Добавил:
ivanov666
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Carbohydrates. Bioenergetics. Study manual
.pdf
The non-oxidative pathway involves transfer reactions of 2- and 3-carbon fragments from one molecule to another. This path is used for synthesis of pentose. The
process is reversible, and the pentose may be formed of hexoses.
Pentose phosphate pathway the pentose education takes place in the liver, adipose tissue, mammary gland, adrenal cortex, erythrocytes.
The main stages of pentose phosphate pathway ways of oxidation of glucose include the following processes:
1) dehydrogenation of glucose-6-phosphate, with the participation of glucose-6phosphate dehydrogenaseand coenzyme NADP+with the formation of 6phosphogluconate-d-lactone and NADPH:
2) 6-phosphogluconate-d-lactone is unstable and is hydrolyzed to form 6-phosphogluconate (enzyme – 6-phosphogluconolactonase):
3) the dehydrogenation and decarboxylation of 6-phosphogluconate education
ribulose-5-phosphate (pentose) and NADPH with the participation decarboxylase
6-phosphogluconolactonase:
4) under the influence of isomerase ribulose-5-phosphate is converted into ribose-5-phosphate (pentose).
At this stage of the pentose phosphate pathway can be completed. Under other
circumstances comes non-oxidative stage of the pentose phosphate cycle, occurring
under anaerobic conditions. It is the transfer of two - and three-carbon fragments
from one molecule to another. In this form the substance characteristic of glycolysis
(fructose-6-phosphate, fructose-1,6-bisphosphate, posttreaty), and substances that
are specific to pentose phosphate pathway way (sedoheptulose-7-phosphate, pentose-5-phosphate, erythrose-4-phosphate).
Six molecules of glucose-6-phosphate in pentose phosphate pathway form
6 molecules ribulozo-5-phosphate and 6 molecules FADH2. Of the 6 molecules
ribulozo-5-phosphate is regenerated by 5 molecules of glucose-6-phosphate. Intermediate products of cycle (fructose-6-phosphate and glyceraldehyde-3-phosphate)
are involved in glycolysis.
1.9. Gluconeogenesis
Gluconeogenesis is the biosynthesis of glucose from non-carbohydrate compounds of different nature. The biological role of gluconeogenesis is to maintain a
constant level of glucose in the blood, which is necessary for normal energy supply
of the tissues, which are characterized by a continuous need of carbohydrates. This
is especially true of the central nervous system.
The role of gluconeogenesis is increased if insufficient intake of carbohydrates
with food. So, in the body of a starving human can be synthesized up to 200 g of glucose per day. Gluconeogenesis faster than other metabolic processes responds to
changes in the diet: introduction high dietary intake of proteins and fats, activates a gluconeogenesis; excess carbohydrates, in contrast, inhibits the new formation of glucose.
Intense physical loads are accompanied by rapid depletion of glucose in the
body. In this case, gluconeogenesis is the major route of carbohydrate replenishment
resources, preventing the development of hypoglycemia. Gluconeogenesis in the
body is closely connected also with the processes of neutralization of ammonia and
the maintenance of acid-base balance.
The main site of biosynthesis of glucose de novo it is the liver. Gluconeogenesis
also occurs in the cortical layer of the kidneys and the cells of the intestinal mucosa. It is considered that the contribution of the kidney in gluconeogenesis under
physiological conditions is about 10% of the glucose synthesized in the body; in
pathological conditions, this percentage may increase significantly. Little activity of
the enzymes of gluconeogenesis found in the mucosa of the small intestine.
The reaction sequence in gluconeogenesis is the application of the corresponding reaction of glycolysis. Only three reactions of glycolysis are irreversible due to
what is happening in the course of their significant energy shifts:
a) phosphorylation of glucose;
b) phosphorylation of fructose-6-phosphate;
c) in turning phosphoenolpyruvate to pyruvate.
Bypass these energy barriers provide key enzymes of gluconeogenesis.
The reverse transformation of pyruvate to phosphoenolpyruvate requires the
participation of two enzymes. The first of them pyruvate carboxylase - catalyzes the
reaction of formation of oxaloacetate (reaction 1)Pyruvate carboxylase the coenzyme is Biotin (vitamin H). The reaction proceeds in the mitochondria. Its role is
also to replenishment of oxaloacetate for the Krebs cycle.
All subsequent reactions of gluconeogenesis occur in the cytoplasm. The mitochondrial membrane is impermeable to oxaloacetate, and it is transferred into the cytoplasm in the form of other metabolites: malate or aspartate. In the cytoplasm of
these compounds are again transferred to the oxaloacetate. With the participation
of phosphoenolpyruvate carboxylase from the oxaloacetate formed phosphoenolpyruvate (reaction 2).
Phosphoenolpyruvate a result of the treatment of a number of reactions of glycolysis passes into fructose-1,6-diphosphate. The conversion of fructose-1,6-diphosphate into
fructose-6-phosphate is catalyzed byfructosediphosphatase (reaction 3).
Fructose-6-phosphate isomerized in glucose-6-phosphate. The final reaction of
gluconeogenesis is the hydrolysis of glucose-6-phosphate with the enzyme glucose6-phosphatase (reaction 4).
The bypass reaction of gluconeogenesis
The main sources of glucose in gluconeogenesis are lactate, amino acids, glycerol, and metabolites of the Krebs cycle.
Glucose-lactate cycle (Cori cycle)
Lactate the end product of anaerobic glucose oxidation in muscles, especially in
white muscle fibers, where mitochondria are smaller than in the red. May be involved in gluconeogenesis after oxidation to pyruvate in lactate dehydrogenase reaction. Long the main source of lactate is the skeletal muscles, in the cells which is
dominated by anaerobic processes. The accumulation of lactic acid in the muscles
limits their performance. This is because when the concentration of lactic acid in the
tissues decreases the pH (lactic acidosis). The variation of pH leads to inhibition of
important enzymes of metabolic pathways. In the disposal of the produced lactic
acid has an important role glucose-lactate cycle of Cori.
The Cori cycle and glucose-alanine cycle (explanation in text)
aminoacids
Lactate formed in muscles is transferred by the blood to the liver, where gluconeogenesis is converted into glucose, which the blood can return to the working
muscles. In the liver a part of lactate can be oxidized to carbon dioxide and water to
turn into pyruvate and be involved in the General way of catabolism.
The value of the Cori cycle:
1. Regulation of a constant level of glucose in the blood.
2. Ensures utilization of lactate.
3. Prevents the accumulation of lactate (reduction in pH lactic acidosis).
4. Economical utilization of carbohydrates by the body.
Regulation of carbohydrate metabolism at the levels of tissues – blood, liver,
muscles.
Glucogenic amino acids, which include the majority of protein amino acids. The leading role in gluconeogenesis among amino acids belongs the alanine that
can turn into pyruvate by transamination. When fasting, physical work, and other
conditions in the body functioning glucose-alanine cycle like Cori cycle for lactate
figure 16.2. The existence of a cycle alanine – glucose prevents the poisoning of the
body as in the muscles, no enzymes capable of degrading ammonia. As a result of
training the power of this cycle is greatly increased.
Can other amino acids, like alanine, turn into pyruvate and in intermediate
products of the Krebs cycle (α-ketoglutarate, fumarate, succinyl-CoA). All these metabolites can be converted to oxaloacetate and enter into gluconeogenesis.
Glycerol – the hydrolysis product of lipids in adipose tissue. This process is
greatly enhanced when fasting. In the liver glycerol is converted into dioxyacetone
phosphate is an intermediate product of glycolysis and can be used in gluconeogenesis.
Fatty acids and acetyl-CoA not are the precursors of glucose. The oxidation of
these compounds provides energy for the synthesis of glucose.
Energy balance. The path of synthesis of glucose from pyruvate figure 16.6
contains three reactions are accompanied by consumption of ATP or GTP:
a) formation of oxaloacetate from pyruvate (a molecule of ATP is expended);
b) the formation of phosphoenolpyruvate from oxaloacetate (requires GTP
molecule);
c) contacting the first substrate phosphorylation – the formation of 1,3-diphosphoglycerate 3-phosphoglycerate (takes a molecule of ATP).
Each of these reactions is repeated twice, as for the formation of 1 molecule of
glucose (C6) using 2 molecules of pyruvate (C3). Therefore, the energy balance of
the synthesis of glucose from pyruvate is 6 molecules of nucleoside triphosphates
(4 molecules of ATP and 2 molecules of GTP). When using other precursors and
energy balance of the biosynthesis of glucose is different.
1.10. Glycogen. The breakdown and glycogen synthesis
Glycogen – intracellular, osmotically inactive reserve polysaccharide,capable of
rapid and reversible transformation into glucose. The process of decay is called glycogenolysis, the process of synthesis –glycogenesis. Glycogen – animal starch, the
main reserve homopolysaccharide. A significant portion of glucose entering the
blood is converted into glycogen – reserve polysaccharide used in the intervals between meals as a source of glucose. The highest concentration of glycogen is found
in liver 2–6 %, and muscle contains 0.5–2 %. In the cell glycogen is not in a dissolved state, and in the form of pellets. Glycogen has a high molecular weight
(1∙106–2∙108) and contains up to 1 million glucose residues connected by 1,4 and 1,6 –
glycoside bonds. Glycogen with iodine gives a red – brown staining.
Glycogen is a white powder, good soluble in water to form a colloidal solution. Glycogen, like proteins, has dramatically you incorporates hydrophilic properties, so it you can easily precipitate from solution during the salting out with salts of
alkali and alkaline earth metals, salts of heavy metals, alcohol. In the human liver
at normal diet 80–120 grams of stored glycogen. When fasting during the day, almost
the entire stock of glycogen is spent and cannot be detected by conventional qualitative reactions.
Glycogen is formed from UDP - glucose in the reaction catalyzed by glycogen
synthaseduring digestion for 1–2 hours after a meal. Especially intensively this process occurs in the liver and skeletal muscle. The necessity of conversion of glucose
into glycogen is that the accumulation of large amounts of glucose in the cell would
lead to increased osmotic pressure, since glucose is soluble in water substance. Glycogen is in a cage in the form of granules, and slightly soluble.
The process of glycogen synthesis – energy-intensive, for inclusion in the circuit one molecule glucose required 1 mol ATP and 1 mol of UTP.
Glycogenolysis. The reserve polysaccharide in human tissues is glycogen. The
process of glycogen breakdown – glycogenolysis, occurs between meals. This process can be carried out either by hydrolysis or phosphorolysis. Muscle glycogen is a
source of glucose for the cells, and the glycogen of the liver is to maintain physiological concentrations of glucose in the blood.
Phosphorolysisis the main mode of disintegration of glycogen, it catalyzes the
enzyme glycogenphosphorylase belonging to the class of transferases. Glycogenphosphorylase cleaves glucose residues under non-reducing end of the glycogen and
transfers them to a molecule of phosphoric acid with the formation of glucose-1phosphate:
Glucose-1-phosphate rapidly isomerized under the action of the enzyme
phosphoglucomutases, turning into glucose-6-phosphate, which is in the liver is hydrolyzed by phosphatase to glucose and phosphoric acid:
The process of phosphorylysis of glycogen finely adjustable. Regulation of activity of glycogen phosphorylase is a cascading nature, where you can select several
types of regulation of enzyme activity:
1) hormonal (glucagon in liver, epinephrine in muscle);
2) allosteric;
3) proteinkinase reaction (in this case, phosphorylation of serine side radical in
glycogen phosphorylase).
The activity of muscle phosphorylase is increased at a certain concentration of
AMP and acetylcholine, as well as in the presence of cations of calcium and sodium.
The rate of decline in pastoralize occurs with the decrease of the glycogen and
phosphoric acid, as well as an increase in the concentration of glucose-6phosphate. Mechanisms that reduce the speed of pastoralize of glycogen, prevents
the body from lot of expenditure carbohydrate reserves (glycogen), which could lead
to a lack of glucose necessary for the brain and heart muscle.
Hydrolysis of glycogen is catalyzed by the enzymes amylases, which belong to
the class of hydrolases. As a result of hydrolysis of the glycogen is broken down to
free glucose:
Hydrolytic breakdown of glycogen occurs normally in the liver. Glucose, obtained by hydrolysis of glycogen, it comes in a variety of tissues and organs of the
body, where it undergoes further disintegration.
1.11. Regulation of the level of glucose in the blood
Keeping the level of glucose in the blood and other tissues is neurohumoral system.
1. Autoregulation at the cellular level is carried out by allosteric mechanisms or
changes in the activity of enzymes, either by phosphorylation – dephosphorylation. For example, ATP and ADP are allosteric regulators of enzymes of glycolysis
and gluconeogenesis: high concentration of ATP activates the enzymes of gluconeogenesis, and a high ADP concentration activates key enzymes of glycolysis. High
concentration succinyl -CoA is a allosteric activator of the enzyme pyruvate carboxylases (many of succinic acid, the active TCA, gluconeogenesis is activated so
that requires expenditure of ATP from TCA).
2. Hormonal mechanism the regulation of carbohydrate metabolism is the
modification of enzyme activity through allosteric or by phosphorylation –
dephosphorylation of enzymes. The effect of hormones is realized with the participation of intermediaries, for example, c-AMP.
Adrenaline – hormone cerebral layer of the adrenal glands. The receptors for
adrenaline are contained in liver, adipose tissue and muscles. It has a hyperglycemic
effect through activation of glycogen breakdown.
Glucagon – pancreatic hormone with hyperglycemic activity. Glucagon in-
creases glycogen breakdown by activating pastoralize in the liver.
Hormones adrenaline and glucagon carry out its action according to the following scheme:
the increase in C-AMP increase in activity
protein kinase a increase activity of phosphorylase
the increase in the rate of glycogen breakdown into glucose.
Insulin – hormone of protein nature, produced by the pancreas. Has a hypogly-
cemic effect (decrease glucose in blood). Insulin activates the synthesis of active enzyme hexokinase and increases the permeability of cells to glucose. In the cells glucose is used for glycogen synthesis, and inhibited the process of glycogen breakdown and gluconeogenesis.
Corticotropin, somatotropin – pituitary gland hormones have hyperglycemic ef-
fects, i.e. increase the level of glucose in the blood.
Cortisone, cortisol (glucocorticoids) – hormones of the adrenal cortex. Target
organs are muscle, connective tissue, the liver. Have a hyperglycemic effect through
activation of gluconeogenesis.
Thyroxine, triiodothyronine the thyroid hormones. Have a hyperglycemic effect
through activation of gluconeogenesis.
1.12. Pathology of carbohydrate metabolism
The increase in the content of glucose in the blood – hyperglycemia can occur
due to excessive gluconeogenesis or as a result of lowering of the ability of glucose
utilization by tissues, for example in violation of the processes of its transport
through cell membranes.
The decrease in the content of blood glucose – hypoglycemia – may be a symptom of various diseases and pathological conditions, and are particularly vulnerable
in this respect is the brain: a consequence of hypoglycemia can be irreversible violation of its functions.
Genetically determined defects of the enzymes in carbohydrate metabolism are
the cause of many hereditary diseases. Example of genetically inherited disorders of
monosaccharide metabolism can serve as galactosemia developing in a result of
a defect in the synthesis of the enzyme galactose-1-phosphatidylserine. Signs of galactosemia also note the genetic defect UDP-glucose-4-epimerase. Characteristic features of galactosemia are hypoglycemia, galactosuria, the appearance and accumulation in the blood along with galactose galactose-1-phosphate and a decrease in body
weight, fatty degeneration and cirrhosis of the liver, jaundice, cataract, developing at
an early age, psychomotor development delay. In severe form of galactosemia children often die in the first year of life due to impaired liver function or reduced resistance to infection.
Соседние файлы в предмете [НЕСОРТИРОВАННОЕ]