there is a frequent and/or prolonged increase in blood glucose, which occurs when overeating. In this case, the accumulation of fat in the adipocyte is the "desire" of the body to prevent hyperglycemia. However, further insulin resistance develops, since the inevitable changes

adipocyte changes lead to disruption of insulin binding to receptors. At the same time, background lipolysis in the overgrown adipose tissue causes an increase

concentration of fatty acids in the blood, which contributes to insulin resistance.

Increasing hyperglycemia and insulin release lead to increased lipogenesis. Thus, two opposite processes - lipolysis and lipogenesis - enhance

and cause the development of type II diabetes mellitus.

The activation of lipolysis is also facilitated by the often observed imbalance between the intake of saturated and polyunsaturated fatty acids, so

how a lipid droplet in an adipocyte is surrounded by a monolayer of phospholipids, which must contain unsaturated fatty acids. In violation of the synthesis of phospholipids, the access of TAG-lipase to triacylglycerols is facilitated and their

hydrolysis is accelerated.

CHOLESTEROL METABOLISM

Cholesterol belongs to a group of compounds that have

based on a cyclopentanperhydrophenanthrene ring, and is an unsaturated alcohol.

Sources

Synthesis in the body is approximately 0.8 g/day,

while half of it is formed in the liver, about 15% in

intestine, the remainder in any cells that have not lost the nucleus. Thus, all body cells are capable of synthesizing cholesterol.

Of the foods richest in cholesterol (in terms of 100 g

product):

sour cream 0.002 g

butter 0.03 g

eggs 0.18 g

beef liver 0.44 g

whole day with food comes in on average 0,4 G.

Approximately 1/4 of the total cholesterol in the body is esterified polyne-

saturated fatty acids. In blood plasma, the ratio of cholesterol esters

to free cholesterol is 2:1.

breeding

Removal of cholesterol from the body occurs almost exclusively through the intestines:

with faeces in the form of cholesterol and neutral sterols formed by the microflora (up to 0.5 g / day),

in the form of bile acids (up to 0.5 g / day), while some of the acids are reabsorbed;

about 0.1 g is removed with the exfoliating epithelium of the skin and the secretion of the sebaceous glands,

approximately 0.1 g is converted into steroid hormones.

Function

Cholesterol is the source

steroid hormones - sex and adrenal cortex,

calcitriol,

bile acids.

In addition, it is a structural component of cell membranes and contributes

ordering into a phospholipid bilayer.

Biosynthesis

Occurs in the endoplasmic reticulum. The source of all carbon atoms in the molecule is acetyl-S-CoA, which comes here as part of citrate, as well as

in the synthesis of fatty acids. Cholesterol biosynthesis consumes 18 molecules

ATP and 13 NADPH molecules.

The formation of cholesterol occurs in more than 30 reactions, which can be grouped

feast in several stages.

Synthesis of mevalonic acid

Synthesis of isopentenyl diphosphate.

Synthesis of farnesyl diphosphate.

Synthesis of squalene.

Synthesis of cholesterol.

regulation of cholesterol synthesis

The main regulatory enzyme is hydroxymethylglutaryl-S-

CoA reductase:

firstly, according to the principle of negative feedback, it is inhibited by the final product of the reaction -

cholesterol.

Secondly, covalent

modification with hormonal

nal regulation: insu-

lin, by activating protein phosphatase, promotes

enzyme transition hydro-

hydroxy-methyl-glutaryl-S-CoA reductase into active

state. Glucagon and hell

renaline through the adenylate cyclase mechanism

ma activate protein kinase A, which phosphorylates the enzyme and translates

it to inactive form.

Transport of cholesterol and its esters.

Carried out by low and high density lipoproteins.

low density lipoproteins

general characteristics

Formed in the liver de novo and in the blood from VLDL

composition: 25% proteins, 7% triacylglycerols, 38% cholesterol esters, 8% free cholesterol,

22% phospholipids. The main apo protein is apoB-100.

normal content in the blood 3.2-4.5 g / l

the most atherogenic

Function

Transport XC into cells that use it for synthesis reactions of sex hormones (sex glands), gluco- and mineralocorticoids (adrenal cortex),

lecalciferol (skin), utilizing cholesterol in the form of bile acids (liver).

Transport of polyene fatty acids in the form of cholesterol esters in

some cells of loose connective tissue - fibroblasts, platelets,

endothelium, smooth muscle cells,

epithelium of the glomerular membrane of the kidneys,

bone marrow cells,

corneal cells,

neurocytes,

basophils of the adenohypophysis.

The peculiarity of this group of cells is the presence of lysosomal acidic hydrolase, decomposing cholesterol esters. Other cells do not have such enzymes.

On cells that use LDL, there is a high-affinity receptor specific for LDL - apoB-100 receptor. When LDL interacts with the receptor,

lipoprotein endocytosis and its lysosomal breakdown into its constituent parts - phospholipids, amino acids, glycerol, fatty acids, cholesterol and its esters.

Cholesterol is converted into hormones or incorporated into membranes. Excess membranes-

many cholesterol are removed with the help of HDL.

Exchange

In the blood, they interact with HDL, giving free cholesterol and receiving esterified cholesterol.

Interact with apoB-100 receptors in hepatocytes (about 50%) and tissues

(about 50%).

high density lipoproteins

general characteristics

are formed in the liver de novo, in blood plasma during the breakdown of chylomicrons, some

the second amount in the intestinal wall,

composition: 50% protein, 7% TAG, 13% cholesterol esters, 5% free cholesterol, 25% PL. The main apoprotein is apo A1

normal content in the blood 0.5-1.5 g / l

antiatherogenic

Function

Transport of cholesterol from tissues to the liver

A donor of polyenoic acids for the synthesis of phospholipids and eicosanoids in cells

Exchange

The LCAT reaction actively proceeds in HDL. In this reaction, the unsaturated fatty acid residue is transferred from PC to free cholesterol with the formation of lysophosphatidylcholine and cholesterol esters. Losing the phospholipid membrane HDL3 is converted into HDL2.

Interacts with LDL and VLDL.

LDL and VLDL are a source of free cholesterol for the LCAT reaction, in exchange they receive esterified cholesterol.

3. Through specific transport proteins, it receives free cholesterol from cell membranes.

3. Interacts with cell membranes, gives away part of the phospholipid shell, thus delivering polyene fatty acids to ordinary cells.

CHOLESTEROL METABOLIC DISORDERS

Atherosclerosis

Atherosclerosis is the deposition of cholesterol and its esters in the connective tissue of the walls

arteries, in which the mechanical load on the wall is expressed (in descending order

actions):

abdominal aorta

coronary artery

popliteal artery

femoral artery

tibial artery

thoracic aorta

thoracic aortic arch

carotid arteries

Stages of atherosclerosis

Stage 1 - damage to the endothelium.This is the "dolipid" stage, it is found

even in one year olds. Changes in this stage are nonspecific and can be caused by:

dyslipoproteinemia

hypertension

increased blood viscosity

viral and bacterial infections

lead, cadmium, etc.

At this stage, zones of increased permeability and adhesiveness are created in the endothelium.

bones. Outwardly, this manifests itself in loosening and thinning (up to the disappearance) of the protective glycocalyx on the surface of endotheliocytes, expansion of the interendo-

telial fissures. This leads to an increase in the release of lipoproteins (LDL and

VLDL) and monocytes in the intima.

Stage 2 - the stage of initial changes observed in most children and

young people.

Damaged endothelium and activated platelets produce inflammatory mediators, growth factors, and endogenous oxidants. As a result, monocytes penetrate even more actively through the damaged endothelium into the intima of the vessels and

contribute to the development of inflammation.

Lipoproteins in the area of ​​inflammation are modified by oxidation, glycosylation

ion, acetylation.

Monocytes, transforming into macrophages, absorb altered lipoproteins with the participation of "junk" receptors (scavenger receptors). The fundamental moment

The fact is that the absorption of modified lipoproteins goes without participation

apo-B-100 receptors, and, therefore, UNREGULATED ! In addition to macrophages, this way lipoproteins also enter smooth muscle cells, which are massively transferred

go into a macrophage-like form.

Accumulation of lipids in cells quickly exhausts the low capacity of cells to utilize free and esterified cholesterol. They are overflowing with

roids and turn into foamy cells. Externally on the endothelium appear whether-

Pimples and stripes.

Stage 3 - the stage of late changes.It is characterized by the following features

Benefits:

accumulation outside the cell of free cholesterol and esterified linoleic acid

(that is, as in plasma);

proliferation and death of foam cells, accumulation of intercellular substance;

cholesterol encapsulation and fibrous plaque formation.

Outwardly, it manifests itself as a protrusion of the surface into the lumen of the vessel.

Stage 4 - stage of complications.At this stage,

plaque calcification;

plaque ulceration leading to lipid embolism;

thrombosis due to platelet adhesion and activation;

vessel rupture.

Treatment

In the treatment of atherosclerosis, there should be two components: diet and medications. The goal of treatment is to reduce the concentration of total plasma cholesterol, LDL and VLDL cholesterol, increase HDL cholesterol.

Diet:

Food fats should include equal proportions of saturated, monounsaturated

polyunsaturated fats. The proportion of liquid fats containing PUFAs should be

at least 30% of all fats. The role of PUFAs in the treatment of hypercholesterolemia and atherosclerosis is reduced to

limited absorption of cholesterol in the small intestine

activation of bile acid synthesis,

decrease in the synthesis and secretion of LDL in the liver,

increase in HDL synthesis.

It has been established that if the ratio Polyunsaturated fatty acids equals 0.4, then

Saturated fatty acids

consumption of cholesterol in an amount up to 1.5 g per day does not lead to hypercholesterolemia

rolemia.

2. Consumption of high amounts of vegetables containing fiber (cabbage, sea-

cow, beet) to enhance intestinal motility, stimulate bile secretion and adsorption of cholesterol. In addition, phytosteroids competitively reduce cholesterol absorption,

however, they are not absorbed by themselves.

Sorption of cholesterol on fiber is comparable to that on special adsorbents.takh used as medicines (cholestyramine resins)

Medicines:

Statins (lovastatin, fluvastatin) inhibit HMG-S-CoA reductase, which reduces the synthesis of cholesterol in the liver by 2 times and accelerates its outflow from HDL to hepatocytes.

Suppression of absorption of cholesterol in the gastrointestinal tract - anion exchange

resins (Cholestyramine, Cholestide, Questran).

Nicotinic acid preparations inhibit the mobilization of fatty acids from

depot and reduce the synthesis of VLDL in the liver, and, consequently, the formation of

LDL in the blood

Fibrates (clofibrate, etc.) increase the activity of lipoprotein lipase,

catabolism of VLDL and chylomicrons, which increases the transition of cholesterol from

them into HDL and its evacuation to the liver.

Preparations of ω-6 and ω-3 fatty acids (Linetol, Essentiale, Omeganol, etc.)

increase the concentration of HDL in plasma, stimulate bile secretion.

Suppression of enterocyte function with the antibiotic neomycin, which

reduces fat absorption.

Surgical removal of the ileum and cessation of bile acid reabsorption.

DISORDERS OF LIPOPROTEIN METABOLISM

Changes in the ratio and number of lipoprotein classes are not always consistent with

are driven by hyperlipidemia, therefore, the identification of dyslipoproteinemia.

The causes of dyslipoproteinemia may be a change in the activity of enzymes

lipoprotein metabolism - LCAT or LPL, reception of LP on cells, impaired synthesis of apoproteins.

There are several types of dyslipoproteinemia.

TypeI: Hyperchylomicronemia.

Caused by genetic deficiency lipoprotein lipase.

Laboratory indicators:

an increase in the number of chylomicrons;

normal or slightly elevated content of preβ-lipoproteins;

a sharp increase in the level of TAG.

CS / TAG ratio< 0,15

Clinically manifested at an early age by xanthomatosis and hepatosplenomega-

Lia as a result of lipid deposition in the skin, liver and spleen. Primary type I hyperlipoproteinemia is rare and manifests at an early age, secondary- accompanies diabetes, lupus erythematosus, nephrosis, hypothyroidism, manifested by obesity.

TypeII: Hyper-β - lipoproteinemia

Formation of glycerol-3-phosphate

The synthesis of fats in the liver and adipose tissue proceeds through the formation of an intermediate product - phosphatidic acid (Fig. 8-21).

The precursor of phosphatidic acid is glycerol-3-phosphate, which is formed in the liver in two ways:

• reduction of dihydroxyacetone phosphate, an intermediate metabolite of glycolysis;
• phosphorylation by glycerol kinase of free glycerol entering the liver from the blood (the product of the action of LP-lipase on the fats of HM and VLDL).

In adipose tissue, glycerol kinase is absent, and the reduction of dihydroxyacetone phosphate is the only way to form glycerol-3-phosphate. Therefore, fat synthesis in adipose tissue can only occur during the absorptive period, when glucose enters adipocytes with the help of the glucose transporter protein GLUT-4, which is active only in the presence of insulin, and decomposes along the glycolysis pathway.

Synthesis of fats in adipose tissue

In adipose tissue, for the synthesis of fats, mainly fatty acids released during the hydrolysis of fats of XM and VLDL are used (Fig. 8-22). Fatty acids enter adipocytes, are converted into CoA derivatives and interact with glycerol-3-phosphate, forming first lysophosphatidic acid and then phosphatidic acid. Phosphatidic acid after dephosphorylation turns into diacylglycerol, which is acylated to form triacylglycerol.

In addition to fatty acids entering adipocytes from the blood, these cells also synthesize fatty acids from glucose breakdown products. In adipocytes, to ensure fat synthesis reactions, glucose breakdown occurs in two ways: glycolysis, which provides the formation of glycerol-3-phosphate and acetyl-CoA, and the pentose phosphate pathway, the oxidative reactions of which provide the formation of NADPH, which serves as a hydrogen donor in fatty acid synthesis reactions.

Fat molecules in adipocytes aggregate into large water-free fat droplets and are therefore the most compact form of storage for fuel molecules. It has been calculated that if the energy stored in fats were stored in the form of highly hydrated glycogen molecules, then a person's body weight would increase by 14-15 kg.

Rice. 8-21. Synthesis of fats in the liver and adipose tissue.

TAG synthesis in the liver. Formation of VLDL in the liver and transport of fats to other tissues

The liver is the main organ where fatty acids are synthesized from glycolysis products. In the smooth ER of hepatocytes, fatty acids are activated and immediately used for fat synthesis by interacting with glycerol-3-phosphate. As in adipose tissue, fat synthesis occurs through the formation of phosphatidic acid. The fats synthesized in the liver are packed into VLDL and secreted into the blood (Fig. 8-23).

The composition of VLDL, in addition to fats, includes cholesterol, phospholipids and protein - apoB-100. It is a very "long" protein containing 11,536 amino acids. One molecule of apoB-100 covers the surface of the entire lipoprotein.

VLDLP from the liver are secreted into the blood (Fig. 8-23), where they, like HM, are affected by LP-lipase. Fatty acids enter tissues, in particular adipocytes, and are used for the synthesis of fats. In the process of fat removal from VLDL, under the action of LP-lipase, VLDL is first converted into LSHP, and then into LDL. In LDL, the main lipid components are cholesterol and its esters, so LDL are lipoproteins that deliver cholesterol to peripheral tissues. Glycerol, released from lipoproteins, is transported by the blood to the liver, where it can again be used for the synthesis of fats.

The rate of synthesis of fatty acids and fats in the liver significantly depends on the composition of the food. If the food contains more than 10% fat, then the rate of fat synthesis in the liver is sharply reduced.

B. Hormonal regulation of synthesis
and fat mobilization

Synthesis and secretion of VLDL in the liver. Proteins synthesized in the rough ER (1), in the Golgi apparatus (2), form a complex with TAG, called VLDL, VLDL are assembled in secretory granules (3), transported to the cell membrane and secreted into the blood

regulation of fat synthesis. In the absorptive period, with an increase in the ratio of insulin / glucagon in the liver, fat synthesis is activated. In adipose tissue, the synthesis of LP-lipase in adipocytes is induced and its exposure to the surface of the endothelium is carried out; therefore, during this period, the supply of fatty acids to adipocytes increases. At the same time, insulin activates glucose transport proteins - GLUT-4. Glucose entry into adipocytes and glycolysis are also activated. As a result, all the necessary components for the synthesis of fats are formed: glycerol-3-phosphate and active forms of fatty acids. In the liver, insulin, acting through various mechanisms, activates enzymes by dephosphorylation and induces their synthesis. As a result, the activity and synthesis of enzymes involved in the conversion of part of the glucose from food into fats increase. These are the regulatory enzymes of glycolysis, the pyruvate dehydrogenase complex, and the enzymes involved in the synthesis of fatty acids from acetyl-CoA. The result of the action of insulin on the metabolism of carbohydrates and fats in the liver is an increase in the synthesis of fats and their secretion into the blood as part of VLDL. VLDL deliver fats to the capillaries of adipose tissue, where the action of Lp-lipase ensures the rapid entry of fatty acids into adipocytes, where they are deposited as part of triacylglycerols.

54V. Hormonal regulation of synthesis
and fat mobilization

Which process will prevail in the body - the synthesis of fats (lipogenesis) or their breakdown (lipolysis), depends on the intake of food and physical activity. In the absorptive state, lipogenesis occurs under the action of insulin; in the postabsorptive state, lipolysis is activated by glucagon. Adrenaline, whose secretion increases with physical activity, also stimulates lipolysis.

regulation of fat synthesis. In the absorption period, with an increase in the ratio of insulin /

Rice. 8-23. Synthesis and secretion of VLDL in the liver. Proteins synthesized in the rough ER (1), in the Golgi apparatus (2), form a complex with TAG, called VLDL, VLDL are assembled in secretory granules (3), transported to the cell membrane and secreted into the blood.

glucagon in the liver activates the synthesis of fats. In adipose tissue, the synthesis of LP-lipase in adipocytes is induced and its exposure to the surface of the endothelium is carried out; therefore, during this period, the supply of fatty acids to adipocytes increases. At the same time, insulin activates glucose transport proteins - GLUT-4. Glucose entry into adipocytes and glycolysis are also activated. As a result, all the necessary components for the synthesis of fats are formed: glycerol-3-phosphate and active forms of fatty acids. In the liver, insulin, acting through various mechanisms, activates enzymes by dephosphorylation and induces their synthesis. As a result, the activity and synthesis of enzymes involved in

in the conversion of part of the glucose that comes with food into fats. These are the regulatory enzymes of glycolysis, the pyruvate dehydrogenase complex, and the enzymes involved in the synthesis of fatty acids from acetyl-CoA. The result of the action of insulin on the metabolism of carbohydrates and fats in the liver is an increase in the synthesis of fats and their secretion into the blood as part of VLDL. VLDL deliver fats to the capillaries of adipose tissue, where the action of Lp-lipase ensures the rapid entry of fatty acids into adipocytes, where they are deposited as part of triacylglycerols.

The storage of fats in adipose tissue is the main form of deposition of energy sources in the human body (Tables 8-6). The reserves of fat in the body of a person weighing 70 kg are 10 kg, but in many people the amount of fat can be much higher.

Fats form fat vacuoles in adipocytes. Fat vacuoles sometimes fill a significant part of the cytoplasm. The rate of synthesis and mobilization of subcutaneous fat occurs unevenly in different parts of the body, due to the uneven distribution of hormone receptors on adipocytes.

regulation of fat mobilization. The mobilization of deposited fats is stimulated by glucagon and adrenaline and, to a lesser extent, by some other hormones (somatotropic, cortisol). In the postabsorptive period and during starvation, glucagon, acting on adipocytes through the adenylate cyclase system, activates protein kinase A, which phosphorylates and thus activates hormone-sensitive lipase, which initiates lipolysis and the release of fatty acids and glycerol into the blood. During physical activity, the secretion of adrenaline increases, which acts through the β-adrenergic receptors of adipocytes, which activate the adenylate cyclase system (Fig. 8-24). Currently, 3 types of β-receptors have been discovered: β 1 , β 2 , β 3 , the activation of which leads to a lipolytic effect. The activation of β 3 receptors leads to the greatest lipolytic effect. Adrenaline simultaneously acts on α 2 adipocyte receptors associated with an inhibitory G-protein, which inactivates the adenylate cyclase system. Probably, the action of adrenaline is twofold: at low concentrations in the blood, its antilipolytic action through α 2 receptors predominates, and at high concentrations, its lipolytic action through β receptors predominates.

For muscles, heart, kidneys, liver, during fasting or physical work, fatty acids become an important source of energy. The liver converts some of the fatty acids into ketone bodies used by the brain, nervous tissue and some other tissues as energy sources.

As a result of fat mobilization, the concentration of fatty acids in the blood increases by approximately 2 times (Fig. 8-25), however, the absolute concentration of fatty acids in the blood is low even during this period. T 1/2 fatty acids in the blood is also very small (less than 5 minutes), which means that there is a rapid flow of fatty acids from adipose tissue to other organs. When the post-absorptive period is replaced by abortive, insulin activates a specific phosphatase, which dephosphorylates the hormone-sensitive lipase, and the breakdown of fats stops.

VIII. METABOLISM AND FUNCTIONS OF PHOSPHOLIPIDS

The metabolism of phospholipids is closely related to many processes in the body: the formation and destruction of cell membrane structures, the formation of LP, bile micelles, the formation of a surface layer in the alveoli of the lungs, which prevents the alveoli from sticking together during exhalation. Phospholipid metabolism disorders are the cause of many diseases, in particular, respiratory distress syndrome of newborns, fatty hepatosis, hereditary diseases associated with the accumulation of glycolipids - lysosomal diseases. In lysosomal diseases, the activity of hydrolases localized in lysosomes and involved in the breakdown of glycolipids decreases.

A. Glycerophospholipid metabolism