FUNCTIONS OF BIOGENIC AMINES. AMMONIA FORMATION IN THE ORGANISM AND THE PATH OF ITS NEUTRALIZATION
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MINISTRY OF HEalt="FUNCTIONS OF BIOGENIC AMINES. AMMONIA FORMATION IN THE ORGANISM AND THE PATH OF ITS NEUTRALIZATION."H CARE OF THE REPUBLIC OF UZBEKISTAN
TASHKENT MEDICAL ACADEMY
The head of scientific methodological senate of Urgench branch of Tashkent Medical Academy the c.n.s. Yuldashev B.S.
«___» _____________ 2015
Department: Natural science
FUNCTIONS OF BIOGENIC AMINES. AMMONIA FORMATION IN THE ORGANISM AND THE PATH OF ITS NEUTRALIZATION.
Educational - methodical working out
(For teachers and students of medical Universities)
Composer: 1. S. Masharipov - professor, the chief of the department of natural
subjects of TMA Urgench branch
2. N.N.Kurbanova - senior teacher of the department of natural subjects
of TMA Urgench branch.
Reviewers: D. Dushamov - senior, candidate of chemical subjects, the director of
the third Academic Lyceum in Urgench State University.
B. Samandarova - assistant professor of department of skin-sexual and
infectious diseases, microbiology
Methodological manual was discussed in the meeting of scientific - methodological
senate ___ March 2015 year Protocol № __
Methodological manual was approved in the senate of TMA
. ___ March 2015 year Protocol № __
Scientific secretary, c.n.s docent N. Yu. Xudayberganov
Theme: Functions of biogenic amines. Ammonia formation in the organism and the path of its neutralization.
1. A place of carrying out of study, equipment:
- Department of Natural science, studying room;
- Evident posters and banners;
- Distributing stuffs;
- Panel of reagents;
- Panel of laboratory ware;
- Multimedia, overhead projector, PhEC, cuvette with 1 cm of thickness
2. Duration of studying of a theme:
- 4 hours.
3. Study purpose:
Explain to students importance of processes of decarboxylation of amino acids, functions of biogenic amines and a path of their neutralisation. Histaminum role in development of allergic and inflammatory reactions. Paths of formation and neutralisation of ammonia, the development cause of hyperammonemia. Use of the received knowledge in diagnostics and treatment of various pathologies.
Student should know:
- Decarboxylation of amino acids
- Functions of biogenic amines and a path of their neutralisation
- Histaminum, its role in development of allergic and inflammatory processes
- Antihistamine drugs
- Paths of neutralisation of ammonia
- Synthesis of urea and its connection with transamination reactions
- Disturbance of synthesis and removing of urea from an organism
- Hyperammonemia, its causes and a consequence
Student should be able:
To perform laboratory work - urea definition in blood serum.
Studying of function of biogenic amines, ammonia formation in an organism and a path of its neutralisation, hence, to study biochemical bases of development of diseases and methods of their treatment. Disturbance of these processes lead to morbid conditions. This knowledge for the future doctors of the general of a profile for statement of the diagnosis and diseases.
5. Communications between subject and inside subject:
Knowledge of composition and properties of a connective tissue, and also biosynthesis and pathologies bound to their changes is based on knowledge on bioorganic chemistry, physiology, anatomy, histology. This knowledge is necessary for mastering further such subjects, as pathological physiology, pharmacology, therapy, surgery, rheumatology, etc. clinical disciplines.
6. The employment maintenance.
6.1. Theoretical part.
Decarboxylation of amino acids and metabolism of biogenic amines
As a result of eliminating - carboxyl group of amino acids amines are formed. Products of this reaction are the biogenic amines possessing physiological activity. Thyrosinum, a tryptophan, 5-oksitriptofan, valine, a serine, Histidinum, a glutamate and scale-oksiglutamat, 3,4-oksifenilalanin, Cysteinum, an arginine, an ornithine, S-adenozilmetionin and an alpha-aminomalonat are exposed to decarboxylation. These are the complete reactions proceeding with participation of decarboxylases which coenzyme is Pyridoxalphosphatum. Decarboxylates possess a high biological potency and their name is bound to it - biogenic amines. We will bring some examples.
Biosynthesis of some neurotransmitters from amino acids. The key step is the same in each case: a PLP-dependant decarboxylation (shaded in pink).
Distinguish 4 phylums of decarboxylation of amino acids:
1. Alpha decarboxylation - significant for animal tissues. Thus there is an eliminating of the carboxyl group located close in alpha carbon atom. Products of the yielded reaction are СО2 and biogenic amines.
2. Omego-decarboxylation - significant for microorganisms. For example, this path decarboxylation of aspartic acid to alpha lactamic acid proceeds.
3. Decarboxylation with a transamination. In the yielded reaction new amino acid and aldehyde is formed.
4. Decarboxylation by condensation of two moleculas. In animal tissues sigma-aminolevulinic acid, sphingolipids, in plants biotin synthesis are formed of glycine and succinyl-KoA.
Formation of Histaminum and its importance. Histaminum is formed in reaction of decarboxylation of Histidinum in mast cells. Precipitates out in reply to allergen presence.
Physiological role of Histaminum:
Dilating of arterioles and capillars that leads to depression of arterial pressure;
Rising of permeability of capillars;
Originating of an intracranial hypertensia and a headache, owing to a trichangiectasia of a brain and exudation of a liquid part of a blood;
Reduction of a smooth musculation of bronchi and bronchospasm development;
The raised formation of a gastric juice and a saliva.
Importance of biogenic amines in development of allergic responses.
At a sensibilization antigens (proteinaceous and polysaccharide nature, some medicines) from mast cells Histaminum participating in development of allergic responses precipitates out. In some minutes at repeated entering of the conforming antigen an acute anaphylaxis. Exhaust of Histaminum by mast cells is bound by presence in their membrane of specific receptors and antigen-antibody complex formations.
For prophylaxis and treatment of allergic responses antihistamine drugs are widely used: Sanorinum, Pipolphenum, Dimedrol, glucocorticoids, etc.
Serotonin is formed as a result of decarboxylation 5- oxytryptophan by participation of ferment 5 - oxytryptophandecarboxylase.
Narrowing of a lumen of veins and development of an arterial hypertensia;
thermoregulation, regulation of activity of respiratory system, a glomerular filtration;
Promotes development of allergic responses, a dempink-syndrome, toxicoses of pregnant women, a carcinoid syndrome and a hemorrhagic diathesis.
Serotonin is formed of a tryptophan in hypothalamus neurones. Functions as probable neurotransmitter with the exciting character.
Gamma-aminobutyric acid (GABA) is formed in a brain tissue from glutamate at participation glutamatedecarboxylase. In synapses cerebrum and spinal cord concentration of GABA and glycine is high. GABA and glycine carry out functions brake neurotransmitter.
Dofaminum is formed of Thyrosinum in kidney, adrenals, synaptic ganglions, nerves. Is a mediator of inhibiting phylum, functions in a black substance of the top department of a brainstem. In other cells is the precursor of Noradrenalinum and adrenaline.
Noradrenalinum is formed as a result of Dofaminum hydroxylation in cells of the excitatory tissue, marrow of adrenals. Functions as a mediator in synaptic transfer of nervous impulses.
Adrenaline - a product of a methylation of Noradrenalinum in cells of marrow of adrenals. Carries out hormone functions.
The inactivation of biogenic amines descends by their deamination and oxidation. Neutralisation of biogenic amines is carried out by an oxidative deamination with aldehyde and ammonia formation at participation monoamine oxidase (MAO) and diamine oxidase (DAO).
MAO - its coenzyme is FAD, is localised in a choronomic membrane of mitochondrions, participates in neutralisation primary, secondary and tertiary amines. MAO can be a point of influence of some medicines inhibiting or activating this ferment as change of concentration of biogenic amines is at the bottom of some morbid conditions. For example, at a parkinsonism decrease of amount of Dofaminum is observed, and one of treatment methods is depression of rate of an inactivation of Dofaminum under the influence of materials-inhibitors MAO.
DAO - a coenzyme Pyridoxalphosphatum, it is localised in a cytoplasma, participates in neutralisation of Histaminum, putrescin, a cadaverine and particulate aliphatic amines.
The formed aldehydes at participation aldehyde dehydrogenaseacidify to organic acids.
Paths of formation of ammonia in organism:
1. Deamination of amino acids;
2. Deamination of biogenic amines;
3. Deamination of purine bases;
4. Disintegration pyrimidine bases;
5. Deamination of amidums of amino acids (asparagine and a glutamine).
For 1 days at scission of protein of 100 g 19,4 g of ammonia are formed. In tissues ammonia contains in low concentration and is in a kind ammonium ion (NH4 +). In a blood its content-25-40 mkmol/l (0,4-0,7 mg/l). High concentration of ammonia are toxic, especially for the excitatory cells clinically displayed in a pernicious vomiting, excitation, a coma. Formed at a deamination of amino acids ammonia (at physiological importance рН ammonia is in a kind of ions of ammonium) is toxic and should be removed from an organism. The ammonium ion can join directly in biological moleculas in several ways.
Paths of neutralisation of ammonia:
1. Formation of ammonium salts of organic acids;
2. Formation of amidums of amino acids;
4. Creatinine synthesis;
5. Urea synthesis;
6. Formation of ammonium salts.
Ammonium salts of organic acids: ammonium Citras, ammonium Sodium oxalatum, ammonium fumarate.
Asparagine and glutamine formation. They are the transport form of ammonia. Aspartic and glutamic acids at participation asparagine synthase, glutamine synthase and ATP attach ammonia to the first carbon atom. Most activly these reactions proceed in a liver and kidney.
L-aspartate + ATP + NH3 → L-asparagine + AMP + Н3РО4
L-glutamate + ATP + NH3→ L-glutamine + AMP + Н3РО4
Formation ammonium salts. In kidney asparagine and a glutamine under the influence of asparaginase and a glutaminase decompose, the formed ammonia forms ammonium salts.
L-aspargin + Н2О → L-aspartate + NН3
L-glutamine + Н2О → L-glutamat + NН3
NH3 + H + + Cl→ NH4Cl
In kidney they provide acid-base equilibrium maintenance, prevent development of an acidosis and loss of ions of sodium. This path decontaminates 0,3-0,4 g of ammonia.
The ammonia part in tissues is used for synthesis of new amino acids (retransamination).
About 15 % of ammonia it is used for synthesis of a creatinine by a transmethylation. This process proceeds in 3 tissues: kidney, muscles and a liver, with the assistance of 3 amino acids: an arginine, glycine and methionine.
1. arginine+glycine - glycine-amidinotransferaza - guanidine acetate(glycociamine) and an ornithine. Proceeds in kidneys and pancreas.
2. guanidine acetate + S-adenozilmetionin - a methyltransferase - a creatine. Proceeds in a liver and a pancreas.
3. kreatine+ATP - creatinephospho kinase- a creatine phosphate. Proceeds in muscles.
4. A creatine phosphate dephosphorylization - a creatinine.
About 2 % of a creatine in an organism turns to a creatinine. In muscles creatine level - 25-55 g/kg, in a cardiac muscle - 15-30 g/kg, in a brain tissue - 10-15/kg the Creatine precipitates out with urine only at children, at adults for 1 days 4,4-17,6 mmol/days precipitate out with urine there Is a certain connection between muscular mass and creatinine allocation. Presence in urine of a creatine and activity depression creatinephospho kinase in muscles testify about development of a dystrophia of muscles.
About 85 % of ammonia it is decontaminated in a liver in ornithinic cycle. Urea synthesis - cyclic process consists of five reactions, catalyzed by five separate ferments. The overall equation:
Ornithine cycle is bound to a tricarbonic acid cycle through fumarate.
Fumarate - malat - oxaloacetate- asparagine.
1 atom of nitrogen - at the expense of ammonia, 2 atom - aspartate amino groups.
From the analysis of process of synthesis of urea follows:
Nitrogen including descends in two points. One of atoms of nitrogen arrives in the form of NH3 in reaction 1 and is a product of a deamination of amino acids, and another joins as a part of aspartate (reaction 3). This second nitrogen can arrive in aspartate from any amino acid by a transamination with oxaloacetate. Hence, atoms of nitrogen in urea have a different parentage;
Ornithine cycle is bound to a citrate cycle as oxaloacetate, necessary for a transamination, it is formed of fumarate in reactions of a citrate cycle;
Process endergonic, demanding 3 mole АТР for synthesis of one molecula of urea.
At insufficient activity ferments Ornithine cycle arise hyperammonemia- morbid conditions accompanied by ammonia strengthening in a blood.
Disturbances of synthesis of urea:
1. The Chronic hepatitis and a cirrhosis. At these diseases are essentially broken the basic functions of hepatocytes, including urea synthesis.
Ornitin-karbamoil-transferase - hyperammonemia;
argininosuccinat synthase- citrullinuria;
argininosuccinat lyase- argininosuccinaturia.
Disturbance of metabolic processes.
In blood serum the filtrate nitrogen compounds 15-25 mmol/l. From them:
40-50 % - an urea nitrogen,
25 % - nitrogen of amino acids,
8 % - ergotionin,
4 % - uric acid,
5 % - a creatine,
2,5 % - a creatinine,
0,5 % - an indican and ammonia.
Filtrate nitrogen rising is called hyperammonemia.
At disturbance of function of nephroses urea level increases in blood serum to 50-80 mm/l, at norm - 3,5-9,0 mm/l.
At a liver hyperammonemia pathology is bound to augmentation of ammonia in level.
Urea cycle and reactions that feed amino groups into the cycle. The enzymes catalyzing these reactions (named in the text) are distributed between the mitochondrial matrix and the cytosol. One amino group enters the urea cycle as carbamoyl phosphate, formed in the matrix; the other enters as aspartate, formed in the matrix by transamination of oxaloacetato and glutamate, catalyzed by aspartate aminotransferase. The urea cycle consists of four steps. (1) Formation of citrulline from ornithine and carbamoyl phosphate (entry of the first amino group); the citrulline passes into the cytosol. (2) Formation of argininosuccinate through a citrullyn-AMP intermediate (entry of the second amino group). (5) Formation of arginine from argininosuccinate; this reaction releases fumarate, which enters the citric acid cycle. (A) Formation of urea; this reaction also regenerates ornithine.
New pedagogical technologies used on employment:
Scenario: one theme and students gets out express the opinions on the yielded theme. The secretary is prescribed. Similar thoughts are united. 5-7 minutes are yielded. In the end the most interesting answers precipitate out and estimate. The bad evaluation is not yielded.
This method promotes development of speech, thinking of the student.
Questions of an interactive method:
Importance of decarboxylation of amino acids, functions of biogenic amines and a path of their neutralisation.
Histaminum, its role in development of allergic and inflammatory reactions.
Paths of formation of ammonia.
Paths of neutralisation of ammonia
Synthesis of urea and its connection with transamination reactions.
Disturbance of synthesis and removing of urea from an organism.
Hyperammonemia, its causes and a consequence.
6.2. An analytical part
1. In an out-patient department the patient with complaints to a various enanthesis and other allergic implications has reverted. To what disturbance of an exchange of amino acids it is bound? What biogenic amine and what ferment is necessary for defining for statement of the correct diagnosis? Tactics of treatment of the doctor?
2. At the patient to blood serum the high content of ions of ammonium and the depressed level urea is defined. What tactics of the doctor? What kind hyperammonemia? The development cause hyperammonemia? Treatment principles?
1. One of the general paths of a catabolism of amino acids is decarboxylation.
What bonds are thus formed:
Catalyze these reactions:
Coenzyme these enzymes are:
2. Biogenic amines in an organism are decontaminated.
What bonds are thus formed:
Ketones and amines
Aldehydes and ammonia*
Ammonia and alpha ketonic acids
Ammonia and dioxides
Aldehydes and amines
These reactions catalyze:
monoamino - And di oxidase*
monoamine oxidase and hydrolyzing enzymes
diamine oxidaseand dehydrogenases
monoamine oxidase and hydratases
hydrolysis and dehydrogenases
Specify coenzymes MAO and DAO:
MAO - Pyridoxalphosphatum, DAO - a thiamine pyrophosphate
MAO - a thiamine pyrophosphate, DAO - Pyridoxalphosphatum
MAO - FAD, DAO - FMN
MAO - FAD, DAO - Pyridoxalphosphatum*
MAO - Pyridoxalphosphatum, DAO - FAD
3. There are 4 kinds of decarboxylation of amino acids:
Omega - decarboxylation *
Decarboxylation which has been not bound to a deamination
Decarboxylation bound with transamination*
Decarboxylation bound to a deamination
betta - Decarboxylation
Decarboxylation bound with molecular condensation*
Scale - decarboxylation
4. Specify 3 representatives of the biogenic amines formed as a result of decarboxylation of aromatic amino acids:
5. Specify 5 physiological properties of Histaminum:
Rising of arterial pressure
Dilating vascular vessels*
Permeability rising capillary*
Depression of permeability of capillars
Rising of an intracranial pressure and appearance of headache*
Intensifying of production of hydrochloric acid in stomach*
Oppresses production of НСl in stomach
Participates in development allergic reactions*
Does not cause an allergy
Reduces a smooth musculation
6. Specify 5 physiological properties of a serotonin:
Depresses arterial pressure
Promotes occurrence of bronchismus*
Relaxs muscles of bronchi
Causes an intestine atony
Raises a peristalsis of intestines*
Relaxs a smooth musculation of pots
Possesses antidiuretic effect*
Raises synthesis НСl in a stomach
7. Specify 3 representatives of catecholamins:
8. Specify 3 paths of neutralisation of biogenic amines:
In a liver by conjugation*
9. Specify 3 paths of formation of ammonia to an organism.
Deamination of amino acids*
Transamination of amino acids
Deamination of nucleotides*
Decarboxylation of amino acids
Reamination of amino acids
Deamination of biogenic amines*
10. Specify 4 paths of neutralisation of ammonia:
Participation in synthesis of carbohydrates
Participation in asparagine synthesis of glutamin*
Participation in synthesis of lipids
Participation in reactions reamination of amino acids*
Participation in heme synthesis
Participation in synthesis of urea*
Participation in synthesis of nucleotides
Formation of ammonium salt*
11. Specify 5 ferments of ornithine cycle:
Carbomoil phosphate synthetase*
12. Specify 3 organs participating in synthesis of a creatinine:
13. Specify 3 amino acids participating in synthesis of a creatinine:
6.3. Practical part
Laboratory works on an employment theme:
Definition of the content of urea in blood serum.
Purpose: to Master skills of definition of urea in blood serum.
Carried out stages (steps):
Completely correctly executed
To take 2 rotary tubes. In the first to pour 0,8 ml distilled water, 0,2 ml of blood serum and 1 ml of 10 % THUK, mix.
In the second tube (control) to pour 0,8 ml distilled water, 0,2 ml of standard solution of urea and 1 ml of 10 % THUK, mix.
In 15 minutes of the tube to centrifuge during 10 mines at 1500 circulation/minutes
To take from each tube on 0,5 ml above precipitate in pure tubes and to add 0,5 ml of colour reagent, to agitate.
Contents of tubes to hydrolyze during 20 mines in a boiling water bath, to cool running water.
Intensity of a staining of solutions colorimetric evaluate on FEC at a green light filter in a ditch with length of a path 10 mm against control.
To calculate the content of urea with use of the conforming formula
The analysis of the received results
7. Forms of control of knowledge, skills and abilities:
- The oral;
- The written;
- The decision of situational problems;
- Demonstration of the mastered practical skills.
8. Criteria of an evaluation of monitoring.
Progress in %
Level of knowledge of the student
The student has completely answered all questions set by the teacher. Completely can explain decarboxylating amino acids, function of biogenic amines and a path of their neutralisation. Histaminum, its role in development of allergic and inflammatory processes. Antihistamine drugs. Paths of neutralisation of ammonia, synthesis of urea and its connection with transamination reactions. Disturbance of synthesis and removing of urea from an organism. hyperammonemia, its causes and a consequence.
Independently sums up and makes decisions, creatively thinks. Correctly and creatively the decision of situational problems makes, the answer proves. Creatively takes part in interactive methods of education, does correct and substantiated conclusions. Actively participates in laboratory works, independently does a conclusion. Can prepare the indicative abstract of a high level, using the modern information or the literature of last years, or incorporates till 7-10 the Internet information.
The student correctly and precisely answers the asked questions of the teacher. Independently also can creatively explain the mechanism. On situational problems yields the exact answer, perceives its sense. In interactive games participates actively. Can prepare the indicative abstract of a high level, using the modern information or the literature of last years, or incorporates till 7-10 the Internet information. Uses the collected knowledge during employment for performance of laboratory works.
The student answers all questions set by the teacher. Knows the mechanism of decarboxylating amino acids, function of biogenic amines and a path of their neutralization. Histaminum, its role in development of allergic and inflammatory processes. Antihistamine drugs. Paths of neutralization of ammonia, synthesis of urea and its connection with transamination reactions. Disturbance of synthesis and removing of urea from an organism. hyperammonemia, its causes and a consequence.
Independently and logically thinks about its importance. Situational problems answers by means of the teacher, but knows its reserving. In interactive games participates actively and creatively. Can prepare the indicative abstract of a high level, using the modern information or the literature of last years, or incorporates till 7-10 the Internet information. Uses the collected knowledge during employment for performance of laboratory works.
The student answers all questions set by the teacher, but supposes thus discrepancies. Knows the mechanism Histaminum, its role in development of allergic and inflammatory processes. Antihistamine drugs. Paths of neutralization of ammonia, synthesis of urea and its connection with transamination reactions. Disturbance of synthesis and removing of urea from an organism.
Answers questions of situational problems. Actively participates in interactive games. Can prepare the indicative abstract of a high level, using the modern information or the literature of last years, or incorporates to 5-6 information of the Internet. Uses the collected knowledge during employment for performance of laboratory works.
The student answers the questions set by the teacher, but supposes discrepancies. Knows the mechanism of a path of neutralization of ammonia, synthesis of urea and its connection with transamination reactions. Disturbance of synthesis and removing of urea from an organism. Hyperammonemia, its causes of a consequence.
At the answer to questions of situational problems is at a loss. Actively and creatively approaches to participation in interactive games. Can prepare the indicative abstract of a high level, using the modern information or the literature of last years, or incorporates to 3-4 information of the Internet. Can perform laboratory works.
The student answers not all questions of the teacher. Can explain the mechanism of the Path of neutralization of ammonia, synthesis of urea and its connection with transamination reactions. Antihistamine drugs. Hyperammonemia, its causes and a consequence. Answers questions of situational problems, but does not perceive its sense. Participates in interactive games. Can prepare the indicative abstract, using the modern information or the literature of last years, or incorporates to 1-2 information of the Internet. Knows sequence of performance of laboratory works.
The student not completely answers questions of the teacher. Is at a loss at the answer to questions of situational problems. Passively participates in interactive games. Does not perceive sense. Finds it difficult to explain them.
The student not completely answers questions. Cannot explain independently, does not perceive their sense. Finds it difficult to answer questions of situational problems, does not perceive its sense. Is at a loss in summarizing of laboratory works.
The student not completely answers questions. Independently and logically does not perceive the mechanism to a theme. Cannot answer questions of situational problems. Cannot explain sequence of carrying out of laboratory works.
54 and more low
The student does not know a theme, is at a loss in performance of laboratory works.
9. Chronological card of activity.
Parenthesis of the teacher (theme substantiation)
Discussion of a theme of laboratory research, evaluation of initial knowledge of students with use of new pedagogical technologies
Oral poll, explanation, discussion
Carrying out of results of discussion
Representation of indicatings, tasks on performance of laboratory works, an explanation of veneering of the report of the performed work
Independent work of students on mastering of practical skills
Performance of laboratory work
Finding-out of degree of achievement of the purpose of study on the basis of the mastered theoretical knowledge both by results of practical work and taking into account it an evaluation of activity of bunch.
Oral poll, written poll, tests, check of results of laboratory work, discussion, discussion
The conclusion of the teacher on the yielded study. An evaluation of knowledge of students on 100 mark system and its announcement. A summer residence of the task for following employment (the complete set of questions)
Information, questions for independent work
10. Control questions.
Paths of formation of ammonia?
Specify sequence of the ferments, participating synthesis urea.
With what can be associated disturbance of synthesis urea?
Hyperammonemia, standard importance of urea in blood serum and urine?
What ferments participates in formation of biogenic amines?
Explain biological importance of biogenic amines?
Role of histaminum in development of allergic and inflammatory reactions?
Paths of disintegration of biogenic amines?
Where synthesis of urea and what ferments thus proceeds participate?
What methods it is possible to define urea level in blood serum and urine?
11. Recommended literature
1. N. V. Bhagavan «Medical biochemistry» fourth edition Corbis Corporation/William Whitehurst, 2001y.
2. T.T.Berezov, B.F.Korovkin «Biological chemistry» - Moscow 1990y.
3. R.A.Sobirova and others. Biological chemistry - Т, 2006
4. A.J.Nikolaev «Biological chemistry» - Tashkent, 1992y.
5. A.Lehninger «Principles of biochemistry» fifth edition by W. H. Freeman and Company 2008.
6. «Harper's Illustrated Biochemistry» 28e Robert K. Murray, David A Bender, Kathleen M. Botham, Peter J. Kennelly, Victor W. Rodwell, P. Anthony Weil
2. A.Wight and others «biological chemistry Bases» 1,2,3 volume, Moscow 1981y.
3. L.S.Strajer "Biochemistry" 1,2,3 volume, Moscow 1985y.
4. D.Mecler "Biochemistry" 1,2,3 volume, Moscow 1980y.
5. Z.Kru of "Biochemistry", Moscow 1979y.
6. E.A.Stroev «Biological chemistry» - Moscow 1986y.
7. A.Horst «Molecular bases of a pathogenesis» Moscow 1992y.