Carbohydrate metabolism

Carbohydrates are the main source of energy: 1 g of carbohydrates, when completely broken down, releases 16.7 kJ (4 kcal). In addition, carbohydrates in the form of mucopolysaccharides are part of connective tissue, and in the form of complex compounds (glycoproteins, lipopolysaccharides) are structural elements of cells, as well as components of some active biological substances (enzymes, hormones, immune bodies, etc.).

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Carbohydrates in the diet

The proportion of carbohydrates in the diet of children largely depends on age. In children of the first year of life, the carbohydrate content that provides the need for energy is 40%. After one year, it increases to 60%. In the first months of life, the need for carbohydrates is covered by milk sugar - lactose, which is part of breast milk. With artificial feeding with milk formulas, the child also receives sucrose or maltose. After the introduction of complementary foods, polysaccharides (starch, partly glycogen) begin to enter the body, which mainly cover the body's need for carbohydrates. This type of nutrition for children promotes both the formation of amylase by the pancreas and its secretion with saliva. In the first days and weeks of life, amylase is practically absent, and salivation is insignificant, and only from 3-4 months does the secretion of amylase begin and salivation increases sharply.

It is known that starch hydrolysis occurs under the influence of salivary amylase and pancreatic juice; starch is broken down into maltose and isomaltose.

Along with food disaccharides - lactose and sucrose - maltose and isomaltose on the surface of the intestinal villi of the intestinal mucosa under the influence of disaccharidases are broken down into monosaccharides: glucose, fructose and galactose, which are resorbed through the cell membrane. The process of glucose and galactose resorption is associated with active transport, which consists of phosphorylation of monosaccharides and their conversion into glucose phosphate, and then into glucose-6-phosphate (respectively, galactose phosphates). Such activation occurs under the influence of glucose- or galactose kinases with the expenditure of one macroergic bond of ATP. In contrast to glucose and galactose, fructose is resorbed almost passively, by simple diffusion.

Disaccharidases in the fetal intestine are formed depending on the gestational age.

Timing of the development of gastrointestinal tract functions, timing of detection and severity as a percentage of the same function in adults

Carbohydrate absorption	First detection of the enzyme, week	Severity, % of adult
A-Amylase pancreatic	22	5
Α-Amylase of salivary glands	16	10
Lactase	10	More than 100
Sucrase and isomaltase	10	100
Glucoamylase	10	50
Absorption of monosaccharides	11	92

It is evident that the activity of maltase and sucrase increases earlier (6-8 months of gestation), and later (8-10 months) - lactase. The activity of various disaccharidases in the cells of the intestinal mucosa was studied. It was found that the total activity of all maltases by the time of birth corresponds to an average of 246 μmol of split disaccharide per 1 g of protein per minute, the total activity of sucrase - 75, the total activity of isomaltase - 45 and the total activity of lactase - 30. These data are of great interest to pediatricians, since it becomes clear why a breastfed baby digests dextrin-maltose mixtures well, while lactose easily causes diarrhea. The relatively low activity of lactase in the mucous membrane of the small intestine explains the fact that lactase deficiency is observed more often than deficiency of other disaccharidases.

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Impaired carbohydrate absorption

There are both transient and congenital lactose malabsorption. The first form is caused by a delay in the maturation of intestinal lactase and therefore disappears with age. The congenital form can be observed for a long time, but, as a rule, is most pronounced from birth during breastfeeding. This is explained by the fact that the lactose content in human milk is almost 2 times higher than in cow's milk. Clinically, the child develops diarrhea, which is characterized by, along with loose stools (more than 5 times a day), foamy stools of an acidic reaction (pH less than 6). Symptoms of dehydration may also be observed, manifesting themselves as a serious condition.

At an older age, the so-called lactase repression occurs, when its activity is significantly reduced. This explains the fact that a significant number of people do not tolerate natural milk, while fermented milk products (kefir, acidophilus, yogurt) are well absorbed. Lactase deficiency affects about 75% of people of African and Indian descent, up to 90% of people of Asian descent and 20% of Europeans. Congenital malabsorption of sucrose and isomaltose is less common. It usually manifests itself in children with artificial feeding with milk mixtures enriched with sucrose, and with the introduction of juices, fruits or vegetables containing this disaccharide into the diet. Clinical manifestations of sucrose deficiency are similar to those of lactose malabsorption. Disaccharidase deficiency can also be purely acquired, be a consequence or complication of a wide range of diseases suffered by the child. The main causes of disaccharidase deficiency are listed below.

Consequence of exposure to damaging factors:

• after enteritis of viral or bacterial etiology;
• the special significance of rotavirus infection;
• malnutrition;
• giardiasis;
• after necrotic enterocolitis;
• immunological deficiency;
• celiac disease;
• cytostatic therapy;
• cow's milk protein intolerance;
• hypoxic conditions of the perinatal period;
• Jaundice and its phototherapy.

Immaturity of brush border:

• prematurity;
• immaturity at birth.

Consequences of surgical interventions:

• gastrostomy;
• ileostomy;
• colostomy;
• small bowel resection;
• small intestinal anastomoses.

Similar clinical manifestations have been described in cases of impaired activation of monosaccharides - glucose and galactose. They should be distinguished from cases when the diet contains too much of these monosaccharides, which, having high osmotic activity, cause water to enter the intestine. Since monosaccharides are absorbed from the small intestine into the V. portae pool, they first enter the liver cells. Depending on the conditions, which are determined mainly by the glucose content in the blood, they are converted into glycogen or remain as monosaccharides and are carried with the blood flow.

In the blood of adults, the glycogen content is slightly lower (0.075-0.117 g/l) than in children (0.117-0.206 g/l).

The synthesis of the body's reserve carbohydrate - glycogen - is carried out by a group of different enzymes, resulting in the formation of highly branched molecules consisting of glucose residues that are linked by 1,4- or 1,6-bonds (the side chains of glycogen are formed by 1,6-bonds). If necessary, glycogen can again be broken down into glucose.

Glycogen synthesis begins in the 9th week of intrauterine development in the liver. However, its rapid accumulation occurs only before birth (20 mg/g of liver per day). Therefore, the concentration of glycogen in the liver tissue of the fetus at birth is somewhat higher than in an adult. Approximately 90% of the accumulated glycogen is used in the first 2-3 hours after birth, and the remaining glycogen is consumed within 48 hours.

This, in fact, provides the energy needs of newborns in the first days of life, when the child receives little milk. From the 2nd week of life, glycogen accumulation begins again, and by the 3rd week of life, its concentration in the liver tissue reaches the adult level. However, the liver mass in children is significantly less than in adults (in children aged 1 year, the liver mass is equal to 10% of the liver mass of an adult), so glycogen reserves in children are used up faster, and they must replenish it to prevent hypoglycemia.

The ratio of the intensity of glycogenesis and glycogenolysis processes largely determines the blood sugar content - glycemia. This value is quite constant. Glycemia is regulated by a complex system. The central link in this regulation is the so-called sugar center, which should be considered as a functional association of nerve centers located in various parts of the central nervous system - the cerebral cortex, subcortex (lenticular nucleus, striatum), hypothalamic region, medulla oblongata. Along with this, many endocrine glands (pancreas, adrenal glands, thyroid) participate in the regulation of carbohydrate metabolism.

Disorders of carbohydrate metabolism: storage diseases

However, congenital disorders of enzyme systems may be observed, in which the synthesis or breakdown of glycogen in the liver or muscles may be disrupted. These disorders include glycogen deficiency disease. It is based on a deficiency of the enzyme glycogen synthetase. The rarity of this disease is probably explained by the difficulty of diagnosis and a rapid unfavorable outcome. Newborns experience hypoglycemia very early (even between feedings) with convulsions and ketosis. More often, cases of glycogen disease are described, when glycogen of normal structure accumulates in the body or glycogen of an irregular structure resembling cellulose (amylopectin) is formed. This group, as a rule, is genetically determined. Depending on the deficiency of certain enzymes involved in glycogen metabolism, various forms or types of glycogenoses are distinguished.

Type I, which includes hepatorenal glycogenosis, or Gierke's disease, is based on glucose-6-phosphatase deficiency. This is the most severe form of glycogenosis without structural glycogen disorders. The disease is recessive; clinically manifests itself immediately after birth or in infancy. Hepatomegaly is characteristic, which is accompanied by hypoglycemic seizures and coma, ketosis. The spleen never increases in size. Later, growth retardation and body disproportion are observed (the abdomen is enlarged, the body is elongated, the legs are short, the head is large). In between feedings, pallor, sweating, and loss of consciousness are observed as a result of hypoglycemia.

Type II glycogenosis - Pompe disease, which is based on acid maltase deficiency. It manifests clinically soon after birth, and such children die quickly. Hepato- and cardiomegaly, muscle hypotonia are observed (the child cannot hold his head or suck). Heart failure develops.

Type III glycogenosis - Cori disease, caused by a congenital defect of amylo-1,6-glucosidase. Transmission is recessive-autosomal. Clinical manifestations are similar to type I - Gierke disease, but less severe. Unlike Gierke disease, this is a limited glycogenosis, not accompanied by ketosis and severe hypoglycemia. Glycogen is deposited either in the liver (hepatomegaly), or in the liver and simultaneously in the muscles.

Type IV - Andersen's disease - is caused by a deficiency of 1,4-1,6-transglucosidase, resulting in the formation of glycogen of an irregular structure resembling cellulose (amylopectin). It is like a foreign body. Jaundice and hepatomegaly are observed. Liver cirrhosis with portal hypertension develops. As a result, varicose veins of the stomach and esophagus develop, the rupture of which causes profuse gastric bleeding.

Type V - muscle glycogenosis, McArdle's disease - develops due to a deficiency of muscle phosphorylase. The disease may manifest itself in the 3rd month of life, when it is noted that children are not able to suckle for a long time, and quickly get tired. Due to the gradual accumulation of glycogen in the striated muscles, its false hypertrophy is observed.

Type VI glycogenosis - Hertz disease - is caused by a deficiency of hepatic phosphorylase. Clinically, hepatomegaly is detected, hypoglycemia occurs less often. Growth retardation is noted. The course is more favorable than in other forms. This is the most common form of glycogenosis.

Other forms of storage diseases are also observed, when mono- or polyenzyme disorders are detected.

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Blood sugar as an indicator of carbohydrate metabolism

One of the indicators of carbohydrate metabolism is the blood sugar level. At the moment of birth, the child's glycemia level corresponds to that of its mother, which is explained by free transplacental diffusion. However, from the first hours of life, a drop in sugar content is observed, which is explained by two reasons. One of them, the more significant one, is the lack of counter-insular hormones. This is proven by the fact that adrenaline and glucagon are able to increase the blood sugar level during this period. Another reason for hypoglycemia in newborns is that glycogen reserves in the body are very limited, and a newborn who is put to the breast a few hours after birth uses them up. By the 5th-6th day of life, the sugar content increases, but in children it remains relatively lower than in adults. The increase in sugar concentration in children after the first year of life is wave-like (the first wave - by the age of 6, the second - by the age of 12), which coincides with the increase in their growth and a higher concentration of somatotropic hormone. The physiological limit of glucose oxidation in the body is 4 mg/(kg • min). Therefore, the daily dose of glucose should be from 2 to 4 g/kg of body weight.

It should be emphasized that the utilization of glucose during its intravenous administration occurs faster in children than in adults (it is known that intravenously administered glucose is utilized by the body, as a rule, within 20 minutes). Therefore, the tolerance of children to the carbohydrate load is higher, which must be taken into account when studying glycemic curves. For example, to study the glycemic curve, an average load of 1.75 g / kg is used.

At the same time, children have a more severe course of diabetes mellitus, for the treatment of which, as a rule, it is necessary to use insulin. Diabetes mellitus in children is most often detected during periods of particularly intensive growth (the first and second physiological extensions), when a violation of the correlation of endocrine glands is more often observed (the activity of the somatotropic hormone of the pituitary gland increases). Clinically, diabetes in children is manifested by thirst (polydipsia), polyuria, weight loss and often an increase in appetite (polyphagia). An increase in blood sugar (hyperglycemia) and the appearance of sugar in the urine (glucosuria) are detected. Ketoacidosis is common.

The disease is based on insulin deficiency, which makes it difficult for glucose to penetrate cell membranes. This causes an increase in its content in the extracellular fluid and blood, and also increases the breakdown of glycogen.

In the body, glucose can be broken down in several ways. The most important of these are the glycolytic chain and the pentose cycle. Breakdown along the glycolytic chain can occur both aerobic and anaerobic conditions. Under aerobic conditions, it leads to the formation of pyruvic acid, and under anaerobic conditions, lactic acid.

In the liver and myocardium, the processes proceed aerobically, in erythrocytes - anaerobically, in skeletal muscles during intense work - predominantly anaerobically, during rest - predominantly aerobic. The aerobic path is more economical for the organism, since it results in the formation of more ATP, which carries a large reserve of energy. Anaerobic glycolysis is less economical. In general, through glycolysis, cells can quickly, although uneconomically, be supplied with energy regardless of the "delivery" of oxygen. Aerobic breakdown in the combination of the glycolytic chain - Krebs cycle is the main source of energy for the organism.

At the same time, by reverse flow of the glycolytic chain, the body can synthesize carbohydrates from intermediate products of carbohydrate metabolism, such as pyruvic and lactic acids. The conversion of amino acids into pyruvic acid, α-ketoglutarate and oxalacetate can lead to the formation of carbohydrates. The processes of the glycolytic chain are localized in the cytoplasm of cells.

A study of the ratio of glycolytic chain metabolites and the Krebs cycle in the blood of children shows quite significant differences compared to adults. The blood serum of a newborn and a child of the first year of life contains a fairly significant amount of lactic acid, which indicates the prevalence of anaerobic glycolysis. The child's body tries to compensate for the excess accumulation of lactic acid by increasing the activity of the enzyme lactate dehydrogenase, which converts lactic acid into pyruvic acid with its subsequent inclusion in the Krebs cycle.

There are also some differences in the content of lactate dehydrogenase isoenzymes. In young children, the activity of the 4th and 5th fractions is higher and the content of the 1st fraction is lower.

Another, no less important, way of splitting glucose is the pentose cycle, which begins with the glycolytic chain at the level of glucose-6-phosphate. As a result of one cycle, one of the 6 glucose molecules is completely split into carbon dioxide and water. This is a shorter and faster decay path, which provides the release of a large amount of energy. As a result of the pentose cycle, pentoses are also formed, which are used by the body for the biosynthesis of nucleic acids. This probably explains why the pentose cycle is of great importance in children. Its key enzyme is glucose-6-phosphate dehydrogenase, which provides the connection between glycolysis and the pentose cycle. The activity of this enzyme in the blood of children aged 1 month - 3 years is 67-83, 4-6 years - 50-60, 7-14 years - 50-63 mmol / g hemoglobin.

Disruption of the pentose cycle of glucose breakdown due to deficiency of glucose-6-phosphate dehydrogenase underlies non-spherocytic hemolytic anemia (one of the types of erythrocytopathy), which is manifested by anemia, jaundice, splenomegaly. As a rule, hemolytic crises are provoked by taking medications (quinine, quinidine, sulfonamides, some antibiotics, etc.), which increase the blockade of this enzyme.

A similar clinical picture of hemolytic anemia is observed due to the deficiency of pyruvate kinase, which catalyzes the conversion of phosphoenolpyruvate into pyruvate. They are distinguished by a laboratory method, determining the activity of these enzymes in erythrocytes.

Disruption of glycolysis in platelets underlies the pathogenesis of many thromboasthenias, clinically manifested by increased bleeding with a normal number of platelets, but impaired function (aggregation) and intact blood coagulation factors. It is known that the main energy metabolism of a person is based on the use of glucose. The remaining hexoses (galactose, fructose), as a rule, are transformed into glucose and undergo complete breakdown. The conversion of these hexoses into glucose is carried out by enzyme systems. Deficiency of enzymes that transform this conversion underlies gstactosemia and fructosemia. These are genetically determined enzymopathies. In gstactosemia, there is a deficiency of galactose-1-phosphate uridyl transferase. As a result, galactose-1-phosphate accumulates in the body. In addition, a large amount of phosphates is removed from the circulation, which causes a lack of ATP, causing damage to energy processes in cells.

The first symptoms of galactosemia appear soon after the start of feeding children with milk, especially breast milk, which contains a large amount of lactose, which includes equal amounts of glucose and galactose. Vomiting appears, body weight increases poorly (hypotrophy develops). Then hepatosplenomegaly with jaundice and cataracts appear. Ascites and varicose veins of the esophagus and stomach may develop. Urine examination reveals galactosuria.

In case of galactosemia, lactose must be excluded from the diet. Specially prepared milk formulas are used, in which the lactose content is sharply reduced. This ensures the correct development of children.

Fructosemia develops when fructose is not converted into glucose due to a deficiency of fructose-1-phosphate aldolase. Its clinical manifestations are similar to those of galactosemia, but are expressed to a milder degree. Its most characteristic symptoms are vomiting, a sharp decrease in appetite (up to anorexia), when children are given fruit juices, sweetened cereals and purees (sucrose contains fructose and glucose). Therefore, clinical manifestations are especially aggravated when children are transferred to mixed and artificial feeding. At an older age, patients do not tolerate sweets and honey, which contains pure fructose. Fructosuria is detected when examining urine. It is necessary to exclude sucrose and products containing fructose from the diet.