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Файл:Carbohydrates. Bioenergetics. Study manual
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teoglycans and glycosaminoglycans can perform in the human body the following
functions:
proteoglycans and glycosaminoglycans specifically interact with collagen,
elastin, a fibronectin, laminin and other proteins of the extracellular matrix;
they are structural components of the extracellular matrix;
all proteoglycans and glycosaminoglycans, as polyanions, you can join, be-
sides water, large amounts of cations (Na+,K+, Ca2+) and thus participate in the formation of turgor of various tissues;
hyaluronic acid and proteoglycans perform spring function in articular carti-
lage;
heparansulfate proteoglycans contribute to the creation of the filtration barrier
in the kidney;
keratansulfate and dermatosurgery ensure the transparency of the cornea;
heparin – an anticoagulant;
heparansulfate components of the plasma membrane of cells where they may
function as receptors and participate in cell adhesion and intercellular interactions.
They also are components of synaptic and other vials;
proteoglycans and glycosaminoglycans play a role of molecular sieves in the
intercellular matrix, they prevent the spread of pathogenic microorganisms.
Currently known structure of six major classes of glycosaminoglycans – hyaluronic acid, chondroitin sulfate and keratansulfate, dermatan sulfate, heparin,
heparansulfate.
Hyaluronic acid is found in the tissues of many organs. In cartilage it is associated with protein and is involved in the formation proteoglycan units in some organs
(vitreous body of the eye, umbilical cord, joint fluid) found in free form. It is assumed that in joint fluid, hyaluronic acid acts as lubricant, reducing friction between
the articular surfaces. The repeating structural unit in hyaluronic acid is a disaccharide and has the following structure:
Hyaluronic acid can contain several thousand disaccharide units, the molecular
weight it reaches 105- 107Da.
Chondroitinsulfates the most common glycosaminoglycans in the human body;
they are found in cartilage, skin, tendons, ligaments, arteries, cornea of the
eye. Chondroitin sulfate is an integral and important component of the cartilage matrix. In humans there are two types of chondroitin sulfate: chondroitin-4-sulfate and
chondroitin-6-sulfate, which differ only in the position of sulphate group in the
molecule N-acetylgalactosamin.
One polysaccharide chain of chondroitin sulfate contains about 40 repeating disaccharide units and has a molecular weight of 104–106Da.
Keratansulfate glycosaminoglycans, which are different from each other in the
total carbohydrate content and distribution in different tissues. Keratan sulfateI is located in the cornea of the eye and contains besides the repeating disaccharide unit Lfucose, D-mannose and sialic acid. Keratan sulfateII was discovered in the cartilage,
bones, intervertebral discs. In its composition in addition to disaccharide units composed of N-acetylgalactosamin, L-fucose, D-mannose and sialic acid. Unlike other
glycosaminoglycans, the keratansulfate hexuronic acid contain galactose residue.
The molecular weight of one chain of a keratan sulfate, ranging from 4 × 103to
20 × 103Da.
Dermatan sulfate it is widely distributed in animal tissues, especially it is characteristic of the skin, blood vessels, heart valves. In the small proteoglycans (decorin
and biglycan) dermatan sulfate is contained in the intercellular substance of cartilage, intervertebral discs, menisci. The repeating disaccharide unit of dermatan sulfate has the following structure
The molecular weight of one chain of dermatan sulfate ranges from 15 × 103up
to 40 × 103Da.
Heparin – an important component of the anticoagulation system of blood (it is
used as a pharmacological drug, an anticoagulant in the treatment of thrombosis). It
is synthesized by mast cells and is located in granules within these cells. Heparin is a
mucopolysaccharide composed of glucosamine, glucuronic acid and essential associated sulfuric acid. The greatest amount of heparin detected in the lungs, liver, and
skin. Disaccharide unit of heparin is similar to the disaccharide unit of heparansulfate. The difference between these glycosaminoglycans is that in the heparin more
N-sulfate groups, and heparansulfate more N-acetyl groups.
The biological significance of heparin is determined by its ability to delay the
clotting of blood. Heparin can form complexes with a number of proteins, including
some enzymes.
Heparin is now widely used as a natural stabilizer of blood in her transfusion, as
well as a means to prevent thrombosis.
The molecular weight of heparin ranges from 6 × 103up to 25 × 103Da.
Heparansulfate is found in many organs and tissues. It is part of the proteoglycans
of the basal membranes. Heparansulfate is a permanent component of the cell surface.
The structure of the disaccharide units of heparansulfate the same as that of heparin. The
molecular weight of the chain heparansulfate ranges from 5 × 103to 12 × 103Da.
Glycoproteins – complex proteins, prosthetic group to which different carbohydrates and their derivatives. Examples of glycoproteins are: transport proteins (transferrin, transcortin, haptoglobin, etc.), blood coagulation factors (prothrombin, fibrinogen), immunoglobulins, enzymes (ribonuclease B, cholinesterase), hormones
(thyrotropin, gonadotropin, etc.). Cellular glycoproteins on the surface membranes
provide the specificity of intercellular contacts, affect the differentiation of tissues. Collagen is the most abundant glycosylated protein in the human body; it accounts for approximately 1/3 of the total number of proteins. The structure of collagen gives tissues mechanical strength and derestimate. Tendons, that the muscles attached to the bones, consists mainly of collagen fibers that are intertwined and crisscrossed to form a non-stretchable and very durable structure. Similar structures are
the basis of skin, connective tissue, organic matrix of bones, teeth. Non-protein part
of the collagen – component carbohydrate – monosaccharide (galactose) and disaccharide (galactose-glucose) residues. The carbohydrate components linked to the
protein via the hydroxyl groups of some residues hydroxylysine (glycosidic bond).
1.5. The biological role and function of carbohydrates in the body
Carbohydrates with proteins, lipids and nucleic acids are part of living organisms and determine the specificity of their structure and functioning. Carbohydrates
account for about 75 % of the weight of the diet and more than 50 % of the daily
calories needed.Carbohydrates are an energy source and perform a structural role.
From carbohydrates in the metabolism processes of the substance are formed, which
serve as the initial substrates for the synthesis of lipids, amino acids, nucleotides.
The daily requirement of 500 grams.
Carbohydrates perform in the body the following features.
1. Energy. Carbohydrates are the main source of energy in the body. They account for more than 60% of the energy required by the human. The basic fuel for
brain cells, red blood cells is glucose. In the decay of 1 gram of carbohydrates 4.1
kcal formed or 17.6 kJ of energy.
2. Backup. Carbohydrates are stored in plants in form of starch and in the body
in the form of glycogen. Glycogen deposited in the cytoplasm of liver cells, muscles
and consumed as needed.
3. Plastic (structural). Carbohydrates make up the different organs and tissues:
glycoproteins – collagen; proteins-receptors; glycocalyx. proteins determine the
group membership of blood; blood coagulation factors; enzymes, hormones; glycosaminoglycans, etc.;
Carbohydrates (ribose, a deoxyribose) are part of nucleic acids, free mononu-
cleotides (ATP, GTP, cAMP, etc.), coenzymes (NAD+, NADP, FAD);
4. Regulatory. Fiber due to its rough fibrous structure increases intestinal peristalsis, promotes the formation of feces.
5. Specific function. Carbohydrates determine specificity of the blood to form
clotting factors; enzymes, hormones; glycosaminoglycans, etc.;
6. The protective function. Part of immunoglobulins, interferon, and
mucins,fibrinogen, glycosaminoglycans etc.
7. Detoxification. Carbohydrates be part of PAPS (phosphoadenylylsulfate) and
UDPA (uridinediphosphate acid).
1.6. Digestion and absorption of carbohydrates
Carbohydrate metabolism plays an important role in the functioning of the
body. Catabolism of carbohydrates, on the one hand, is accompanied by a release of
energy that can be accumulated in macroergic ATP and links be used further for the
synthesis of essential molecular components of cells and perform various types of
work, on the other hand, both metabolites are initial substances for the formation of
biologically important compounds such as amino acids, lipids, nucleotides. The
main dietary carbohydrates are starch and disaccharides. For adults, the daily requirement for carbohydrates is 400–600 g; for children 12 g/kg.
Once in the gastrointestinal tract, carbohydrates under the action of enzymes
break down into monosaccharides and are absorbed by epithelial cells of the jejunum and ileum of the intestines with the help of special transport mechanisms
through the membranes of these cells (by facilitated diffusion and active transport).
In the mouth the food is crushed when chewed, wetted with saliva, the pH of
which is equal to 6.8. Under the influence of α-amylase saliva (endoamylase) fission
occurs in the starch-α-1,4-glycosidic linkages. She cleaves α-1,6-glycosidic bonds in
starch, so starch is digested only partially with the formation of large fragments,
dextrins and small amount of maltose. α-amylase does not hydrolyze the glycosidic
bond in disaccharides.
In the stomach the action of salivary amylase stopped because the pH of gastric
juice is 1.5 to 2.5. However, inside the food bolus amylase activity may for a while
be preserved, until the pH will not change to the acid side.
The enzymes of the intestine presented α-glucosidase and β-glucosidase carrying out digestion of carbohydrates. The main intestinal enzymes include: maltase
(breaks down the 1,4 – alpha glycosidic bond in the disaccharide maltose), isomaltase (cleaves 1,6 – glycosidic bonds in starch), sucrase (splits 1, 2 – α-β glycosidic
bond in the disaccharide sucrose), lactase (breaks down the 1,4 – β-glycosidic bond
in the disaccharide lactose), heterogenesis – cleaves glycosidic bonds of mixed oligosaccharides.
In the duodenum the pH is equal to 7.5 to 8.0. From the pancreas into the intestine receives pancreatic α-amylase. This enzyme is also because endoglycosidase
cleaves α-1,4-glycosidic bonds in starch and dextrins. Products of digestion: oligosaccharides containing 3 to 8 glucose residues, maltose, isomaltose – a disaccharide
consisting of 2 molecules of α-D-glucose connected by α-1,6-glycoside
bond. Further splitting occurs in the lower parts of the small intestine under the action of enzymes – maltase, isomaltase. The food disaccharides sucrose and lactose
also broken down in the small intestine by lactase and sucrase (cavity digestion).
The process of digestion ends on the surface of epithelial intestinal cells (membrane, digestion). Epithelial cells covered with microvilli, over which there is a fibrous network of the glycocalyx (glycoprotein). There are enzymes hydrolyzing
maltose, sucrose, lactose, which are not splintered in the cavity of the intestine.
The rate of absorption of the various monosaccharides, glucose and galactose
are absorbed faster than other monosaccharides. Transport of monosaccharides in
the cell the intestinal mucosa can be done in several ways: through facilitated diffusion and active transport. At high concentrations of glucose in the intestinal lumen,
it is transported into the cell by facilitated diffusion. At low concentrations, glucose
is absorbed by active transport.
The mechanism of active transport. Glucose and Na+cations connect with dif-
ferent parts of the protein-carrier. In this Na+taken up into the cell against a concentration gradient and at the same time glucose is transported against the concentration
gradient. The greater the gradient of the Na+the more the supply of glucose in the
enterocytes. If the concentration of Na+decreases glucose transport is reduced. The
free energy required for active transport is generated by hydrolysis of ATP linked to
a sodium pump, which removes from the cells of the Na+in exchange for K+. Glucose connects to another protein carrier by facilitated diffusion is absorbed into the
bloodstream.
The role of fiber in digestion
Fiber (cellulose) is a polysaccharide, which is decomposed in the human body,
since this enzyme system in humans is not. However, the intake of fiber in the food
composition is necessary, because it performs many functions:
1) irritating the nerve endings of the mucous membrane of the intestine, in-
creases intestinal peristalsis;
2) increases secretion of intestinal juice;
3) contributes to the formation of stool;
4) adsorb cholesterol;
5) adsorbs heavy metals, radionuclides;
6) in the intestine subjected to alcoholic fermentation, inhibits the proliferation
of putrefactive bacteria.
1.7. The breakdown of glucose
The breakdown of glucose is possible in two ways. One of them is the collapse
of the six-carbon glucose molecule into two three-carbon molecules. This path is
called a dichotomous breakdown of glucose. If the second path loss occurs the glucose molecule one atom of carbon, which leads to the formation of pentoses; this
path is called apotomic breakdown.
The dichotomous breakdown of glucose can occur under anaerobic (without
presence of oxygen) and aerobic (in the presence of oxygen) conditions. From the
breakdown of glucose under anaerobic conditions as a result of the process of lactic
fermentation converted into lactic acid. Otherwise, the process is called the glycoly-
sis (from the Greek. glicos – sweet, lysis – dissolution).
Glycolysis
Glycolysis is an anaerobic process, i.e. the oxidation reactions are not accompanied by transfer of hydrogen or electrons in the respiratory chain and then to oxygen. Intermediate products of glycolysis are hexose phosphate and triose phosphate. Such compounds as glucose-6-phosphate and glyceraldehyde-3-phosphate,
are intermediate products that are common to glycolysis and pentoses cycle. Lactate
is formed from pyruvate by the action of lactate dehydrogenase is the final product
of glycolysis in the cells of animals and humans under anaerobic conditions. Only a
small part of the energy contained in a molecule of glucose is released during glycolysis. Synthesized only 2 moles of ATP for each mole of glucose. The reactions of
glycolysis occur in the cytoplasm and not associated with cellular structures. The intensity of the process of glycolysis decreases in the presence of oxygen (the Pas-
teur's effect).
The individual reactions of glycolysis catalyze the 11 enzymes that form a
chain in which the product of the reaction, accelerated by a preceding enzyme is the
substrate for the next. Glycolysis can be divided into two stages. In the first stage,
the energy, the second stage, on the contrary, is characterized by the accumulation of
energy in the form of ATP molecules.
The first reaction of glycolysis is phosphorylation of glucose with formation of
glucose-6-phosphate. Glucose-6-phosphate further isomerized in fructose-6phosphate, which is phosphorylated to fructose-1,6-diphosphate. The next reaction is
lyase splitting of fructose-1,6-diphosphate to two trios-3-phosphoglyceraldehyde
and phosphodioxyacetone. The first phase of glycolysis ends with formation of these
trioses:
Phosphorylation of fructose-6-phosphate to fructose-1,6 diphosphate, catalyzed
by phosphofructokinase is a key glycolytic reaction paths occurring in the tissues. Phosphofructokinase – allosteric enzyme whose activity decreases in the presence of ATP and citrate, and grows in the presence of AMP and ADP.
In the second stage of glycolysis enter 2 molecules of 3-phosphoglyceraldehyde,
one of which is formed directly in the cleavage of fructose-1,6-diphosphate, and the
other by isomerization of phosphodioxyacetone.
The second phase of glycolysis is opened by oxidation of 3-phosphoglyceraldehyde
of aldehyde catalyzed by a specific dehydrogenase that contains in the active site of the
free sulfhydryl (HS-) group and the coenzyme NAD. The result is a 1,3-diphosphoglyceric acid. Next is the transfer of a phosphate group to the ADP molecule; thus
there is storage of energy in macroergic bonds of ATP molecule. Since formed in
glycolysis 2 molecules of 1,3-diphosphoglyceric acid, and there are 2 molecules of
ATP. Isomerization of the previous metabolite 2-phosphoglyceraldehyde acid required for the reaction of dehydration is accelerated corresponding lyase, with the
formation of macroergic compounds – phosphoenolpyruvate acid, which then gives
the phosphate group to the molecule ADP. The result is 2 molecules of ATP and pyruvic acid (pyruvate). The final reaction of this metabolic pathway is lactic acid,
which is formed by the recovery of pyruvic acid.
A significant part of lactic acid formed in muscle, gets into the bloodstream,
which can cause a change in blood pH, i.e. acidification – acidosis. Bicarbonate
buffer system in the blood in this case regulates the pH. Thus, in athletes, buffering
capacity of blood increased compared with untrained people, so they can tolerate
higher levels of lactic acid, which in large number are formed in the course of training, physical loads. Further, lactic acid is transported to the liver and kidneys, where
it is almost fully processed into glucose and glycogen. A small part of lactic acid is
again converted into pyruvic acid, which under aerobic conditions is oxidized to end
products of metabolism.
In total, the process of glycolysis is expressed by the equation
С6Н12О6 + 2NАD+ + 2АDP + 2Н3РО4→
2СН3СОСООН + 2NАDН + 2Н+ + 2АТP
1.8. The pentose phosphate pathway of glucose oxidation
Pentose phosphate pathway – an alternative route of glucose oxidation. Its functions are:
– supplies cells of the coenzyme NADPH, which is used as a hydrogen donor in
the reactions of recovery;
– provides the cells with pentose phosphate for the synthesis of nucleotides and
nucleic acids.
The pentose phosphate pathway leads to the synthesis of ATP.
The enzymes involved in the reactions of pentose phosphate pathway, localized
in the cytosol of the cell.
In pentose phosphate pathway the transformation of glucose secrete oxidative
and non-oxidative path of the pentose education.
The oxidative pathway involves two reactions of dehydrogenation. Coenzyme
dehydrogenases is NADP+reduction of NADPH. Pentose are formed by the oxidative decarboxylation.
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