Lipid metabolism is a fat metabolism that takes place in the organs of the digestive tract with the participation of enzymes produced by the pancreas. If this process is disrupted, symptoms may vary depending on the nature of the failure - an increase or decrease in lipid levels. With this dysfunction, the amount of lipoproteins is examined, since they can identify the risk of developing cardiovascular diseases. Treatment is determined strictly by the doctor based on the results obtained.

What is lipid metabolism?

When entering the body along with food, fats undergo primary processing in the stomach. However, complete digestion does not occur in this environment, since it is highly acidic but lacks bile acids.

Lipid metabolism scheme

When they enter the duodenum, which contains bile acids, the lipids undergo emulsification. This process can be described as partial mixing with water. Since the environment in the intestines is slightly alkaline, the acidic contents of the stomach are loosened under the influence of released gas bubbles, which are a product of the neutralization reaction.

The pancreas synthesizes a specific enzyme called lipase. It is he who acts on fat molecules, breaking them down into two components: fatty acids and glycerol. Typically, fats are transformed into polyglycerides and monoglycerides.

Subsequently, these substances enter the epithelium of the intestinal wall, where the biosynthesis of lipids necessary for the human body occurs. They then combine with proteins to form chylomicrons (a class of lipoproteins), after which they are distributed throughout the body along with the flow of lymph and blood.

In body tissues, the reverse process of obtaining fats from blood chylomicrons occurs. The most active biosynthesis occurs in the fat layer and liver.

Symptoms of a disrupted process

If lipid metabolism is disturbed in the human body, the result is various diseases with characteristic external and internal signs. The problem can only be identified after laboratory tests.

Impaired fat metabolism can manifest itself in the following symptoms of elevated lipid levels:

• the appearance of fatty deposits in the corners of the eyes;
• increased volume of the liver and spleen;
• increased body mass index;
• manifestations characteristic of nephrosis, atherosclerosis, endocrine diseases;
• increased vascular tone;
• formation of xanthomas and xanthelasmas of any localization on the skin and tendons. The first are nodular neoplasms containing cholesterol. They affect the palms, feet, chest, face and shoulders. The second group also represents cholesterol neoplasms, which have a yellow tint and appear on other areas of the skin.

When lipid levels are low, the following symptoms appear:

• weight loss;
• separation of the nail plates;
• hair loss;
• nephrosis;
• disorders of the menstrual cycle and reproductive functions in women.

Lipidogram

Cholesterol moves in the blood along with proteins. There are several types of lipid complexes:

1. 1. Low-density lipoproteins (LDL). They are the most harmful fraction of lipids in the blood, with a high ability to form atherosclerotic plaques.
2. 2. High density lipoproteins (HDL). They have the opposite effect, preventing the formation of deposits. They transport free cholesterol to liver cells, where it is subsequently processed.
3. 3. Very low density lipoproteins (VLDL). They are the same harmful atherogenic compounds as LDL.
4. 4. Triglycerides. They are fatty compounds that are a source of energy for cells. When they are excessive in the blood, the vessels are predisposed to atherosclerosis.

Assessing the risk of developing cardiovascular diseases by cholesterol levels is not effective if a person has a disorder of lipid metabolism. With a predominance of atherogenic fractions over conditionally harmless ones (HDL), even with normal cholesterol levels, the likelihood of developing atherosclerosis seriously increases. Therefore, if fat metabolism is disturbed, a lipid profile should be performed, that is, blood biochemistry (analysis) should be performed to determine the amount of lipids.

Based on the obtained indicators, the atherogenicity coefficient is calculated. It shows the ratio of atherogenic and non-atherogenic lipoproteins. Defined as follows:

Formula for calculating the atherogenic coefficient

Normally, KA should be less than 3. If it is between 3 and 4, then there is a high risk of developing atherosclerosis. When the value is exceeded 4, progression of the disease is observed.

Constant turmoil, dry food, passion for semi-finished products are a characteristic feature of modern society. As a rule, an unhealthy lifestyle leads to weight gain. In such cases, doctors often state that a person’s lipid metabolism is disturbed. Of course, many people do not have such specific knowledge and have no idea what lipid metabolism is.

What are lipids?

Meanwhile, lipids are present in every living cell. These biological molecules, which are organic substances, share a common physical property - insolubility in water (hydrophobicity). Lipids are made up of various chemicals, but the bulk of them are fats. The human body is so wisely designed that it is able to synthesize most of the fats on its own. But essential fatty acids (for example, linoleic acid) must enter the body from the outside through food. Lipid metabolism occurs at the cellular level. This is a rather complex physiological and biochemical process, consisting of several stages. First, lipids are broken down, then absorbed, after which intermediate and final exchange occurs.

Split

In order for the body to absorb lipids, they must first be broken down. First, food that contains lipids enters the oral cavity. There it is moistened with saliva, mixed, crushed and forms a food mass. This mass enters the esophagus, and from there into the stomach, where it is saturated with gastric juice. In turn, the pancreas produces lipase, a lipolytic enzyme that is capable of breaking down emulsified fats (that is, fats mixed with a liquid medium). Then the semi-liquid food mass enters the duodenum, then into the ileum and jejunum, where the digestion process ends. Thus, pancreatic juice, bile and gastric juice are involved in the breakdown of lipids.

Suction

After digestion, lipid absorption begins, which occurs primarily in the upper small intestine and lower duodenum. There are no lipolytic enzymes in the large intestine. The products formed after the breakdown of lipids are glycerophosphates, glycerol, higher fatty acids, monoglycerides, diglycerides, cholesterol, nitrogenous compounds, phosphoric acid, higher alcohols and small fat particles. All these substances are absorbed by the epithelium of the intestinal villi.

Intermediate and final exchange

Intermediate metabolism is a combination of several very complex biochemical processes, among which it is worth highlighting the conversion of triglycerides into higher fatty acids and glycerol. The final stage of intermediate metabolism is the metabolism of glycerol, the oxidation of fatty acids and the biological synthesis of other lipids.

At the last stage of metabolism, each group of lipids has its own specificity, but the main products of final metabolism are water and carbon dioxide. Water leaves the body naturally, through sweat and urine, and carbon dioxide leaves the body through the lungs when exhaling air. This completes the process of lipid metabolism.

Lipid metabolism disorder

Any disorder in the process of fat absorption indicates a disorder in lipid metabolism. This may be due to insufficient intake of pancreatic lipase or bile into the intestines, as well as hypovitaminosis, obesity, atherosclerosis, various diseases of the gastrointestinal tract and other pathological conditions. When the villous epithelial tissue in the intestine is damaged, fatty acids are no longer fully absorbed. As a result, a large amount of undigested fat accumulates in the stool. The stool takes on a characteristic whitish-gray color.

Of course, with the help of diet and cholesterol-lowering medications, lipid metabolism can be corrected and improved. You will need to regularly monitor the concentration of triglycerides in your blood. However, it should be remembered that the human body only needs a small amount of fat. To prevent lipid metabolism disorders, you should reduce the consumption of meat, oil, offal and give preference to fish and seafood. Lead an active lifestyle, move more, adjust your weight. Be healthy!

Abbreviations

TAG - triacylglycerols

PL – phospholipids CS – cholesterol

cHC - free cholesterol

ECS – esterified cholesterol PS – phosphatidylserine

PC – phosphatidylcholine

PEA – phosphatidylethanolamine PI – phosphatidylinositol

MAG – monoacylglycerol

DAG – diacylglycerol PUFA – polyunsaturated fatty acids

FA – fatty acids

CM - chylomicrons LDL - low-density lipoproteins

VLDL – very low density lipoproteins

HDL – high density lipoproteins

CLASSIFICATION OF LIPIDS

The ability to classify lipids is difficult, since the class of lipids includes substances that are very diverse in their 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 CS derivatives.

In human fat, fatty acids are characterized by the following features:

an even number of carbon atoms in the chain,

no chain branches

the presence of double bonds only in cis-conformation

in turn, the fatty acids themselves are heterogeneous and vary length

chain and quantity double bonds.

TO rich fatty acids include palmitic (C16), stearic

(C18) and arachine (C20).

TO monounsaturated– palmitoleic (C16:1), oleic (C18:1). 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 the differences in quantity double bonds, acids differentiate them 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 polylinear

saturated fatty acids are divided into

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

arachidonic (C20:4, 5,8,11,14). These acids form vitamin F, and co-

kept in vegetable oils.

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

pentaenoic acid, C20;5, 5,8,11,14,17), clupanodonic acid (docosopentaenoic acid, C22:5,

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

a more significant source of acids of this group is cold fish oil

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

nom, flaxseed, corn oils.

The role of fatty acids

The most famous function of lipids, energy, is associated with fatty acids.

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

half of all energy (see β-oxidation), only red blood cells 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 eicosotriene (C20:3), arachidonic (C20:4), thymnodonic (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) -synthesized in almost all cells, except 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 varies 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. They are synthesized in the endothelium of myocardial vessels, uterus, and gastric mucosa.

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

cause 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 sti-

They stimulate motility, chemotaxis and migration of cells to the site of inflammation; in general, they activate inflammatory reactions, preventing its chronicization. Cause co-

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

Addition

Depending on the source 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.

I wonder whatPgE1 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 come from thymnodonic acid, by number

double bonds are assigned indexes of 3 or 5: e.g.Pg E3, Pg I3, Tx A3, Lt A5

The division of eicosanoids into groups has clinical significance. This is especially evident in the example of prostacyclins and thromboxanes:

	Original	Number	Activity	Activity
	fat	double bonds
			prostacyclins	thromboxanes
	acid	in a molecule
	γ -Linolenova
	I C18:3,
	Arachidonic
	Timnodono-		increase	decreasing
			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 reduce viscosity.

bones, reduce thrombosis, dilates blood vessels and improves blood

supply of fabrics.

1. Researchers' attention to ω -3 acids were attracted by the Eskimo phenomenon, co-

native inhabitants of Greenland and the peoples of the Russian Arctic. Against the background of high consumption of animal protein and fat and a very small amount of plant products, a number of positive features were noted:

no incidence of atherosclerosis, coronary disease

heart and myocardial infarction, stroke, hypertension;

increased HDL content in the blood plasma, decreased concentrations of total cholesterol and LDL;

reduced platelet aggregation, low blood viscosity

different fatty acid composition of cell membranes compared to Europeans

mi - C20:5 was 4 times more, C22:6 16 times!

This condition was calledANTIATEROSCLEROSIS .

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

prevented death in experimental ratsβ - pancreatic cells 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 (improved conductivity and rhythm),

peripheral circulatory disorder

Triacylglycerols

Triacylglycerols (TAGs) are the most abundant lipids in

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

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

vital activity for 40 days of complete fasting;

heat-saving;

mechanical protection.

Addition

The function of triacylglycerols is illustrated by the care requirements

premature babies who have not yet developed a fat layer - they need to be fed more often, and additional measures must be taken to prevent the baby from hypothermia

TAG contains triatomic alcohol glycerol and three fatty acids. Fat-

nic 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 humans it is 64, for cream margarine it is 63, for hemp oil it is 150.

Based on their structure, simple and complex TAGs can be distinguished. In simple TAGs all fat is

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

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

Rancidity of fats

Rancidity of fats is a common definition of 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) are formed hydroperoxides(ROOH). In the body, this is counteracted by antioxidant systems.

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

dismutase.

Phospholipids

Phosphatidic acid (PA)–intermediate co-

combination for the synthesis of TAG and PL.

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

structural PL, together with cholesterol form lipid

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

Besides, dipalmitoylphosphatidylcholine, being

surfactant, serves as the main component surfactant

pulmonary alveoli. Its deficiency in the lungs of premature infants leads to the development of syn-

Droma of respiratory failure. Another function of the farm is its participation in education bile and maintaining the cholesterol present in it in a dissolved state

Phosphatidylinositol (PI)– plays a leading role in phospholipid-calcium

mechanism of hormonal signal transmission into the cell.

Lysophospholipids– product of hydrolysis of phospholipids by phospholipase A2.

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

10% phospholipids of brain and muscle tissue.

Sphingomyelins-The majority of them are located in the nervous tissue.

EXTERNAL LIPID METABOLISM.

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

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

Triacylglycerols, phospholipids and cholesterol esters come from food.

Oral cavity.

It is generally accepted that lipid digestion does not occur in the mouth. However, there is evidence of the secretion of tongue lipase by Ebner's glands in infants. The stimulus for the secretion of lingual lipase is the 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

In an adult, the stomach's own lipase does not play a significant role in the digestion

cooking lipids 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 lipase contained in mammary milk.

teri. There is no lipase in cow's milk.

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

which is important for further digestion of fats in the intestines. Availability of 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 the 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-

lyses 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 acid.

Until the age of 7 years, the activity of pancreatic lipase is low and reaches a maximum by

pancreatic juice also contains active

trypsin-regulated phospholipase A2, discovered

activity of phospholipase C and lysophospholipase. The resulting lysophospholipids are

good surfactant, so

They contribute to the emulsification of dietary fats and the formation of micelles.

intestinal juice contains phospho-

lipases A2 and C.

For phospholipases to function, Ca2+ ions are required to facilitate the removal of

fatty acids from the catalysis zone.

The hydrolysis of cholesterol esters is carried out by cholesterol esterase of pancreatic juice.

Bile

Compound

Bile has an alkaline reaction. It contains a dry residue of about 3% and water of 97%. Two groups of substances are found in the dry residue:

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

bilirubin and bile acids actively secreted by hepatocytes.

normally there is a relationship bile acids : FH : HS equal 65:12:5 .

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

The role of bile

Along with pancreatic juice neutralization sour chyme, I do-

from the stomach. In this case, 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 of

nation [bile acids, unsaturated acids and MAG];

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

formation of micelles and liposomes capable of absorption.

Thanks to paragraphs 1 and 2, it ensures the absorption of fat-soluble substances 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% of cholesterol formed in

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

Nose C Guinea pigs developed except for scurvy, atherosclerosis and cholelithiasis disease. This is due to the retention of cholesterol in cells and impaired dissolution of it in

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

are expressed in the form of paired compounds with glycine - glycoderivatives and with taurine - tauroderivatives, 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. 6-10 such cycles occur per day. Thus,

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

lipids supplied during the day.

Bile formation disorder

Impaired bile formation is most often associated with a chronic excess of cholesterol in the body, since bile is the only way to eliminate it. As a result of a violation of the relationship 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, a lack of phospholipids or bile acids plays a role in the development of the disease when their synthesis is disrupted. Stagnation in the gallbladder, which occurs due to improper nutrition, leads to thickening of bile due to the reabsorption of water through the wall; lack of water in the body also aggravates 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 existing 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

They 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 enterocyte function (neomycin) – decreased fat absorption.

Surgical removal of the ileum and cessation of reabsorption

bile acids.

Absorption of lipids.

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

Short fatty acids are absorbed directly without any additional mechanisms.

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.

There is no established understanding regarding the mechanism of lipid absorption itself. First point vision is that micelles penetrate inside

cells entirely by diffusion without energy consumption. The cells are breaking down

micelles and the release of bile acids into the blood, FA and MAG remain and form TAG. At another point vision, The absorption of micelles occurs by pinocytosis.

And finally Thirdly, only lipid complexes can penetrate into the cell

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

Digestion and absorption problems may occur

for diseases of the liver and gall bladder, pancreas, intestinal wall,

damage to enterocytes by 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 that fall here, endogenous fatty acids can also be partially used.

During synthesis triacylglycerols received

fatty acid is activated through the addition of co-

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

reads along two possible paths.

First way–2-monoacylglyceride,occurs with the participation of exogenous 2-MAG 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 FA, it is activated 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 enterocytes and enters the blood.

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

Phospholipids are resynthesized in two ways: using 1,2-MAG 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 blood as part of special particles - lipoproteins.The surface of the particles is hydrophilic and formed by proteins, phospholipids and free cholesterol. Triacylglycerols and cholesterol esters make up the hydrophobic core.

The proteins in lipoproteins are usually called apowhites There are several types of them - A, B, C, D, E. Each class of lipoproteins contains corresponding apoproteins that perform structural, enzymatic and cofactor functions.

Lipoproteins differ in the ratio

research on triacylglycerols, cholesterol and its

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

chylomicrons (CM);

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 TAG from the intestine to tissues occurs in the form of chylomicrons, and from the liver to tissues in the form of very low density lipoproteins.

Chylomicrons

general characteristics

are 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.

Normally they are not detected on an empty stomach, they appear in the blood after eating,

coming from the lymph through the thoracic lymphatic duct, and completely disappears -

out in 10-12 hours.

not atherogenic

Function

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

chewing fats, mostly international

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

brain, kidneys, spleen, macrophages

Disposal

On the endothelium of capillaries there is a higher

of the listed fabrics is fer-

cop lipoprotein lipase, attach-

attached to the membrane by glycosaminoglycans. It hydrolyzes TAG contained in chylomicrons to free

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

liver and are destroyed.

Very low density lipoproteins

general characteristics

synthesized into 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 TAG 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 lipases, after which residual VLDL are either evacuated to the liver or converted into another type of lipoprotein - low-lipoprotein

density (LDL).

MOBILIZATION OF FAT

IN at rest 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 lipolysis of TAG.

Hormone-dependent activation of lipolysis

At voltage body (fasting, prolonged muscular work, cooling

denition) 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 does not manifest itself due to the lack of substrates.

As a result of lipolysis, free glycerol And fatty acid. Glycerol delivered with blood to the liver and kidneys, here it is phosphorylated and turns into a metabolite of glycolysis, glyceraldehyde phosphate. Depending on the

loviy GAF can be included in gluconeogenesis reactions (during fasting, muscle exercise) or oxidized to pyruvic acid.

Fatty acid transported in combination with blood plasma albumin

during physical activity - into the muscles

during fasting - into most tissues and about 30% are captured by the liver.

During fasting and physical activity, after penetration into cells, fatty acids

slots enter the β-oxidation pathway.

β - oxidation of fatty acids

β-oxidation reactions occur

mitochondria of most cells in the body. For oxidation use

there are fatty acids supplied

cytosol from the blood or during intracellular TAG lipolysis.

Before entering the mat-

rix of mitochondria and oxidize, the fatty acid must activate-

Xia.This is done by connecting

lack of coenzyme A.

Acyl-S-CoA is a high-energy

genetic compound. Irreversible

The reaction power is achieved by hydrolysis of diphosphate into two molecules

phosphoric acid pyrophosphoric acid

Acyl-S-CoA synthetases are located

in the endoplasmic reticulum

me, 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 able to pass through

die through the mitochondrial membrane

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

non-like substance carnithi-

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

acyl transferaseI.

After binding to carnitine, the fatty acid is transported through

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

cop carnitine acyl transferase II

again forms acyl-S-CoA which

enters the β-oxidation pathway.

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

chesically In them there are sequential

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

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

reactions and everything repeats again, until

as long as the last cycle produces two acetyl-S-CoAs.

Oxidation of unsaturated fatty acids

When unsaturated fatty acids are oxidized, the cell needs

additional isomerase enzymes. These isomerases move double bonds in fatty acid residues from γ- to β-position, convert natural double

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 participates, 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.

vegetable food and seafood. Their oxidation occurs along the usual path to

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

succinyl-S-CoA. Biotin and vitamin B12 are involved in these reactions.

Energy balance β -oxidation.

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

must be taken into account

number of β-oxidation cycles. The number of β-oxidation cycles is easy to imagine based on the concept 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 a fatty acid. In the first β-oxidation reaction, a double bond is formed with the participation of FAD. If a double bond is already present in the fatty acid, then there is no need for this reaction and FADH2 is not formed. The remaining reactions of the cycle proceed without changes.

amount of energy spent on activation

Example 1. Oxidation of palmitic acid (C16).

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

Since there are 16 carbon atoms, β-oxidation produces 8 molecules of acetyl-S-CoA. The latter enters the TCA cycle, during its oxidation in one revolution of the cyclic

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

ribbon of 12 ATP molecules. Just 8 molecules of acetyl-S-CoA will provide the formation of 96 molecules of ATP.

There are no double bonds in palmitic acid.

To activate a fatty acid, 1 molecule of ATP is used, which, however, is hydrolyzed to AMP, that is, 2 high-energy bonds are wasted.

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. This means 9×12=108 ATP molecules.

The number of β-oxidation cycles 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 FADN 2 molecules are not formed, which is equivalent to 4 ATP molecules. 2 macroergic bonds are spent on fatty acid activation.

Thus, the energy output 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; cells of all other tissues

(except for erythrocytes) are their consumers.

The stimulus for the formation of ketone bodies is the intake of large amounts of

quality of fatty acids in the liver. As already indicated, in conditions that activate

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

intense physical activity, diet rich in fats. Ketogenesis also increases with

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

During fasting, the synthesis of ketone bodies accelerates 60 times (up to 0.6 g/l); in diabetes mellitusItype – 400 times (up to 4 g/l).

Regulation of fatty acid oxidation and ketogenesis

1. Depends on the ratio insulin/glucagon. As the ratio decreases, lipolysis increases and the accumulation of fatty acids in the liver increases, which actively

enter β-oxidation reactions.

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

promotes the entry of acyl-S-CoA into mitochondria. The molecules present in the cytosol

Acyl-S-CoA molecules are used for the esterification of glycerol and cholesterol, i.e. for the synthesis of fats.

In case of dysregulation on the part of malonyl-S-CoA synthesis is activated

ketone bodies, since the fatty acid that enters the mitochondria can only be oxidized to acetyl-S-CoA. Excess acetyl groups are transferred to synthesis

ketone bodies.

STORING FAT

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

For de novo fat synthesis, glucose is used, which enters the cell and is oxidized through the glycolytic pathway to pyruvic acid. Pyruvate in mitochondria is decarboxylated into acetyl-S-CoA and enters the TCA cycle. However, at rest, with

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

ity, isocitrate dehydrogenase reaction) are blocked by excess ATP and NADH. As a result, the first metabolite of the TCA cycle accumulates, citrate, which moves into the circulation.

Tosol. 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 most actively occurs in the cytosol of liver cells.

neither, 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 combination with carnitine, in the same way as higher fatty acids are transported;

usually as part of the citric acid formed in the first reaction of the TCA cycle.

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

Formation of malonyl-S-CoA.

Synthesis of palmitic acid.

It is carried out by the multienzyme complex “fatty acid synthase”, which includes 6 enzymes and an acyl-transfer protein (ATP). The acyl-transfer protein includes a pantothenic acid derivative, 6-phosphopane-teteine ​​(PT), which has an SH group, like 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 acid, 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 added to the phospho-panthetheine of the acyl-transfer protein and acetyl-S-CoA is added to the cysteine ​​of the 3-ketoacyl synthase. This synthase catalyzes the first reaction – the transfer of an acetyl group

ps on C2 of malonyl with elimination of the carboxyl group. Next, the keto group reacts

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

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

new acid. Palmitic acid is cleaved 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 be lengthened to form 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, linoleic acid (18:2)

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

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

The presence of α-linolenic acid (18:3) is required, which is dehydrogenated (18:4), lengthened (20:4) and dehydrogenated again (20:5).

Regulation of fatty acid synthesis

The following regulators of fatty acid synthesis exist.

Acyl-S-CoA.

firstly, according to the principle of negative feedback, it inhibits the enzyme acetyl-S-CoA carboxylase, interfering with 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 – acetyl-S-CoA to malonyl-S-CoA.

Covalent modification-

tion acetyl-S-CoA carboxylase by phosphorylation-

dephosphorylation. Participate-

They are cAMP-dependent protein kinase and protein phosphatase. Insu-

lin activates protein

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

carboxylase. Glucagon And address-

nalin via the adenylate cyclase mechanism, they cause inhibition of the same enzyme and, consequently, of all lipogenesis.

SYNTHESIS OF TRIACYLGLYCEROLS AND PHOSPHOLIPIDS

General principles of biosynthesis

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

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

phosphatidic acid. It can be transformed in two ways - into TsDF-DAG or dephosphorylate to DAG. The latter, in turn, is either acylated to

TAG either 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 surfactant.

TsDF-DAG, being the active form of phosphatidic acid, is further converted 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 during

breakdown of CM, VLDL, HDL or synthesized in

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

dependent reaction.

Glycerolin the liver activated in the phosphorylation reaction using high-energy

ATP phosphate. IN muscles and adipose tissue this reaction

tion 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, it is synthesized phosphatidic acid.

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

If palmitic, stearic, palmitooleic, and oleic acids are used, then phosphatidic acid is sent for the synthesis of TAG,

In the presence of polyunsaturated fatty acids, phosphatidic acid is

precursor of phospholipids.

Synthesis of triacylglycerols

Biosynthesis of TAG liver increases when the following conditions are met:

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

increased 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.

Phospholipid synthesis

Biosynthesis of phospholipids Compared to the synthesis of TAG, it 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 following reaction, activated choline (or ethanolamine) is transferred to DAG

This pathway is typical for the lungs and intestines.

2. Activation phosphatidic acid is to join the CMF 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 infiltration

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 includes heterogeneous compounds, the block

can occur at different levels of synthesis.

Block of apoprotein synthesis - lack of protein or essential amino acids in food,

exposure to chloroform, arsenic, lead, CCl4;

phospholipid synthesis block – absence of lipotropic factors (vitamins,

methionine, polyunsaturated fatty acids);

block for the assembly of lipoprotein particles when exposed to chloroform, arsenic, lead, CCl4;

block of lipoprotein secretion into the blood - CCl4, active peroxidation

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

There may also be a deficiency of apoproteins and phospholipids with relative

excess substrate:

synthesis of increased amounts of TAG with excess fatty acids;

synthesis of increased amounts of cholesterol.

Obesity

Obesity is an excess amount of neutral fat in the subcutaneous fat

fiber.

There are two types of obesity – primary and secondary.

Primary obesity is a consequence of physical inactivity and overeating. In health

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 stimulates

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

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

Secondary obesity–occurs with hormonal diseases. Such problems

diseases include hypothyroidism, hypercortisolism.

A typical example of low pathogenic obesity is boron obesity.

sumo wrestlers. Despite the obvious excess weight, sumo masters retain their

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 genetic predisposition.

falsehood - 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 body's "desire" to prevent hyperglycemia. However, insulin resistance subsequently develops, since inevitable changes

Negative adipocytes 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.

Activation of lipolysis is also facilitated by the often observed imbalance between the consumption of saturated and polyunsaturated fatty acids, so

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

hydrolysis accelerates.

CHOLESTEROL METABOLISM

Cholesterol belongs to a group of compounds that have

based on a ring, and is an unsaturated alcohol.

Sources

Synthesis in the body is approximately 0.8 g/day,

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

intestines, the remaining part in any cells that have not lost their nucleus. Thus, all cells of the body are capable of synthesizing cholesterol.

Among food products, they are richest in cholesterol (calculated per 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 arrives on average 0,4 G.

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

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

to free cholesterol is 2:1.

Removal

The removal of cholesterol from the body occurs almost exclusively through the intestines:

with feces in the form of cholesterol and neutral sterols formed by 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 skin epithelium and sebaceous gland secretions,

approximately 0.1 g is converted into steroid hormones.

Function

Cholesterol is a 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

during the synthesis of fatty acids. Cholesterol biosynthesis requires 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.

Cholesterol synthesis.

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: insulin-

lin, by activating protein phosphatase, promotes

enzyme transition hydro-

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

state. Glucagon and ad-

renaline through the adenylate cyclase mechanism

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

it into an 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 blood level is 3.2-4.5 g/l

the most atherogenic

Function

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

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

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

some cells of loose connective tissue - fibroblasts, platelets,

endothelium, smooth muscle cells,

epithelium of the glomerular membrane of the kidneys,

bone marrow cells,

cornea cells,

neurocytes,

basophils of the adenohypophysis.

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

Cells that use LDL have a high-affinity receptor specific for LDL - apoB-100 receptor. When LDL interacts with the receptor,

There is endocytosis of lipoprotein and its lysosomal breakdown into its component parts - phospholipids, amino acids, glycerol, fatty acids, cholesterol and its esters.

CS is converted into hormones or incorporated into membranes. Excess membranes

high cholesterol is removed with the help of HDL.

Exchange

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

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

(about 50%).

High density lipoproteins

general characteristics

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

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 blood level is 0.5-1.5 g/l

antiatherogenic

Function

Transport of cholesterol from tissues to the liver

Donor of polyenoic acids for the synthesis of phospholipids and eicosanoids in cells

Exchange

The LCAT reaction actively occurs 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. HDL3, which loses its phospholipid membrane, 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 up part of the phospholipid shell, thus delivering polyene fatty acids to ordinary cells.

DISORDERS OF CHOLESTEROL METABOLISM

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 of increasing

actions):

abdominal aorta

coronary artery

popliteal artery

femoral artery

tibial artery

thoracic aorta

thoracic aortic arch

carotid arteries

Stages of atherosclerosis

Stage 1 – endothelial damage.This is the "pre-lipid" stage, found

even in one-year-old children. Changes at 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 adhesive are created in the endothelium.

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

telial clefts. This leads to increased release of lipoproteins (LDL and

VLDL) and monocytes into the intima.

Stage 2 – 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 and

contribute to the development of inflammation.

Lipoproteins in the inflammation zone are modified by oxidation, glycosylation

cation, acetylation.

Monocytes, transforming into macrophages, absorb altered lipoproteins with the participation of “garbage” receptors (scavenger receptors). The fundamental point is

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

the presence of apo B-100 receptors, which means NOT REGULATORY ! In addition to macrophages, in this way lipoproteins also enter smooth muscle cells, which massively re-

go into macrophage-like form.

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

roids and turn into foamy cells. Appear externally on the endothelium whether-

pigment spots and stripes.

Stage 3 – stage of late changes.It is characterized by the following special

benefits:

accumulation outside the cell of free cholesterol and esterified with linoleic acid

(that is, as in plasma);

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

encapsulation of cholesterol and formation of fibrous plaque.

Externally it appears as a protrusion of the surface into the lumen of the vessel.

Stage 4 – stage of complications.At this stage there is

plaque calcification;

plaque ulceration leading to lipid embolism;

thrombosis due to platelet adhesion and activation;

vessel rupture.

Treatment

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

Diet:

Fats in food should include equal proportions of saturated and 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 comes down to

limiting the absorption of cholesterol in the small intestine,

activation of bile acid synthesis,

decreased synthesis and secretion of LDL in the liver,

increasing HDL synthesis.

It has been established that if the ratio Polyunsaturated fatty acids is equal to 0.4, then

Saturated fatty acids

consumption of cholesterol in amounts up to 1.5 g per day does not lead to hypercholesterol

role-playing.

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

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

at the same time they themselves are not assimilated.

The sorption of cholesterol on fiber is comparable to that on special adsorbents.tah 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 into hepatocytes.

Suppression of cholesterol absorption 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 them

LDL in the blood

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

inhibit the catabolism of VLDL and chylomicrons, which increases the transfer 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 using 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 accompanied by

are fascinated by hyperlipidemia, so identifying dislipoproteinemia.

The causes of dyslipoproteinemia may be changes in enzyme activity

lipoprotein metabolism - LCAT or LPL, drug reception on cells, disruption of apoprotein synthesis.

There are several types of dislipoproteinemia.

TypeI: Hyperchylomicronemia.

Caused by genetic deficiency lipoprotein lipases.

Laboratory indicators:

increase in the number of chylomicrons;

normal or slightly increased levels of preβ-lipoproteins;

a sharp increase in TAG levels.

CS/TAG ratio< 0,15

Clinically manifested at an early age by xanthomatosis and hepatosplenomega

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

TypeII: Hyperβ - lipoproteinemia

How is fat formed in the human body?

The human body can form lipids or triglycerides not only from fats coming from food, but also from carbohydrates and proteins. Fats from incoming food enter the gastrointestinal tract, are absorbed in the small intestine, undergo a transformation process and are broken down into fatty acids and glycerol. There are also internal, endogenous fats that are synthesized in the liver. Fatty acids are a source of large amounts of energy, being a kind of body “fuel”.

They are absorbed into the blood and, with the help of special transport forms - lipoproteins, chylomicrons, are carried to various organs and tissues. Fatty acids can again be used for the synthesis of triglycerides and fat, and if they are in excess, they can be stored in the liver and in adipose tissue cells - adipocytes. It is adipocytes with a large supply of triglycerides that create discomfort for a person and are manifested by excess deposits of subcutaneous fat and excess weight. Fat deposits can also form from carbohydrates.

Glucose and fructose entering the blood with the help of the hormone insulin can be deposited in the form of triglycerides in the liver and cells. Proteins ingested from food can also be transformed into triglycerides through a cascade of transformations: proteins are broken down into amino acids, absorbed into the blood, penetrate into the liver, converted into glucose and, under the action of insulin, become triglycerides stored in adipocytes. This is a very simplified way to imagine the process of lipid formation in the human body.

2 Functions of lipids in the body

The role of fats in the human body is difficult to overestimate. They are:

• the main energy source in the body;
• building material for cell membranes, organelles, a number of hormones and enzymes;
• a protective “cushion” for internal organs.

Fat cells carry out thermoregulation, increase the body's resistance to infection, secrete hormone-like substances - cytokines, and also regulate metabolic processes.

3 How are fats used?

Triglycerides stored “in reserve” can leave adipocytes and be used for cell needs when they receive insufficient energy or require structural material to build membranes. Hormones of the body that have a lipolytic effect - adrenaline, glucagon, somatotropin, cortisol, thyroid hormones - send a signal to adipocytes - lipolysis or the process of fat breakdown occurs.

Having received “instructions” from hormones, triglycerides are broken down into fatty acids and glycerol. Fatty acids are transported into the blood using carriers called lipoproteins. Lipoproteins in the blood interact with cell receptors, which break down lipoproteins and take fatty acids for further oxidation and use: building membranes or producing energy. Lipolysis can be activated under stress and excessive physical activity.

4 Why is lipid metabolism disrupted?

Dyslipidemia or a disorder of lipid metabolism is a condition in which, for various reasons, there is a change in the content of lipids in the blood (increase or decrease), or the appearance of pathological lipoproteins. The condition is caused by pathological processes in the synthesis, breakdown of fats or their inadequate removal from the blood. Problems in lipid metabolism can lead to excess fat in the blood - hyperlipidemia.

According to research, this condition is typical for 40% of the adult population, and occurs even in childhood.

Disorders of lipid metabolism can be provoked by a number of factors that trigger pathological processes of imbalance in the supply and utilization of lipids. Risk factors include:

• physical inactivity or a sedentary lifestyle,
• smoking,
• alcohol abuse,
• increased activity of thyroid hormones,
• excess body weight,
• diseases that provoke lipid metabolic disorders.

5 Primary disorders of lipid metabolism

All lipid metabolism disorders are classified into primary and secondary. Primary ones are caused by genetic defects and are hereditary in nature. There are several forms of primary disorders in lipid metabolism, the most common being familial hypercholesterolemia. This condition is caused by a defect in the gene encoding the synthesis and function of receptors that bind to certain lipoproteins. There are several forms of pathology (homo- and heterozygous), they are united by the hereditary nature of the disease, high cholesterol levels from birth, early development of atherosclerosis and ischemic heart disease.

A doctor may suspect hereditary dyslipoproteinemia in a patient if:

• early myocardial infarction;
• significant damage to blood vessels by the atherosclerotic process at a young age;
• available data on the incidence of coronary artery disease and cardiovascular accidents in close relatives at a young age.

6 Secondary disorders of lipid metabolism

These lipid metabolism disorders develop as a consequence of many diseases, as well as as a result of the use of certain medications.

Causes of high blood lipids:

• diabetes,
• obesity,
• hypothyroidism,
• taking medications: progesterone, thiazides, estrogens, glucocorticoids,
• chronic renal failure,
• stress.

Reasons for low lipid levels:

• malabsorption syndrome,
• reduced, insufficient nutrition,
• tuberculosis,
• chronic liver diseases,
• AIDS.

Dyslipidemia of secondary origin is very often observed in type 2 diabetes mellitus. It is always accompanied by atherosclerosis - a change in the walls of blood vessels with the deposition of “plaques” of excess cholesterol and other lipid fractions on them. Among patients with diabetes, the most common cause of death is coronary artery disease caused by atherosclerotic disorders.

7 Consequences of high blood lipids

Excessively “fatty” blood is enemy number 1 for the body. Excessive amounts of lipid fractions, as well as defects in their utilization, inevitably lead to the fact that “all the excess” settles on the vascular wall with the formation of atherosclerotic plaques. Metabolic lipid disorders lead to the development of atherosclerosis, which means that in such patients the risk of developing coronary heart disease, stroke, and heart rhythm disturbances increases many times.

8 Signs indicating lipid metabolism disorders

An experienced physician may suspect dyslipidemia in a patient upon examination. External signs indicating existing advanced violations will be:

• multiple yellowish formations - xanthomas, located on the torso, abdomen, forehead skin, as well as xanthelasmas - yellow spots on the eyelids;
• Men may experience early graying of hair on the head and chest;
• matte ring around the edge of the iris.

All external signs are a relative indication of a lipid metabolism disorder, and to confirm it, a set of laboratory and instrumental studies is required to confirm the doctor’s assumptions.

9 Diagnosis of lipid metabolism disorders

There is an examination program to identify dyslipidemia, which includes:

• general blood test, urine test,
• BAC: determination of total cholesterol, TG, LDL cholesterol, VLDL, HDL, ASAT, ALAT, bilirubin, protein, protein fractions, urea, alkaline phosphatase,
• determining blood glucose, and if there is a tendency to increase, performing a glucose tolerance test,
• determination of abdominal circumference, Quetelet index,
• blood pressure measurement,
• Examination of the vessels of the fundus,
• EchoCG,
• radiography of the OGK.

This is a general list of studies, which in case of lipid metabolism disorders, at the discretion of the doctor, can be expanded and supplemented.

10 Treatment of lipid metabolism disorders

Therapy for secondary dyslipidemia is aimed, first of all, at eliminating the underlying disease that caused the disorder of lipid metabolism. Correction of glucose levels in diabetes mellitus, normalization of body weight in obesity, treatment of absorption disorders and in the gastrointestinal tract are guaranteed to improve lipid metabolism. Elimination of risk factors and a lipid-lowering diet for lipid metabolism disorders is the most important part on the path to recovery.

Patients should forget about smoking, stop drinking alcohol, lead an active lifestyle and combat physical inactivity. Food should be enriched with PUFAs (they contain liquid vegetable oils, fish, seafood), and the overall consumption of fats and foods containing saturated fats (butter, eggs, cream, animal fat) should be reduced. Drug therapy for lipid metabolism disorders includes taking statins, fibrates, nicotinic acid, and bile acid sequestrants according to indications.

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>> Digestion of fats, regulation of metabolism

Metabolism of fats (lipids) in the human body

Fat (lipid) metabolism in the human body consists of three stages

1. Digestion and absorption of fats in the stomach and intestines

2. Intermediate metabolism of fats in the body

3. Excretion of fats and their metabolic products from the body.

Fats are part of a large group of organic compounds - lipids, therefore the concepts of “fat metabolism” and “lipid metabolism” are synonymous.

An adult's body receives about 70 grams of fats of animal and plant origin per day. Fat breakdown does not occur in the oral cavity, since saliva does not contain the corresponding enzymes. Partial breakdown of fats into components (glycerol, fatty acids) begins in the stomach, but this process is slow for the following reasons:

1. in the gastric juice of an adult, the activity of the enzyme (lipase) for the breakdown of fats is very low,

2. the acid-base balance in the stomach is not optimal for the action of this enzyme,

3. in the stomach there are no conditions for emulsification (splitting into small droplets) of fats, and lipase actively breaks down fats only in the composition of a fat emulsion.

Therefore, in an adult, most of the fat passes through the stomach without significant changes.

Unlike adults, in children the breakdown of fats in the stomach occurs much more actively.

The main part of dietary lipids undergoes breakdown in the upper part of the small intestine, under the influence of pancreatic juice.

Successful breakdown of fats is possible if they first break down into small droplets. This occurs under the influence of bile acids entering the duodenum with bile. As a result of emulsification, the surface of fats sharply increases, which facilitates their interaction with lipase.

Absorption of fats and other lipids occurs in the small intestine. Together with the products of fat breakdown, fat-soluble acids (A, D, E, K) enter the body.

The synthesis of fats specific to a given organism occurs in the cells of the intestinal wall. Subsequently, the newly created fats enter the lymphatic system, and then into the blood. The maximum fat content in the blood plasma occurs between 4 and 6 hours after eating a fatty meal. After 10 - 12 hours, the fat concentration returns to normal.

The liver takes an active part in fat metabolism. In the liver, some of the newly formed fats are oxidized to form the energy necessary for the body’s functioning. The other part of the fats is converted into a form convenient for transportation and enters the blood. Thus, from 25 to 50 grams of fat are transferred per day. Fats that the body does not immediately use are carried through the bloodstream into fat cells, where they are stored as reserves. These compounds can be used during fasting, exercise, and so on.

Fats are an important source of energy for our body. During short-term and sudden loads, the energy of glycogen, which is located in the muscles, is first used. If the load on the body does not stop, then the breakdown of fats begins.

From here it is necessary to conclude that if you want to get rid of extra pounds through physical activity, it is necessary that these activities be long enough for at least 30 - 40 minutes.

Fat metabolism is very closely related to carbohydrate metabolism. With an excess of carbohydrates in the body, fat metabolism slows down, and work goes only in the direction of synthesizing new fats and storing them in reserve. If there is a lack of carbohydrates in food, on the contrary, the breakdown of fats from the fat reserve is activated. From this we can conclude that nutrition for weight loss should limit (within reasonable limits) not only the consumption of fats, but also carbohydrates.

Most of the fats we eat are used by our body or stored in reserve. Under normal conditions, only 5% of fats are excreted from our body, this is done with the help of the sebaceous and sweat glands.

Regulation of fat metabolism

Regulation of fat metabolism in the body occurs under the guidance of the central nervous system. Our emotions have a very strong influence on fat metabolism. Under the influence of various strong emotions, substances enter the bloodstream that activate or slow down fat metabolism in the body. For these reasons, one must eat in a calm state of consciousness.

Disorders of fat metabolism can occur with a regular lack of vitamins A and B in food.

The physicochemical properties of fat in the human body depend on the type of fat supplied with food. For example, if a person’s main source of fat is vegetable oils (corn, olive, sunflower), then the fat in the body will have a more liquid consistency. If animal fats (lamb, pork fat) predominate in human food, then fats more similar to animal fat (hard consistency with a high melting point) will be deposited in the body. There is experimental confirmation of this fact.

How to remove trans fatty acids from the body

One of the most important tasks that modern people face is how to cleanse their own body of toxins and poisons that have accumulated “thanks to” poor quality daily nutrition. A significant role in polluting the body is played by trans fats, which are abundantly supplied with daily food and over time greatly inhibit the functioning of internal organs.

Basically, trans fatty acids are eliminated from the body due to the ability of cells to renew. Some cells die and new ones appear in their place. If there are cells in the body whose membranes consist of trans-fatty acids, then after they die, new cells may appear in their place, the membranes of which consist of high-quality fatty acids. This happens if a person excludes foods containing trans fatty acids from the diet.

To ensure that as little trans fatty acids as possible penetrate cell membranes, you need to increase the amount of Omega-3 fatty acids you consume daily. By consuming foods containing such oils and fats, you can ensure that the membranes of nerve cells have the correct structure, which will have a positive effect on the functioning of the brain and nervous system.

We must remember that during heat treatment, fats can decompose to form irritating and harmful substances. Overheating fats reduces their nutritional and biological value.

Additional articles with useful information

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The lack of fats in food significantly undermines a person’s health, and if healthy fats are present in the diet, then a person’s life becomes much easier by increasing physical and mental performance.

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Obesity has recently become increasingly widespread among the world's population, and this disease requires long-term and systemic treatment.