Добавил:
ivanov666
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Carbohydrates. Bioenergetics. Study manual
.pdf
An example of a hereditary intolerance to monosaccharaides is fructose intolerance, which is caused by a genetic defect protosatellite and in some cases, decreased
activity of fructose-1,6-diphosphate-aldolase. The disease is characterized by lesions
of the liver and kidneys. For clinical picture characterized cramps, frequent vomiting,
and sometimes coma. The symptoms of the disease appear in the first months of life
when transferring children to mixed or artificial feeding. Load of fructose cause sudden hypoglycemia.
Diseases caused by defects of enzymes involved in the metabolism of oligosaccharides, mainly because violation of digestion and absorption of carbohydrates,
which occurs mainly in the small intestine.
Maltose and low molecular weight dextrins formed from starch and glycogen of
food under the action -amylase of saliva and pancreatic juice, lactose in milk and
sucrose are broken down by disaccharidases (maltase, lactase and sucrose) to the
corresponding monosaccharaides mainly in the microvilli of the mucosa of the small
intestine, and then, if the process of transport of monosaccharides is not broken, is
their suction. The absence or reduced activity of disaccharidases to the mucosa of
the small intestine is the main cause of intolerance of the corresponding disaccharide, which often leads to liver and kidneys, cause diarrhea, flatulence (see Malab-
sorption syndrome). Particularly severe symptoms are characterized by a hereditary
intolerance to lactose, found usually with the birth of the child.
For the diagnosis of intolerance to the sugars used are usually stress test with
the introduction of on an empty stomach carbohydrate intolerance which I suspect. More accurate diagnosis can be made by biopsy of the intestinal mucosa and
determining in the obtained material the activity of disaccharidases. Treatment consists in the elimination of food products containing the corresponding disaccharide. A greater effect is observed, however, the appointment of enzyme preparations,
allowing such patients to eat regular food. For example, in case of insufficiency of
lactase containing enzyme preparation, it is desirable to add the milk before eating
it in food. Proper diagnosis of diseases caused by deficiency of disaccharidases, is
extremely important. The most common diagnostic error in these cases are establishing
a false diagnosis of dysentery, other intestinal infections and antibiotic treatment,
resulting in rapid deterioration of sick children and severe consequences.
The disease caused by metabolic disorders of glycogen, constitute a group of
hereditary enzymopathies, United under the name of glycogen storage. Glyco-
genoses are characterized by excessive accumulation of glycogen in cells, which
may also be accompanied by a change in the molecular structure of this polysaccharide. Glycogenoses include the so-called diseases of accumulation. Glycogenosis
(glycogenic disease) are inherited in an autosomal recessive or sex-linked type.
The almost complete absence in cells of glycogen is observed at glycogenase, which
is caused by the absence or reduced activity of the glycogen of the liver. The disease
is caused by a metabolic different glycoconjugates, in most cases are the result of
congenital defects of the breakdown of glycolipids, glycoproteins or glycosaminoglycans (mucopolysaccharides) in various organs. They also are diseases of ac-
cumulation. Depending on which connection abnormally accumulates in the body,
there are glycolipids, glycoproteinods, mucopolysaccharides. A lysosomal glycosidase, a defect which is the basis of hereditary disorders of carbohydrate metabolism,
exist in a variety of shapes, so-called multiple forms, or isoenzymes. The disease can
be caused by the defect of any one isoenzyme. So, for example, the disease Tay-
Sachs – the effect of a defect forms N-acetylglucosaminidase (hexosaminidase A),
while the defect forms A and B of this enzyme leads to Sandhoff’sdisease. The majority of storage diseases, runs extremely hard, many of them are still incurable. The
clinical picture in various diseases accumulation may be similar, and, conversely,
the same disease can manifest differently in different patients. It is therefore necessary in each case to establish the enzyme defect is detected predominantly in leukocytes and skin fibroblasts of the patients. As substrates used glycoconjugate or various synthetic glycosides. At various the mucopolysaccharidases, and in some other
diseases of accumulation (for example, when mannosidose) excreted in the urine in
significant quantities differing in the structure of oligosaccharides. The release of
these compounds from urine and their identification is carried out to diagnose diseases of accumulation.
In some diseases of serious disruptions of carbohydrate metabolismoccur
again. An example of such a disease is diabetes mellitus caused or defeat -cells of
the islets of the pancreas, or defects in the structure of insulin or its receptors on cell
membranes insulin-sensitive tissues. Alimentary hyperglycemia and hyperinsulinemia lead to the development of obesity, which increases lipolysis and the use of
unesterified fatty acids (UEFA) as energy substrate. This impairs glucose utilization
in muscle tissue and stimulates gluconeogenesis. In turn, the excess blood UEFA
and insulin leads to increased liver synthesis of triglycerides and cholesterol and,
consequently, increase concentration in the blood lipoproteinosis low and low density. One of the reasons contributing to the development of such severe complications of diabetes like cataracts, nephropathy, angiopathy and tissue hypoxia, which
is non-enzymatic glycosylation of proteins.
The mucopolysaccharidoses – heavy hereditary disease, manifested significant
impairments in the mental development of children, lesions of the vessels, clouding
of the cornea, deformities of the skeleton, reduction of life expectancy. The basis of
mucopolysaccharidoses are hereditary defects in any of the hydrolases involved in
the catabolism of glycosaminoglycans. These diseases are characterized by excessive accumulation of glycosaminoglycans in tissues, leading to deformation of the
skeleton and increase of bodies containing large amounts of extracellular matrix.
Usually affects tissues in which normal synthesized the greatest quantities of glycosaminoglycans. In the lysosomes thus accumulate not completely destroyed glycosaminoglycans and urine is their oligosacharide fragments. There are several types of mucopolysaccharidoses caused by defects in different enzymes in the hydrolysis of glycosaminoglycans. The main types of mucopolysaccharidoses are given in the table.
For the diagnosis of a specific disease usually determine the activity of ly-
Name
disease
Products
accumulation
Defective
enzyme
The symptoms
of the disease
Disease
Hurler
Dermatan Sulfate
Heparansulfate
α-L-iduronidase
observed thickening of the skull
bones and the reduction of the
mass of the brain; nerve cells are
altered ,impaired bone growth;
detected fibrosis of myocardium,
vessels of the meninges.
Gunther
disease
Dermatan sulfate
Iduronate
sulfatase
Due to mutation there is increased
synthesis of the pigment precursor of the porphyrin, which leads
to its increased content in the
erythrocytes (up to 25
times).Chronic photosensitivity. As a result of allocation of
excess pigment, the urine becomes blood-red color, increased
growth of body hair.
Sanfilippo
disease
Heparansulfate
Heparansulfate,
M-acetyl-αb-glucosaminidase or
acetyltransferase
Stunting, lungs, skeletal changes,
sometimes a small enlargement of
the liver and spleen, develops
convulsions.The disease is characterized by gross mental disturbances, mental retardation (dementia), rigidity of the joints.
Morquio
disease
Keratan overlays
Chondroitin-6sulfate
Chondroitin
sulfate –
N-acetylates Amin-6 sulfatesulfate
Characterized by dwarfism
(growth of the adult patient of
about 100 cm), disproportionate
body type (relatively short body,
microcephaly, short neck), coarse
facial features and significant deformation of the skeleton, especially of the chest (chicken, barrel, pigeon), kyphosis or scoliosis
of the thoracic and lumbar
spine.Stiffness in the joints.
sosomal hydrolases. As these diseases are not currently curable, it is necessary to
carry out prenatal diagnosis in cases of suspected carriers of the defective genes.
Types of mucopolysaccharidoses
Sly's
disease
Chondroitinsulfate
β-glucuronidase
Inguinal and umbilical hernia,
low rise, keeled chest, thoracolumbar kyphosis, clubfoot, recurrent pulmonary infection. Typical coarse facial features with sunken nose bridge,
nostrils turned forward.Perhaps
the development of cardiomyopathy, hypertension.
MarotoLamy
disease
Dermatan sulfate
Chondroitin
sulfate –
N-acetilgalaktozamin-4sulfatesulfate
Characterized by stunted growth,
coarse facial features, small upper
jaw, short neck, barrel chest,
shorter clavicle.Marked flexion
contractures of the joints of the
upper extremities (patients cannot
hands up); age there are contractures in the joints of the lower
limbs, the gait is disturbed. Often
with acute respiratory viral infections.
Malabsorption – a group of diseases associated with the violation:
1) digestion of carbohydrates in the digestive tract (defect of enzymes);
2) malabsorption of degradation products of monosaccharides.
An example of the first group of diseases is hypertension (disaccharides).
In children there are 2 forms:
– transient (up to year of life) associated with immaturity of the enzyme lactase;
– genetic – mutation in the gene responsible for the synthesis of the enzyme lactase.
Adults:
– defect of lactase because the gene expression of lactase
the age of the character, while a milk intolerance is more common in people of
African and Asian descent. The average frequency of this form of the disease in
Europe – 7–12 %, and in China 80 % in parts of Africa and 97 % (historically a diet);
acquired character – intestinal diseases (gastritis, colitis, enteritis). As is known,
the activity of lactase is lower than other disaccharidases, therefore, the decrease in
its activity becomes more noticeable.
In all cases, there is osmotic diarrhea, which is caused by unsplit unabsorbed
disaccharides and monosaccharaides, entering the distal intestine. They change the
osmotic pressure, is partially subjected to enzymatic cleavage by microorganisms
with the formation of acids, gases, enhanced by the inflow of water into the intestine, increasing the volume of intestinal content, increases peristalsis, appear flatulence and pain.
1.13. Standards of solving tasks
CH2OHCHOH2C
O
OH
H
H
OH
H
OH
O
OH
H
H
H
OH
OH
H OH
H
CH2OH
1
2
3
4
5
6
C
CH2OH
O
H OH
OH H
H OH
H OH
H
1. Give the name to the given monosaccharide:
Solution: This monosaccharide contains a chain of six carbon atoms, three of
which are chiral, and one keto-group. The particular location of the hydroxyl groups
at carbon atoms C-3, C-4 and C-5 indicate that the monosaccharide is
D-fructose.
2. For monosaccharide, presented in the form:
1) specify the possible forms in which it can exist in solution;
2) discuss the possibility of the formation of cyclic forms with the participation
of the hydroxyl groups at C-2 and C-3;
3) determine what form represented by the formula;
4) bring an open form of the monosaccharide and name it.
Solution: 1) In aqueous and ethanol solutions, this monosaccharide exists simultaneously in the open form (axiome) and cyclic forms furanose (α and β) and
pyranose (α and β), which are formed due to the interaction of the respective hydroxyl groups and aldehyde groups of the monosaccharide;
2) a cyclic form involving hydroxyl groups at C-2 and C-3 are not formed,
since the resulting three - and four-membered cycles of intermittent;
3) this formula corresponds to α-D-pyranose form;
4) given circular form corresponds to the following open form:
and C-5 indicate that the monosaccharide is D-glucose.
The particular location of the hydroxyl groups at carbon atoms C-2, C-3, C-4
3. Bring all forms in which there is glucose in an aqueous solution, and name
C
CH2OH
O
H OH
OH H
H OH
H OH
H
H2OH2O
O
H
H
OH
H
OH
H OH
CH2OH
H
OH
+
O
H
H
OH
H
OH
H OH
CH2OH
OH
H
I
II
O
OH
H
H
OHH
OH
H
CH2OH
OH H
+
O
H
OH
H
OHH
OH
H
CH2OH
OH H
III
IV
O
H
H
OH
H
OH
H OH
CH2OH
OH
HCl
(сухой)
+ CH3OH
O
OCH
3
H
H
OH
H
OH
H OH
H
CH2OH
+
O
H
H
H
OH
H
OH
H OH
OCH
3
CH2OH
I II
them.
1) what type of reaction of formation of cyclic form?
2) What shape is produced?
3) what is the feature of monosaccharides to form in the solution of various
shapes?
4) what determines the ratio of the anomers in solution?
Solution: In aqueous solution D-glucose exists in the following forms:
The names of the resulting compounds: α-D-glucopyranose (I), β-D-glucopyranose (II), β-D-glucofuranose (III), α-D-glucofuranose (IV).
1) the Reaction of formation of cyclic form, is the intramolecular reaction of
cyclization.
2) In a solution of mostly monosaccharide pyranose forms are formed as ther-
modynamically more stable.
3) Feature of monosaccharides to form in solution various forms is called mu-
tarotase.
4) the Ratio of α - and β-anomers depends mainly on the nature of the solvent.
4. Draw a scheme of the reaction of galactose with methyl alcohol in the presence of dry HCl. Name the reaction product. Why the reaction proceeds only with
involvement of a certain hydroxyl group of the monosaccharide?
Solution:
Name the products of the reaction: methyl-α-D-galactopyranoside (I); methyl-
β-D-galactopyranoside (II).
The interaction of the reagent with only glycoside hydroxyl group due to the
high reactivity polyacetylene carbon atom s-1.
5. Draw a scheme of the reaction of a monosaccharide with alkyl halogen:
O
H
H
H
OH
OH
H OH
CH2OH
OH
O
H
H
H
OH
OH
H OH
CH2OH
OH
CH3I, KOH
O
H
H
O
H
OCH
3
H OCH
3
CH2OCH
3
CH
3
OCH
3
H
+
O
H
H
O
H
OCH
3
H OCH
3
CH2OCH
3
CH
3
H
OCH
3
I
II
O
H
OCH
3
H
OCH
3
CH2OCH
3
H
OCH
3
H2O, H
+
СH3OH
O
H
OH
H
OCH
3
H
OCH
3
CH2OCH
3
H
O
OH
H
H
OCH
3
H
OCH
3
CH2OCH
3
H
+
I
II
O
H
OCH
3
H
OCH
3
CH2OCH
3
H
OCH
3
Name the reaction products.
Solution:
The particular location of the hydroxyl groups in the carbon atoms C-2, C-3 and
C-4 indicate that the cyclic form corresponds to Dglucose, therefore, the main reaction products are: methyl-2,3,4,6-Tetra-O-methyl-α-D- glucopyranoside (I), and
methyl-2,3,4,6-Tetra-O-methyl-β-D -glucopyranoside (II).
Participation in reaction of all hydroxyl groups of the monosaccharide is due to
conditions of disease (alkaline environment) and the activity of carbocation CH
+
as
3
electrophile.
6. Draw the reaction scheme of hydrolysis of given mono saccharide and name
the reaction products:
Which group is subjected to hydrolysis and why?
Solution:
As the substrate in the reaction involved furanose form oxometalates D-ribose,
the products of the reaction have the following names: 2,3,5-tri-O-methyl-α-Dribofuranose (I) and 2,3,5-tri-O-methyl-β-D-ribofuranose (II).
Hydrolysis is subjected to only the methoxy group at C-1, which is due to in-
O
H
H
H
OH
OH
H OH
CH2OH
OH
(CH3COO)2O
O
O
OAc
H OAc
CH2OAc
Ac
H
OAc
H
H
+
O
O
OAc
H OAc
CH2OAc
Ac
OAc
H
H
H
H
I
II
CHO
CH2OH
H OH
OH H
H OH
H2/Pt
CH2OH
CH2OH
H OH
OH H
H OH
creased in comparison with other carbon atoms furanose cycle electrophilicity of
atom s-1, due to the influence of the neighboring atom of oxygen, exhibiting the
properties of electron acceptor.
7. Draw the reaction scheme of acetic anhydride with D-glucopyranose. Name
the reaction product.
Solution:
Name the reaction products: 1,2,3,4,6-penta-O-acyl-α-D-glucopyranose (I) and
1,2,3,4,6-penta-O-acyl-β-D-glucopyranose (II).
The acylation of all the hydroxyl groups in the pyranose cycle of
D-glucose caused by high ability of acetic anhydride.
8. Give a reaction scheme for the recovery of D-xylose hydrogen. Name the re-
action product.
Solution:
The name of the product of the reaction xylitol. The restoration is subjected to
a first aldehyde group, as carbonyl atom has a higher oxidation state (+2) than the
carbon atoms associated with hydroxyl groups (+1).
9. Give a scheme of the isomerization of glucose in dilute aqueous alkaline solution at room temperature. Name the reaction products. What is the role of environment?
Solution:
In dilute alkaline solutions at room temperature, isomerization occurs D-glucose,
which produces an equilibrium mixture of monosaccharaides that differ in configuration of atoms C-1 and C-2. Products of isomerization D-glucose are D-mannose (I)
and D-fructose (II).
Alkaline catalyzes the conversion D-glucose to en-diol form due to the high
mobility of the hydrogen atom at C-2 caused by the presenceof two substituents
groups aldehyde and hydroxyl.
10. What caused the formation of cyclic forms of sugars? What is the essence of
the phenomenon of saccharides mutarotation in the solution? Show this on the example of maltose. All mutarotase sugars in solution?
Solution: The formation of cyclic forms is associated with the ability of the hy-
drocarbon chains of the saccharide to make profitable chelatespatial conformation,
resulting aldehyde and the hydroxyl group are contiguous. The result of nucleophilic
attack of hydroxyl on the carbonyl carbon atom occur intramolecular cyclization
with the formation of an additional chiral center on the site of the atom-1, formerly
part of the carbonyl group. This atom is called the anomeric and two corresponding
stereoisomer α- and β-anomers.
Thus, the essence of the phenomenon of mutarotation lies in the fact that many
sugars exist in solution simultaneously in two forms open and cyclical, resulting
in α- and β-anomers:
Mutarotase in the solution are subjected to monosaccharides, and some disaccharides, which are composed of a glycoside bond to the hydroxyl group not
involved in the formation of a glycosidic bond. These are called reducing disaccharides (lactose, maltose, and cellobiose, etc.).
In non-reducing disaccharides glycosidic bond formed by the hydroxyl groups
in anomeric carbon atoms. They polyacetale no free hydroxyl groups, therefore, the
solutions of these disaccharides, such as sucrose, do not mutarotate.
Questions for self-control
1. What sugar is part of most polysaccharides?
2. Which of the carbohydrates do not undergo hydrolysis?
3. What forms exist in solution monosaccharides?
4. What caused a large number of stereoisomers in monosaccharides?
5. Why glycosides do not possess reducing properties?
6. Why the glycosides are hydrolyzed by dilute aqueous acid solutions, but sta-
ble to hydrolysis in an alkaline environment?
7. What caused the increased reactivity of glycoside hydroxyl?
8. What caused the larger amount in solution pyranose forms of monosaccha-
rides compared to furanoses?
9. Give examples of reducing and non-reducing disaccharides. How do they dif-
fer in chemical structure?
10. What compounds are formed by the hydrolysis of glycosides?
11. How to make stereospecific hydrolytic cleavage of α - and β-glycosides?
12. With the help of what reagent it is possible to prove the restorative proper-
ties of cellobiose?
13. What reagents are used to detect ketosis?
14. Is it possible to detect glycosides using reagent Benedict's and Fehling's?
15. What is formed by mutarotation solutions of monosaccharides?
16. What monosaccharides and where do they occur in free form?
17. What is the disaccharide found in milk and what is manifest its beneficial
properties to humans at an early age?
18. As used cellulose and its derivatives?
19. How to use the glucose in clinical practice?
20. In any plant contains significant amount of sucrose?
21. What are the derivatives of carbohydrates are effective means to treat heart
disease?
Situational task on the theme «Carbohydrates»
Task 1. What are the disaccharides can be formed from glycogen in its digestion
in the gastrointestinal tract? List the enzymes acting on glycogen in the gastrointestinal tract. Write the formulas of disaccharides.
Task 2. During strenuous work the muscle tissue consumes much more ATP
than at rest. It is known that in white skeletal muscle, e.g. in the leg muscles of a
rabbit or Turkey, almost the whole ATP is formed during anaerobic glycolysis.Could work stress muscle, with great speed to form ATP by glycolysis, if there
was no enzyme lactate dehydrogenase? Explain your answer.
Task 3.
In a graph shows the relationship between the concentration of ATP and activity of phosphofructokinase, which is an allosteric enzyme. Phosphofructokinase
activity with increasing ATP concentration first increases, but at some point, a turning point – a further increase in the concentration of ATP causes inhibition of the
Соседние файлы в предмете [НЕСОРТИРОВАННОЕ]