Synthesis of lipids and carbohydrates in the cell
Lipidsare very important in cell metabolism. All lipids are organic water-insoluble compounds present in all living cells. It should be noted that, according to their functions, lipids are divided into three groups:
- structural and receptor lipids of cell membranes
- energetic "depot" of cells and organisms
- vitamins and hormones of the lipid group
Lipids are based on fatty acid(saturated and unsaturated) and organic alcohol - glycerol. We get the bulk of fatty acids from food (animal and vegetable). Animal fats - ϶ᴛᴏ a mixture of saturated (40-60%) and unsaturated (30-50%) fatty acids. Vegetable fats are the richest (75-90%) unsaturated fatty acids and the most beneficial for our body.
The bulk of fats is used for energy metabolism, being broken down by special enzymes - lipases and phospholipases... As a result, fatty acids and glycerol are obtained, which are further used in the reactions of glycolysis and the Krebs cycle. In terms of the formation of ATP molecules - fats form the basis of the energy reserve of animals and humans.
The eukaryotic cell receives fats from food, although it itself can synthesize most fatty acids ( except for two irreplaceable– linoleic and linolenic)... Synthesis begins in the cytoplasm of cells with the help of a complex complex of enzymes and ends in mitochondria or smooth endoplasmic reticulum.
The initial product for the synthesis of most lipids (fats, steroids, phospholipids) is a “universal” molecule - acetyl-Coenzyme A (activated acetic acid), which is an intermediate product of most catabolic reactions in the cell.
There are fats in any cell, but especially a lot of them in special fat cells - adipocytes forming adipose tissue. Fat metabolism in the body is controlled by special pituitary hormones, as well as insulin and adrenaline.
Carbohydrates(monosaccharides, disaccharides, polysaccharides) are the most important compounds for energy metabolism reactions. As a result of the breakdown of carbohydrates, the cell receives most of the energy and intermediates for the synthesis of other organic compounds (proteins, fats, nucleic acids).
The cell and the body receive the bulk of sugars from the outside - from food, but can synthesize glucose and glycogen from non-carbohydrate compounds. Substrates for various types of carbohydrate synthesis are molecules of lactic acid (lactate) and pyruvic acid (pyruvate), amino acids and glycerin. These reactions take place in the cytoplasm with the participation of a whole complex of enzymes - glucose phosphatases. All fusion reactions require energy - the fusion of 1 glucose molecule requires 6 ATP molecules!
The bulk of its own synthesis of glucose occurs in the cells of the liver and kidneys, but does not go to the heart, brain and muscles (there are no necessary enzymes there). For this reason, disorders of carbohydrate metabolism primarily affect the work of these organs. Carbohydrate metabolism is controlled by a group of hormones: pituitary hormones, glucocorticosteroid hormones of the adrenal glands, insulin and pancreatic glucagon. Disruption of the hormonal balance of carbohydrate metabolism leads to the development of diabetes.
We have briefly covered the main parts of plastic exchange. You can make a number general conclusions:
Synthesis of lipids and carbohydrates in a cell - concept and types. Classification and features of the category "Synthesis of lipids and carbohydrates in the cell" 2017, 2018.
If ever large amounts of carbohydrates enter the body, they are either immediately used for energy, or are stored in the form of glycogen, and their excess is quickly converted into triglycerides and stored in this form in adipose tissue. In humans, most triglycerides are formed in the liver, but very small amounts can also be formed in the adipose tissue itself. Triglycerides produced in the liver are transported mainly as very low density lipoproteins into adipose tissue, where they are stored.
Conversion of acetyl-CoA to fatty acids... The first step in triglyceride synthesis is the conversion of carbohydrates to acetyl-CoA.
This happens during normal cleavage glucose glycolytic system. Due to the fact that fatty acids are large polymers of acetic acid, it is easy to imagine how acetyl-CoA can be converted to fatty acid. However, the synthesis of fatty acids is not provided simply by reversing the direction of the oxidative cleavage reaction. This synthesis is carried out in a two-step process, shown in the figure, using malonyl-CoA and NADP-H as the main mediators of the polymerization process.
Combining fatty acids with a-glycerophosphate in the formation of triglycerides. As soon as the synthesized fatty acid chains begin to include from 14 to 18 carbon atoms, they interact with glycerol to form triglycerides. The enzymes that catalyze this reaction are highly specific for fatty acids with chain lengths of 14 carbon atoms and above, which is a factor that controls the structural alignment of triglycerides stored in the body.
Glycerol formation parts of a triglyceride molecule provided by a-glycerophosphate, which is a by-product of the glycolytic breakdown of glucose.
Efficiency of Converting Carbohydrates to Fat... During triglyceride synthesis, only 15% of the potential energy in glucose is lost as heat. The remaining 85% is converted into energy by stored triglycerides.
The Importance of Fat Synthesis and Storage... The synthesis of fats from carbohydrates is especially important for two reasons.
1. The ability of various cells organism to store carbohydrates in the form of glycogen is poorly expressed. Only a few hundred grams of glycogen can be stored in the liver, skeletal muscle, and all other body tissues combined. At the same time, kilograms of fat can be stored, so fat synthesis is a way in which the energy contained in excess carbohydrates (and proteins) ingested can be stored for later use. The amount of energy stored by the human body in the form of fat is approximately 150 times the amount of energy stored in the form of carbohydrates.
2. Each gram of fat contains almost 2.5 times more energy than each gram of carbohydrates. Consequently, with the same body weight, the body can store several times more energy in the form of fats than in the form of carbohydrates, which is especially important if a high degree of mobility is required in order to survive.
Decreased synthesis of fats from carbohydrates in the absence of insulin. In the absence of insulin, as is the case with severe diabetes mellitus, little, if any, fats are synthesized for the following reasons. First, in the absence of insulin, glucose cannot enter in any significant amounts into adipose tissues and liver cells, which does not ensure the formation of sufficient amounts of acetyl-CoA and NADP-H, which are necessary for the synthesis of fats and obtained during glucose metabolism. Secondly, the absence of glucose in fat cells significantly reduces the amount of glycerophosphate available, which also hinders the formation of triglycerides.
Fats are synthesized from glycerin and fatty acids.
Glycerin in the body occurs during the breakdown of fat (food and own), and is also easily formed from carbohydrates.
Fatty acids are synthesized from acetyl coenzyme A. Acetyl coenzyme A is a universal metabolite. Its synthesis requires hydrogen and ATP energy. Hydrogen is obtained from NADP.H2. The body synthesizes only saturated and monounsaturated (having one double bond) fatty acids. Fatty acids that have two or more double bonds in the molecule, called polyunsaturated, are not synthesized in the body and must be supplied with food. For the synthesis of fat, fatty acids can be used - products of hydrolysis of edible and own fats.
All participants in the synthesis of fat must be in an active form: glycerin in the form glycerophosphate, and fatty acids in the form acetyl coenzyme A. Fat synthesis is carried out in the cytoplasm of cells (mainly adipose tissue, liver, small intestine). The pathways of fat synthesis are presented in the scheme.
It should be noted that glycerol and fatty acids can be obtained from carbohydrates. Therefore, with excessive consumption of them against the background of a sedentary lifestyle, obesity develops.
DAP - dihydroacetone phosphate,
DAG - diacylglycerol.
TAG - triacylglycerol.
General characteristics of lipoproteins. Lipids in the aquatic environment (and therefore in the blood) are insoluble, therefore, lipid-protein complexes - lipoproteins - are formed in the body for the transport of lipids by the blood.
All types of lipoproteins have a similar structure - a hydrophobic core and a hydrophilic layer on the surface. The hydrophilic layer is formed by proteins called apoproteins and amphiphilic lipid molecules - phospholipids and cholesterol. The hydrophilic groups of these molecules face the aqueous phase, and the hydrophobic parts face the hydrophobic nucleus of the lipoprotein, which contains the transported lipids.
Apoproteins perform several functions:
Form the structure of lipoproteins;
They interact with receptors on the surface of cells and thus determine which tissues will capture this type of lipoproteins;
They serve as enzymes or activators of enzymes that act on lipoproteins.
Lipoproteins. The following types of lipoproteins are synthesized in the body: chylomicrons (HM), very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL) and high density lipoproteins (HDL). Each type of LP is formed in different tissues and transports certain lipids. For example, HMs transport exogenous (dietary fats) from the intestine to tissues, therefore triacylglycerols make up 85% of the mass of these particles.
Properties of lipoproteins. Medicinal products are readily soluble in blood, non-opalescent, since they have a small size and a negative charge.
surface. Some LPs easily pass through the capillary walls of blood vessels and deliver lipids to cells. The large size of the CM does not allow them to penetrate the walls of the capillaries, therefore, from the intestinal cells, they first enter the lymphatic system and then, through the main thoracic duct, enter the blood along with the lymph. The fate of fatty acids, glycerol and residual chylomicrons. As a result of the action of LP-lipase on HM fats, fatty acids and glycerol are formed. Most of the fatty acids penetrate into the tissues. In adipose tissue during the absorption period, fatty acids are deposited in the form of triacylglycerols, in the heart muscle and working skeletal muscles are used as a source of energy. Another product of fat hydrolysis, glycerol, is soluble in blood, transported to the liver, where during the absorption period it can be used for the synthesis of fats.
Hyperchylomicronemia, hypertriglycerolonemia. After eating food containing fats, physiological hypertriglyceronemia develops and, accordingly, hyperchylomicronemia, which can last up to several hours. The rate of HM removal from the bloodstream depends on:
LP-lipase activity;
The presence of HDL, supplying apoproteins C-II and E for XM;
Activity of transfer of apoC-II and apoE to XM.
Genetic defects in any of the proteins involved in HM metabolism lead to the development of familial hyperchylomicronemia - type I hyperlipoproteinemia.
In plants of the same species, the composition and properties of fat can fluctuate depending on the climatic conditions of growth. The content and quality of fats in animal raw materials also depends on the breed, age, body condition, gender, season of the year, etc.
Fats are widely used in the production of many food products; they have a high caloric value and nutritional value, and cause a long-lasting feeling of satiety. Fats are important flavoring and structural components in food preparation and have a significant impact on the appearance of food. When frying, fat acts as a heat transfer medium.
|
The product's name |
The product's name |
Approximate fat content in food products,% on wet weight |
|
|
Rye bread | |||
|
Sunflower |
Fresh vegetables | ||
|
Fresh fruits | |||
|
Beef | |||
|
Cocoa beans | |||
|
Peanut nuts |
Mutton | ||
|
Walnuts (kernels) |
A fish | ||
|
Cereals: |
Cow's milk | ||
|
Butter | |||
|
Margarine | |||
Fats obtained from plant and animal tissues, in addition to glycerides, may contain free fatty acids, phosphatides, sterols, pigments, vitamins, flavoring and aromatic substances, enzymes, proteins, etc., which affect the quality and properties of fats. The taste and smell of fats is also influenced by substances formed in fats during storage (aldehydes, ketones, peroxides and other compounds).
Fats in the human body must constantly be supplied with food. The need for fats depends on age, nature of work, climatic conditions and other factors, but on average, an adult needs from 80 to 100 g of fat per day. The daily diet should contain approximately 70% animal and 30% vegetable fats.
In adipose tissue, for the synthesis of fats, mainly fatty acids are used, released during the hydrolysis of fats by CM and VLDL. Fatty acids enter adipocytes, are converted into CoA derivatives and interact with glycerol-3-phosphate, forming first lysophosphatidic acid and then phosphatidic acid. After dephosphorylation, phosphatidic acid is converted to diacylglycerol, which is acylated to form triacylglycerol.
In addition to fatty acids entering adipocytes from the blood, these cells also synthesize fatty acids from the breakdown products of glucose. In adipocytes, to ensure the reactions of fat synthesis, the breakdown of glucose occurs in two ways: glycolysis, which ensures 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 the reactions of fatty acid synthesis.
The fat molecules in adipocytes are combined into large fat droplets that do not contain water, and therefore are the most compact form of storage of fuel molecules. It is estimated 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. 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 the synthesis of fats, interacting with glycerol-3-phosphate. As in adipose tissue, fat synthesis occurs through the formation of phosphatidic acid. Fats synthesized in the liver are packed in VLDL and secreted into the blood
| Types of lipoproteins | Chylomicrons (HM) | VLDL | LDPP | LDL | HDL |
| Compound, % | |||||
| Squirrels | |||||
| FL | |||||
| XC | |||||
| EHS | |||||
| TAG | |||||
| Functions | Transport of lipids from intestinal cells (exogenous lipids) | Transport of lipids synthesized in the liver (endogenous lipids) | An intermediate form of the conversion of VLDL to LDL under the action of the enzyme LP-lipase | Transport of cholesterol in tissue | Removal of excess cholesterol from cells and other lipoproteins. Donor of apoproteins A, C-P |
| Place of education | Small intestine epithelium | Liver cells | Blood | Blood (from VLDL and IDL) | Liver cells - HDL precursors |
| Density, g / ml | 0,92-0,98 | 0,96-1,00 | 1,00-1,06 | 1,06-1,21 | |
| Particle diameter, nm | More than 120 | 30-100 | 21-100 | 7-15 | |
| Essential apolipoproteins | B-48 C-P E | B-100 C-P E | B-100 E | B-100 | A-I C-II E |
The composition of VLDL, in addition to fats, includes cholesterol, phospholipids and a protein - apoB-100. It is a very "long" protein containing 11,536 amino acids. One apoB-100 molecule covers the surface of all lipoprotein.
VLDL from the liver are secreted into the blood, where LP-lipase acts on them, as well as on HM. Fatty acids enter tissues, in particular adipocytes, and are used for the synthesis of fats. In the process of removing fats from VLDL under the action of LP-lipase, VLDL is first converted into LDL, and then into LDL. In LDL, the main lipid components are cholesterol and its esters, therefore LDL are lipoproteins that deliver cholesterol to peripheral tissues. Glycerol, released from lipoproteins, is transported by blood to the liver, where it can again be used for the synthesis of fats.
51. Regulation of blood glucose.
Concentration of glucose in arterial blood during the day is maintained at a constant level of 60-100 mg / dL (3.3-5.5 mmol / L). After consuming a carbohydrate meal, the glucose level rises over about 1 hour to 150 mg / dL
Rice. 7-58. Synthesis of fat from carbohydrates. 1 - oxidation of glucose to pyruvate and oxidative decarboxylation of pyruvate lead to the formation of acetyl-CoA; 2 - acetyl-CoA is a building block for fatty acid synthesis; 3 - fatty acids and a-glycerol phosphate, formed in the reduction reaction of dihydroxyacetone phosphate, are involved in the synthesis of triacylglycerols.
(∼8 mmol / L, nutritional hyperglycemia) and then returns to normal (after about 2 hours). Figure 7-59 shows a graph of changes in blood glucose concentration during the day with three meals a day.
Rice. 7-59. Change in blood glucose concentration during the day. A, B - the period of digestion; C, D - post-absorption period. The arrow indicates the time of food intake, the dotted line shows the normal glucose concentration.
A. Regulation of blood glucose in the absorptive and postabsorptive periods
To prevent an excessive increase in the concentration of glucose in the blood during digestion, the consumption of glucose by the liver and muscles, to a lesser extent - by adipose tissue, is of primary importance. It should be recalled that more than half of all glucose (60%) entering the portal vein from the intestine is absorbed by the liver. About 2/3 of this amount is deposited in the liver in the form of glycogen, the rest is converted into fats and oxidized, providing the synthesis of ATP. The acceleration of these processes is initiated by an increase in the insulatinglucagon index. Another part of the glucose from the intestines goes into the general bloodstream. Approximately 2/3 of this amount is absorbed by muscle and adipose tissue. This is due to an increase in the permeability of the membranes of muscle and fat cells for glucose under the influence of a high concentration of insulin. Glucose in muscles is deposited in the form of glycogen, and in fat cells it is converted to fat. The rest of the glucose in the general blood flow is absorbed by other cells (non-insulin dependent).
With a normal diet and a balanced diet, the concentration of glucose in the blood and the supply of glucose to all organs is maintained mainly due to the synthesis and breakdown of glycogen. Only towards the end of the night's sleep, i.e. by the end of the longest break between meals, the role of gluconeogenesis may increase slightly, the value of which will increase if breakfast does not take place and fasting continues (Fig. 7-60).
Rice. 7-60. Sources of glucose in the blood during digestion and during fasting. 1 - during the period of digestion, food carbohydrates are the main source of glucose in the blood; 2 - in the post-absorptive period, the liver supplies glucose to the blood due to the processes of glycogenolysis and gluconeogenesis, and for 8-12 hours the level of glucose in the blood is maintained mainly due to the breakdown of glycogen; 3 - gluconeogenesis and glycogen in the liver are equally involved in maintaining normal glucose concentrations; 4 - during the day, liver glycogen is almost completely depleted, and the rate of gluconeogenesis increases; 5 - with prolonged fasting (1 week or more), the rate of gluconeogenesis decreases, but gluconeogenesis remains the only source of glucose in the blood.
B. Regulation of blood glucose during extreme fasting
During fasting during the first day, the reserves of glycogen in the body are depleted, and in the future, only gluconeogenesis (from lactate, glycerol and amino acids) serves as a source of glucose. In this case, gluconeogenesis is accelerated, and glycolysis is slowed down due to the low concentration of insulin and high concentration of glucagon (the mechanism of this phenomenon was described earlier). But, in addition, after 1–2 days, the effect of another regulation mechanism - induction and repression of the synthesis of some enzymes - is significantly manifested: the amount of glycolytic enzymes decreases and, conversely, the amount of gluconeogenesis enzymes increases. Changes in enzyme synthesis are also associated with the influence of insulin and glucagon (the mechanism of action is discussed in section 11).
Starting from the second day of fasting, the maximum rate of gluconeogenesis from amino acids and glycerol is reached. The rate of gluconeogenesis from lactate remains constant. As a result, about 100 g of glucose is synthesized daily, mainly in the liver.
It should be noted that during fasting, glucose is not used by muscle and fat cells, since in the absence of insulin it does not penetrate into them and thus is saved to supply the brain and other glucose-dependent cells. Since under other conditions muscles are one of the main consumers of glucose, stopping the consumption of glucose by muscles during fasting is essential for supplying glucose to the brain. With a sufficiently prolonged fast (several days or more), the brain begins to use other sources of energy (see section 8).
A variant of fasting is an unbalanced diet, in particular, when the diet contains few carbohydrates in calories - carbohydrate starvation. In this case, gluconeogenesis is also activated, and amino acids and glycerol, formed from dietary proteins and fats, are used for glucose synthesis.
B. Regulation of blood glucose during rest and during exercise
Both during rest and during prolonged physical work, first the glycogen stored in the muscles themselves serves as a source of glucose for the muscles, and then blood glucose. It is known that 100 g of glycogen is consumed for running for about 15 minutes, and the glycogen stores in muscles after ingestion of carbohydrate food can be 200-300 g. duration. The regulation of glycogen mobilization in muscles and liver, as well as gluconeogenesis in the liver, has been described previously (chapters VII, X).
Rice. 7-61. Contribution of liver glycogen and gluconeogenesis to the maintenance of blood glucose levels during rest and during prolonged exercise. The dark part of the bar is the contribution of liver glycogen to maintaining blood glucose levels; light - the contribution of gluconeogenesis. With an increase in the duration of physical activity from 40 minutes (2) to 210 minutes (3), the breakdown of glycogen and gluconeogenesis almost equally provide blood with glucose. 1 - a state of rest (post-absorptive period); 2,3 - physical activity.
So, the information presented allows us to conclude that the coordination of the rates of glycolysis, gluconeogenesis, synthesis and decomposition of glycogen with the participation of hormones provides:
- preventing an excessive increase in blood glucose concentration after a meal;
- storing glycogen and using it between meals;
- the supply of glucose to the muscles, the need for which for energy rapidly increases during muscle work;
- the supply of glucose to cells that, during fasting, use mainly glucose as a source of energy (nerve cells, erythrocytes, renal medulla, testes).
52. Insulin. Structure, formation from proinsulin. Change in concentration depending on the diet.
Insulin- a protein hormone, synthesized and secreted into the blood by the p-cells of the islets of Langerhans of the pancreas, β-cells are sensitive to changes in blood glucose and secrete insulin in response to an increase in its content after eating. The transport protein (GLUT-2), which ensures the entry of glucose into β-cells, has a low affinity for it. Consequently, this protein transports glucose into the pancreatic cell only after its content in the blood is above the normal level (more than 5.5 mmol / l).
In β-cells, glucose is phosphorylated by glucokinase, which also has a high K m for glucose - 12 mmol / L. The rate of phosphorylation of glucose by glucokinase in β-cells is directly proportional to its concentration in the blood.
Insulin synthesis is regulated by glucose. Glucose (or its metabolites) appears to be directly involved in the regulation of insulin gene expression. The secretion of insulin and glucagon is also regulated by glucose, which stimulates the secretion of insulin from β-cells and suppresses the secretion of glucagon from α-cells. In addition, insulin itself decreases glucagon secretion (see section 11).
The synthesis and release of insulin is a complex process that includes several stages. Initially, an inactive hormone precursor is formed, which, after a series of chemical transformations during maturation, turns into an active form. Insulin is produced throughout the day, not just at night.
The gene encoding the primary structure of the insulin precursor is located on the short arm of chromosome 11.
On the ribosomes of the rough endoplasmic reticulum, a precursor peptide is synthesized - the so-called. preproinsulin. It is a polypeptide chain built of 110 amino acid residues and includes in series: L-peptide, B-peptide, C-peptide and A-peptide.
Almost immediately after synthesis in the EPR, a signal (L) peptide is cleaved from this molecule - a sequence of 24 amino acids, which are necessary for the passage of the synthesized molecule through the hydrophobic lipid membrane of the EPR. Proinsulin is formed, which is transported to the Golgi complex, then in the tanks of which the so-called maturation of insulin takes place.
Maturation is the longest stage in insulin production. During maturation, a C-peptide, a fragment of 31 amino acids connecting the B-chain and the A-chain, is excised from the proinsulin molecule using specific endopeptidases. That is, the proinsulin molecule is separated into insulin and a biologically inert peptide residue.
In secretory granules, insulin combines with zinc ions to form crystalline hexameric aggregates .
53. The role of insulin in the regulation of the metabolism of carbohydrates, lipids and amino acids.
One way or another, insulin affects all types of metabolism throughout the body. However, first of all, the effect of insulin concerns precisely the metabolism of carbohydrates. The main effect of insulin on carbohydrate metabolism is associated with increased glucose transport across cell membranes. Activation of the insulin receptor triggers an intracellular mechanism that directly affects the flow of glucose into the cell by regulating the amount and function of membrane proteins that carry glucose into the cell.
The transport of glucose in two types of tissues depends to the greatest extent on insulin: muscle tissue (myocytes) and adipose tissue (adipocytes) - this is the so-called. insulin-dependent tissues. Composing together almost 2/3 of the entire cellular mass of the human body, they perform such important functions in the body as movement, respiration, blood circulation, etc., and store the energy released from food.
Mechanism of action
Like other hormones, insulin acts through a receptor protein.
The insulin receptor is a complex integral protein of the cell membrane, built of 2 subunits (a and b), each of which is formed by two polypeptide chains.
Insulin binds with high specificity and is recognized by the a-subunit of the receptor, which, when a hormone is attached, changes its conformation. This leads to the appearance of tyrosine kinase activity in the b subunit, which triggers a branched chain of reactions for enzyme activation, which begins with receptor autophosphorylation.
The whole complex of biochemical consequences of the interaction of insulin and the receptor is not yet completely clear, however, it is known that at the intermediate stage, the formation of secondary mediators occurs: diacylglycerols and inositol triphosphate, one of the effects of which is the activation of the enzyme, protein kinase C, with a phosphorylating (and activating) action of which on enzymes and changes in intracellular metabolism are associated.
An increase in the flow of glucose into the cell is associated with the activating effect of insulin mediators on the incorporation into the cell membrane of cytoplasmic vesicles containing the glucose transporter GLUT 4.
Physiological effects of insulin
Insulin has a complex and multifaceted effect on metabolism and energy. Many of the effects of insulin are realized through its ability to act on the activity of a number of enzymes.
Insulin is the only hormone that lowers blood glucose, this is realized through:
increased absorption of glucose and other substances by cells;
activation of key glycolysis enzymes;
an increase in the intensity of glycogen synthesis - insulin accelerates the storage of glucose by liver and muscle cells by polymerizing it into glycogen;
a decrease in the intensity of gluconeogenesis - the formation of glucose in the liver from various substances decreases
Anabolic effects
enhances the absorption of amino acids by cells (especially leucine and valine);
enhances the transport of potassium ions into the cell, as well as magnesium and phosphate;
enhances DNA replication and protein biosynthesis;
enhances the synthesis of fatty acids and their subsequent esterification - in adipose tissue and in the liver, insulin promotes the conversion of glucose into triglycerides; with a lack of insulin, the opposite occurs - the mobilization of fats.
Anti-catabolic effects
inhibits protein hydrolysis - reduces protein degradation;
reduces lipolysis - reduces the flow of fatty acids into the blood.
54. Diabetes mellitus. The most important changes in hormonal status and metabolism. 55. Pathogenesis of the main symptoms of diabetes mellitus.
Diabetes. Insulin plays an important role in the regulation of glycolysis and gluconeogenesis. If the insulin content is insufficient, a disease occurs, which is called "diabetes mellitus": the concentration of glucose in the blood increases (hyperglycemia), glucose appears in the urine (glucosuria) and the glycogen content in the liver decreases. In this case, muscle tissue loses its ability to utilize blood glucose. In the liver, with a general decrease in the intensity of biosynthetic processes: biosynthesis of proteins, synthesis of fatty acids from the breakdown products of glucose, an increased synthesis of gluconeogenesis enzymes is observed. When insulin is administered to diabetic patients, metabolic changes are corrected: the permeability of membrane muscle cells for glucose is normalized, and the relationship between glycolysis and gluconeogenesis is restored. Insulin controls these processes at the genetic level as an inducer of the synthesis of key glycolysis enzymes: hexokinase, phosphofructokinase and pyruvate kinase. Insulin also induces glycogen synthase synthesis. At the same time, insulin acts as a repressor of the synthesis of key gluconeogenesis enzymes. It should be noted that glucocorticoids serve as inducers of the synthesis of gluconeogenesis enzymes. In this regard, with insular insufficiency and maintaining or even increasing the secretion of corticosteroids (in particular, in diabetes), the elimination of the effect of insulin leads to a sharp increase in the synthesis and concentration of glucon enzymes.
There are two main points in the pathogenesis of diabetes mellitus:
1) insufficient production of insulin by the endocrine cells of the pancreas,
2) a violation of the interaction of insulin with the cells of the tissues of the body (insulin resistance) as a result of a change in the structure or a decrease in the number of specific receptors for insulin, a change in the structure of insulin itself or a violation of the intracellular mechanisms of signal transmission from the receptors of the organelle cells.
There is a hereditary predisposition to diabetes mellitus. If one of the parents is sick, then the probability of inheriting type 1 diabetes is 10%, and type 2 diabetes is 80%.
Pancreatic insufficiency (type 1 diabetes) The first type of disorder is characteristic of type 1 diabetes (the old name is insulin-dependent diabetes). The starting point in the development of this type of diabetes is the massive destruction of the endocrine cells of the pancreas (islets of Langerhans) and, as a result, a critical decrease in the level of insulin in the blood. Mass death of pancreatic endocrine cells can occur in the case of viral infections, cancer, pancreatitis, toxic lesions of the pancreas, stress conditions, various autoimmune diseases in which the cells of the immune system produce antibodies against β-cells of the pancreas, destroying them. This type of diabetes, in the overwhelming majority of cases, is typical for children and young people (up to 40 years old). In humans, this disease is often genetically determined and caused by defects in a number of genes located on the 6th chromosome. These defects form a predisposition to the body's autoimmune aggression against the cells of the pancreas and negatively affect the regenerative capacity of β-cells. Autoimmune damage to cells is based on their damage by any cytotoxic agents. This damage causes the release of autoantigens, which stimulate the activity of macrophages and T-killers, which in turn leads to the formation and release of interleukins into the blood in concentrations that have a toxic effect on pancreatic cells. Also, cells are damaged by macrophages located in the tissues of the gland. Prolonged hypoxia of pancreatic cells and a high-carbohydrate, fat-rich and protein-poor diet can also be provoking factors, which leads to a decrease in the secretory activity of islet cells and, in the long term, to their death. After the start of massive cell death, the mechanism of their autoimmune damage is triggered.
Extrapancreatic insufficiency (type 2 diabetes). Type 2 diabetes (the old name is non-insulin dependent diabetes) is characterized by the disorders indicated in point 2 (see above). In this type of diabetes, insulin is produced in normal or even increased amounts, but the mechanism of interaction of insulin with the cells of the body is disrupted (insulin resistance). The main cause of insulin resistance is dysfunction of membrane insulin receptors in obesity (the main risk factor, 80% of diabetic patients are overweight) - the receptors become unable to interact with the hormone due to changes in their structure or quantity. Also, in some types of type 2 diabetes, the structure of insulin itself may be disrupted (genetic defects). Along with obesity, old age, bad habits, arterial hypertension, chronic overeating, a sedentary lifestyle are also risk factors for type 2 diabetes. Overall, this type of diabetes most commonly affects people over 40. A genetic predisposition to type 2 diabetes has been proven, as indicated by 100% coincidence of the presence of the disease in homozygous twins. In type 2 diabetes mellitus, there is often a violation of the circadian rhythms of insulin synthesis and a relatively long absence of morphological changes in the tissues of the pancreas. The disease is based on the acceleration of insulin inactivation or the specific destruction of insulin receptors on the membranes of insulin-dependent cells. Acceleration of insulin destruction often occurs in the presence of portocaval anastomoses and, as a result, a rapid flow of insulin from the pancreas to the liver, where it is rapidly destroyed. The destruction of insulin receptors is a consequence of an autoimmune process, when autoantibodies perceive insulin receptors as antigens and destroy them, which leads to a significant decrease in the insulin sensitivity of insulin-dependent cells. The effectiveness of insulin at the same concentration in the blood becomes insufficient to ensure adequate carbohydrate metabolism.
As a result, primary and secondary disorders develop.
Primary.
Slowing down glycogen synthesis
Slowing down the rate of gluconidase reaction
Acceleration of gluconeogenesis in the liver
Glucosuria
Hyperglycemia
Secondary
Decreased glucose tolerance
Slow down protein synthesis
Slowing down the synthesis of fatty acids
Accelerating the release of protein and fatty acids from the depot
The phase of rapid insulin secretion in β-cells is disrupted during hyperglycemia.
As a result of disturbances in carbohydrate metabolism in the cells of the pancreas, the mechanism of exocytosis is disturbed, which, in turn, leads to aggravation of disturbances in carbohydrate metabolism. Following disorders of carbohydrate metabolism, disorders of fat and protein metabolism naturally begin to develop. Regardless of the mechanisms of development, a common feature of all types of diabetes is a persistent increase in blood glucose levels and impaired metabolism of body tissues that are no longer able to absorb glucose.
The inability of tissues to use glucose leads to increased catabolism of fats and proteins with the development of ketoacidosis.
An increase in the concentration of glucose in the blood leads to an increase in the osmotic pressure of the blood, which leads to a serious loss of water and electrolytes in the urine.
A persistent increase in the concentration of glucose in the blood negatively affects the state of many organs and tissues, which ultimately leads to the development of severe complications such as diabetic nephropathy, neuropathy, ophthalmopathy, micro- and macroangiopathy, various types of diabetic comas and others.
In diabetic patients, there is a decrease in the reactivity of the immune system and a severe course of infectious diseases.
Diabetes mellitus, like, for example, hypertension, is a genetically, pathophysiologically, clinically heterogeneous disease.
56. Biochemical mechanism of development of diabetic coma. 57. Pathogenesis of late complications of diabetes mellitus (micro- and macroangiopathy, retinopathy, nephropathy, cataract).
Late complications of diabetes mellitus are a group of complications, the development of which takes months, and in most cases years, of the course of the disease.
Diabetic retinopathy - damage to the retina in the form of microaneurysms, punctate and spotted hemorrhages, solid exudates, edema, and the formation of new vessels. Ends with hemorrhages in the fundus, can lead to retinal detachment. The initial stages of retinopathy are determined in 25% of patients with newly diagnosed type 2 diabetes mellitus. The incidence of retinopathy increases by 8% per year, so that after 8 years from the onset of the disease, retinopathy is detected in 50% of all patients, and after 20 years in approximately 100% of patients. It is more common in type 2, the degree of its severity correlates with the severity of neuropathy. The main cause of blindness in middle-aged and elderly people.
Diabetic micro- and macroangiopathy is a violation of vascular permeability, an increase in their fragility, a tendency to thrombosis and the development of atherosclerosis (occurs early, mainly small vessels are affected).
Diabetic polyneuropathy is most often in the form of glove-and-stocking bilateral peripheral neuropathy that begins in the lower extremities. Loss of pain and temperature sensitivity is the most important factor in the development of neuropathic ulcers and joint dislocations. Symptoms of peripheral neuropathy are numbness, burning sensation, or paresthesia beginning in the distal regions of the limb. An increase in symptoms at night is characteristic. Loss of sensation leads to easily occurring injuries.
Diabetic nephropathy - kidney damage, first in the form of microalbuminuria (excretion of albumin protein in the urine), then proteinuria. Leads to the development of chronic renal failure.
Diabetic arthropathy - joint pain, "crunching", restriction of mobility, a decrease in the amount of synovial fluid and an increase in its viscosity.
Diabetic ophthalmopathy - early development of cataracts (lens opacity), retinopathy (retinal damage).
Diabetic encephalopathy - changes in the psyche and mood, emotional lability or depression.
Diabetic foot - lesion of the feet of a patient with diabetes mellitus in the form of purulent-necrotic processes, ulcers and osteoarticular lesions, which occurs against the background of changes in peripheral nerves, blood vessels, skin and soft tissues, bones and joints. It is the main cause of amputation in patients with diabetes mellitus.
Diabetic coma is a condition that develops due to a lack of insulin in the body in patients with diabetes mellitus.
Hypoglycemic coma - from a lack of sugar in the blood - Hypoglycemic coma develops when the blood sugar level drops below 2.8 mmol / l, which is accompanied by excitement of the sympathetic nervous system and dysfunction of the central nervous system. With hypoglycemia, coma develops sharply, the patient feels chills, hunger, tremors in the body, loses consciousness, and occasionally there are short-lived convulsions. With a loss of consciousness, profuse sweating is noted: the patient is wet, "at least squeeze out", the sweat is cold.
Hyperglycemic coma - from excess blood sugar - hyperglycemic coma develops gradually, over the course of a day or more, accompanied by dry mouth, the patient drinks a lot, if at this moment blood is taken for a sugar test; then the indicators are increased (normally 3.3-5.5 mmol / l) 2-3 times. Its appearance is preceded by malaise, loss of appetite, headache, constipation or diarrhea, nausea, sometimes abdominal pain, occasionally vomiting. If, in the initial period of development of a diabetic coma, treatment is not promptly started, the patient goes into a state of prostration (indifference, forgetfulness, drowsiness); his consciousness is darkened. A distinctive feature of coma is that in addition to complete loss of consciousness, the skin is dry, warm to the touch, the smell of apples or acetone from the mouth, weak pulse, low blood pressure. Body temperature is normal or slightly elevated. The eyeballs are soft to the touch.
Energy is generated through the oxidation of fats and carbohydrates. However, an excessive amount of them leads to obesity, and a lack of glucose leads to poisoning of the body.
For the normal functioning of any organism, energy must be in sufficient quantities. Its main source is glucose. However, carbohydrates do not always fully compensate for energy needs, therefore lipid synthesis is important - a process that provides the cell with energy, with a low concentration of sugars.
Fats and carbohydrates are also the backbone for many cells and components for the processes that ensure the normal functioning of the body. Their sources are food components. In the form of glycogen, glucose is stored, and its excess amount is converted into fats, which are contained in adipocytes. With a large intake of carbohydrates, an increase in fatty acids occurs at the expense of foods that are consumed daily.
The synthesis process cannot begin immediately after the entry of fats into the stomach or intestines. This requires a suction process that has its own characteristics. Not all 100% of dietary fat ends up in the bloodstream. Of these, 2% is excreted unchanged by the intestines. This is due to both the food itself and the absorption process.
Fats from food cannot be used by the body without additional breakdown to alcohol (glycerin) and acids. Emulsification occurs in the duodenum with the obligatory participation of enzymes of the intestinal wall itself and the endocrine glands. Equally important is bile, which activates phospholipases. Already after splitting alcohol, fatty acids enter the bloodstream. The biochemistry of processes cannot be simple, as it depends on many factors.
Fatty acid
They are all divided into:
- short (the number of carbon atoms does not exceed 10);
- long (carbon is more than 10).
The short ones do not need additional compounds and substances to get into the bloodstream. While long fatty acids must necessarily form a complex with bile acids.
Short fatty acids and their ability to be absorbed quickly without additional compounds are important for babies whose intestines do not yet function as in adults. In addition, breast milk itself contains only short chains.
The resulting compounds of fatty acids with bile are called micelles. They have a hydrophobic core, insoluble in water and consisting of fats, and a hydrophilic membrane (soluble by bile acids). It is bile acids that allow lipids to be transported to adipocytes.
The micelle breaks down on the surface of the enterocytes and the blood is saturated with pure fatty acids, which soon end up in the liver. Chylomicrons and lipoproteins are formed in enterocytes. These substances are compounds of fatty acids, protein, and it is they that deliver useful substances to any cell.
Bile acids are not secreted by the intestines. A small part passes through the enterocytes and enters the bloodstream, while the larger part moves to the end of the small intestine and is absorbed through active transport.
Chylomicron composition: 
- triglycerides;
- cholesterol esters;
- phospholipids;
- free cholesterol;
- protein.
Chylomicrons, which are formed inside intestinal cells, are still young, large in size, and therefore cannot be in the blood on their own. They are transported to the lymphatic system and only after passing through the main duct enter the bloodstream. There they interact with high density lipoproteins and form the proteins apo-C and apo-E.
Only after these transformations can the chylomicrons be called mature, since they are used for the needs of the organism. The main task is to transport lipids to tissues that store or use them. These include adipose tissue, lungs, heart, kidneys.
Chylomicrons appear after a meal, therefore, the process of synthesis and transport of fat is activated only after a meal. Some tissues cannot absorb these complexes in their pure form, therefore part of it binds to albumin and only after that is consumed by the tissue. An example is skeletal tissue.
The enzyme lipoprotein lipase reduces triglycerides in chylomicrons, which is why they decrease and become residual. It is they that completely enter the hepatocytes and there the process of their cleavage to its constituent components ends.
The biochemistry of endogenous fat synthesis occurs with the use of insulin. Its amount depends on the concentration of carbohydrates in the blood, so sugar is needed for fatty acids to enter the cell.
Lipid resynthesis
Lipid resynthesis is the process by which lipids are synthesized in the wall, intestinal cell, from fats that enter the body with food. As a supplement, fats that are produced internally can also be involved.
This process is one of the most important, as it allows you to bind long fatty acids and prevent their destructive effect on membranes. Most often, endogenous fatty acids bind to an alcohol such as glycerol or cholesterol.
The resynthesis process does not end with binding. Next, there is packaging in forms that are able to leave the enterocyte, the so-called transport. It is in the intestine itself that two types of lipoproteins are formed. These include chylomicrons, which are not constant in the blood and their appearance depends on food intake, and high density lipoproteins, which are permanent forms, and their concentration should not exceed 2 g / l.
Use of fats
Unfortunately, the use of triglycerides (fats) for energy supply of the body is considered very laborious, therefore this process is considered a reserve process, even though it is much more efficient than obtaining energy from carbohydrates. 
Lipids for energy supply of the body are used only if there is an insufficient amount of glucose. This happens when there is a long absence of food intake, after an active load or after a long night's sleep. After fat oxidation, energy is obtained.
But since the body does not need all the energy, it has to accumulate. It accumulates in the form of ATP. It is this molecule that is used by cells for many reactions that proceed only with the expenditure of energy. The advantage of ATP is that it is suitable for all cellular structures of the body. If glucose is contained in sufficient volume, then 70% of the energy is absorbed by the oxidative processes of glucose and only the remaining percent is absorbed by the oxidation of fatty acids. With a decrease in the accumulated carbohydrate in the body, the advantage goes to the oxidation of fats.
So that the amount of incoming substances is not more than the output, this requires consumed fats and carbohydrates within the normal range. The average person needs 100 g of fat per day. This is justified by the fact that only 300 mg can be absorbed from the intestines into the blood. More will be withdrawn almost unchanged.
It is important to remember that lipid oxidation is impossible with a lack of glucose. This will lead to the fact that oxidation products - acetone and its derivatives - will accumulate in the cell in excess. Exceeding the norm gradually poisons the body, adversely affects the nervous system and, in the absence of help, can be fatal.
The biosynthesis of fats is an integral part of the functioning of the body. It is a reserve source of energy, which, in the absence of glucose, maintains all biochemical processes at the proper level. The transport of fatty acids to cells is carried out by chylomicrons and lipoproteins. A special feature is that chylomicrons appear only after a meal, and lipoproteins are constantly present in the blood.
Lipid biosynthesis is a process that depends on many additional processes. The presence of glucose must be mandatory, since the accumulation of acetone due to incomplete oxidation of lipids can lead to gradual poisoning of the body.
Loading ...