LESSON 1

Theme: Biochemistry of protein.

Aim of the lesson: To work out the skill of using the knowledge of physicochemical
properties of proteins in the practical work of a doctor.
Laboratory work:
1. To isolate proteins from biological material (hens egg, muscular tissue, blood).
2. To find the isoelectric point of different proteins.
Questions for self-control:
1. What is biochemistry? The position of biochemistry among other sciences, the aims of
biochemistry.
2. The basic stages in the history of biochemistry. The importance of biochemistry in the practical
work of a doctor.
3. Learn the methods of investigation which are used in medicine.
4. Estimate the importance of such physicochemical properties of protein as solubility and
precipitability.
Good morning! My name is.. I am your teacher of biological chemistry. You are going to
study biological chemistry during 2 semesters and after that you are going to take the exam.
Now Ill show you round the subdepartment. Follow me, please. Here is the assistants
room, you may always find me here. Here we have classrooms (119, 118, 120). Then
preparatory room this room is for the laboratory assistants. Then the room of the head of
subdepartment, professor Efremenko Vitaly Ivanovich. This is the classroom with the equipment
for laboratory works. And, at last, laboratory room. In this room laboratory assistants prepare
reagents for practical work. Lets go back to the classroom.
What is the plan of our work? At the beginning of the lesson you will have to answer (in
written form) the questions of the program control (initial control). The questions are based on the
theme of the lesson. There will be 10-15 minutes at your disposal for this kind of work. You should
bring thin notebooks; after completing this work you should hand in your notebooks. The mark for
your answer is registered. Ill take your notebooks with me and bring them back to the lesson.
The next kind of work is the discussion of the theoretical material. Then we will discuss the
methods used in laboratory works.

After the break, you will carry out laboratory work, make the protocol of the practical work,
make the conclusions after each work. At the end of the lesson, you should hand your notebooks
with protocols and Ill put my signature there. That will be the end of our lesson. You are to have
another notebook for protocols (48-96 sheets of paper). You may re-write questions to the lesson
and laboratory works from the books with operating instructions (Ill bring them to each lesson).
You will also have lectures on biological chemistry (1 lecture in 2 weeks). You should have
one more notebook for writing lectures.
The student-on-duty will be appointed for each lesson. What are the responsibilities of this
student? During the break, the student-on-duty should go to the laboratory room and take the tray
with reagents and all the necessary equipment for the laboratory work. At the end of the lesson
each student should clean his own place (wash the tubes and other equipment) and the studenton-duty gathers the equipment back onto the tray and takes the tray back to the laboratory room.
The student-on-duty should also erase the board.
Annotation of the theme: Biological chemistry is the science that studies the nature of
substances which are in the composition of live organisms, their transformations, and also the
connection of these transformations with the activity of organs and tissues in normal conditions of
vital activity and in disease.
The main aim of biological chemistry is the formation of systematic knowledge of
mechanisms and chemical composition of the basic substances of the organism and molecular
bases of biological processes which make the basis for the vital activity of the organism in health
and in disease.
Historically, there are 3 periods of the development of biochemistry. Static biochemistry
studies composition, structure and properties of excreted biological combinations.
The main aim of biochemistry is to fully understand the nature of chemical processes on
the molecular level which are connected with the activity of cells.
Dynamic biochemistry investigates the transformation of substances in the organism and
the importance of this transformation for the processes of vital activity.
The functional period is connected with the investigation of the connection between the
chemical processes and physiological functions.
There is double-sided connection between biochemistry and medicine. Due to biochemical
researches, the scientists managed to answer many questions dealing with the development of
2

disease. The investigation of the reasons and progress of some diseases led to the formation of
new fields of biochemistry.
We will learn several methods of investigation while studying this subject.
You will learn the following themes this semester: chemistry of simple and complex
proteins, vitamins, enzymes, hormones, biological oxidation. Themes for the next semester:
digestion, the exchange of carbohydrates, lipids, proteins, biochemistry of blood and kidneys.
After each theme you will have a test.
The main aim of our lessons is not only to have some knowledge but to use the knowledge
of biochemistry in you practical work. Good-bye! See you in a week.
Final test-control is based on the questions of test- and programme-control, solving of
situational problems, reports on the topic. After that, post-test is carried out.
Instructions for the students (on self-reliant work):
1) Learn the aims of practical lessons and self-reliant work;
2) Try to use the information from the previous lessons;
3) Learn the basic notions and concepts of the theme of the lesson;
4) Analyze the work, make calculations and make conclusions.

Lesson 2
Topic: Chemical structure of proteins.
Questions or self-training:
1.Proteins are the structural elements of all living organisms.
2.What does hydrolysis of the proteins mean? What are the condiditions of its carrying out? Kinds
of hydrolysis?
3.Protein structure.
Primary, secondary, tertiary, quaternary structure of proteins. Dependence of The biological
properties of proteins on the peculiarities of protein molecule structure.
4.Changing the protein content of the body: hereditary and derivered proteinopathies.
5.Classification of proteins. Simple and compound proteins.
Annotation to the lesson:
Proteins are molecular nitrogen containing compounds, build from the residues of amino
acids, connected with each other by the peptide bonds.
Every of million existing species of living organisms (bacteria, animals, men) Contains its
own unique set of proteins. All of them distinctly differ from proteins of the other organisms. All the
proteins consist of 20 amino acids that can be combined with each other in different sequences.
That s why form a great number of proteins.
Functions of proteins:
1. Catalic (fermentation) function. All the ferments are proteins (pepsin, trepsin, amylase, and so
on).
2. Transport function.
Hemoglobin carries oxygen from the lungs to the tissues and carbon doxide rom the tissues to
the lungs.
3. Feeding and reserve function. Egg albumin is a source of feeding for the fetus.
4. Receptor function. Proteins of the biogical membranes.
4

5. Contraction function.
Actin and myosin are proteins of the muscular tissue. Structural function/
Keratin of the hair, nails. Elastin of the vessels/
6. Defense function. -Anti-bodies of blood serum are formed in response to entry of foreign
substances into the organism.
7. Regulatory function.
Insulin, glucagon regulates the blood glucose level.
8. They support the physiological meanings of pH in the internal medium of the organism.
Proteins have 4 organization levels. Primary structure is a sequence of amino acids
polypeptide chain.
Any peptide is unique in its primary structure. It determines the subsequent levels of protein
molecule organization. Substitution of amino acids in a polypeptide chain or their loss leads to the
change of structure, properties and functions of peptides. For example: during mutation of the
coding the polypeptide chain of hemoglobin, glutamine in the 6-th position is substituted to valine.
Hemoglobin loses its ability to bind and transport oxygen. Erythrocytes take the shape of a sickle,
the disease is called a sickle-like cellular anaemia.
Secondary structure is a way of twisting, packing of polypeptide chain into -helix or any other
configuration. It arises spontaneously.
There are two types of it:
a) -helix
b) -structure
a) 1 turn of -helix contains 3,6 amino acid residues. There is a lot of cysteine in an -helix, it
forms disulfide bonds between the helix turns.
-structure.
This type is found in proteins of hair, museles, and nails. And other fibrille proteins. It contains
much alamine, glycine/
Hydrogen bonds stabilize the secondary structure.
Tertiary structure is a three demensionae form polypeptide helix 4 types of the intermolecular
bonds stabilize tis structure.
5

l. Covalent disulfide bonds between the residues of cysteine.

2-Non-covalent hydrogen bonds.
3.Electrostatic interactions between charged groups in side radicals.
4.Hydrophobic, van-der-vaals interactions.
According to the form of tertiary structure proteins are derived into lobular (ferments antibodes, hormones) and fibrille (hair Keratin.collogen).
Quaternary structure is a way of arranging in the space several polypeptide chains.
Here are some examples of proteins of guatenary structure: hemoglobin-4 subunits,
piruvatcarboxylase-72 subunits.
Proteins are classified into simple and complex ones. Simple proteins consist of
aminoacids only. They include: albumines globulins of blood plasm.
Albumins have little molecular mass they serve as transport. Proteinpathy is a change of the
protein structure of body tissue.
Congenitae proteinopathy is connected with the rimary damage in agenetic apparatus of the
body (sickle - like cellular anaemia).
Protein is not synthetized structure. With devired proteins the structure
is not damage, but changed, its distribution in tissue is different, or protein
function is disturbed.

Lesson 3
Topic: Chemistry of the nucleoproteins
Aim: To gain knowledge of the structure and biological role of nucleoproteins and to put it into
practice.
Questions for self-training:
1.What are nucleoproteins and what is there biological role?
2. Scheme of hydrolisis of nucleoproteins
3.Chemical structure of the nucleoproteins.
4. Chargaffs rules
5.Methods applied for the study of nucleoprotein structure.
Actuality of the topic:
To the most important scientific events of our century we should refer thst fact that genetic
information is coded by polymeric molecule of DNA, wich is formed only by 4 (four) types of
monomer units. It is the DNA that serves as a chemical base of heredity. Learning the structure
and functions of nucleic acids is necessary for understanding the main point of genetic processes
occurring in a cell. Its structure changing is the reason for hereditary diseases.
Nucleoproteins are compound proteins, that have their structure a protein part (that is simple
proteins - histones) and a prosthetic group, represented by nucleic acids DNA (deoxyribonucleic
asid) and RNA (ribonucleic asid).
Scheme of hydrolisis of nucleoproteins
Nucleoproteins
Protein

DNA, RNA

(histones)
polypeptides

aminoacids

polynucleotides

mononucleotides

nucleoside
purin bases

pentose

H3PO4
purins and pyrimidine bases

(ribose and deoxyribose)

Primary structure of nuclein acid is a sequence of nucleotides in a polynucleotide chain.
Nucleotides are bounds to each other by 3,5 phosphoesfer bounds.
In 1953 (nineteen-fifty-three) Wotson and Crieck calculated and proposed a model of
secondary structure DNA of a double helix. The double helix is formed by coupling of N-base of
another one. Between ofgenin and thymine 2 hydrogen bonds appear, and between guanine
and cytosine 3 hydrogen bonds. This accordance of bases is called complementarity.
Pentose phosphate frames are turned outside the helix. N bases face each other inside the
helix. One turn of a helix contains 10 nucleotides.
The chains are anti parallel.
American scientist Chargaff, Columbia University, established the following regularity of DNA
structure (chargaffs rules):
1) The sune of purine nucleotides equals the sune of pyrimidine nucleotides.
2) The number A equals the the number T.
The number G equals the the number C.
3) DNA of different tissues of the organism of the same species has the same nucleotide
content.
4) The DNA content of different species is different.
5) DNA nucleotide content does not change this aging and does not depend on environment.
Stability of a double DNA helix is kept up by:
1. Hydrogen bounds between the complementary pairs of -; -.
2. Hydrophobic forces between flat-lying N-based inside the helix column.
Secondary and tertiary RNA structure
Any RNA is a one-chain molecule. M.-RNA is a copy of a part of DNA molecule. The primary
structure of a certain protein is coded in it.
The secondary m. RNA is curved chain. The tertiary structure looks like a thread winded a
bobbin. The role of a bobbin plays a special protein (informer).
The secondary structure of RNA looks like a clover leaf. It is formed due to intra-chain coupling
of complementary nucleotides of separate portions of polynucleotide RNA chain.
8

CHEMICAL STRUCTURE OF PURINE AND

PYRIMIDIN NITROGEN BASES

Purine nitrogen bases

adenine

guanine
Pyrimidin nitrogen bases

cytosin

uracil

thimin

PENTOSE
CH2OH
O OH
H H
H
H
OH OH

ribose

CH2OH
O OH
H H
H
H
OH H

deoxyribose

OH
O P OH
OH
phosphoric acid

RNA
adenine
N- glycoside
bound

3,5 phosphoester
bound

cytosin

guanine

uracile

10

DNA

adenine
N- glycoside bound

3,5 phosphoester
bound

H
cytosin

H
guanine

uracile

11

Lesson 4
Topic: Protein Chemistry.
Questions for self-control:
1. Classification of conjugated proteins.
2. Chromoproteins; their chemical structure; myoglolin and Hb chemical structure. Abnormal
Hb. Glycosylated hemoglobin.
3. Glycoproteins. Chemical structure, biological role.
4. Phosphoproteins. Chemical structure, biological role.
Actuality of the topic:
A physician must know that almost all the proteins of human plasma, with the exception of
albumins as glycoproteins. Blood groups substances in some cases are glycoproteins; some
hormones (chorionic gonadotropin) have glycoprotein nature.
Recently, cancer is characterized more and more often as a result of abnormal gene regulation.
The main problem in a oncocological diseases is existing of metastasis, that is a phenomen,
which cancer cells leave the place of their origin and are carried by the blood flow to the distant
parts of the body, and grow unlimited with the catastrophic consequences for the patient. Many
oncologists consider metastasis to be conditioned by the change in structure of glycoconjugates
on the surface of cancer cells. Insufficient activity of various lysosome ferments destroying some
glycosaminglicanes is the basis of whole range of diseases (mucondysaecharidoses), as a result,
one or several of them accumulate in tissues and cause pathological symptoms. A physician must
also know that there are many forms of pathology connected, mainly, with hereditary disorders in
synthesis of apoprotein part of lipoproteins, as well as synthesis of key ferments or that of
lipoprotein receptors. They cause hypercholesterolemia and early atherosclerosis.
Training and educational aims
1. The total aim of the lesson: to work out the knowledge of structure and biological role of
conjugated proteins.
2. Particular aims: to form skills in carrying out analysis of conjugated proteins.
Annotation to the topic of the lesson
Conjugated proteins contain two components: protein and non-protein part that is called a
prosthetic group. In accordance with the character of this group one distinguishes:
12

Chromoproteins, nucleoproteins, metalproteins, Phosphoproteins, glycoproteins. Of great interest

is a subclass of Chromoproteins, to which hemoglobin, myoglobin, cytochromec, catalase are
refered.
Hb has a quaternary structure. Its molecular mass equals 66 000 68 000. Globin is a protein
part consisting of 4 subunits; and each of subunits is marked with
There are 2 chains, containing by 141 amino acid residues each and 2 -chains by 146
amino acids each. Their secondary structures are represented in a form of helix segments of
different length. Tertiary structure ofand -chains are similar. Inside any subunits
there is a hydrophobic pocket, where heme and hydrophobic amino acids radicals (these bonds
are about 60). Heme is a tetrapyrrol junction with atom Fe +2 , connected with pyrrol nitrogens, fifth
bound with imiidazol ring of histiding globin. The sixth coordinative bond Fe +2 is free and is used
for bounding of oxygen and other ligands.
Protein part of Hb molecule influences the properties of heme. Hb molecule interacts with
different ligands. Extremely high affinity of Hb to carbon oxide (II)-CO approximately 300 times is
high, that to oxygen (O2); it gives evidence of high toxicity of carbon monoxide. This form is called
carboxyhemoglobin, Fe+2 does not change it valence. Under the action of oxidizers (for example
sodium nitrate) mehtemoglobin appears; Fe is in oxidize stage +3 in it. The appearing of
hemoglobin in large quantities causes oxygen starvation of tissues.
One more derivative of Hb carbhemoglobin - may be formed when Hb is bound with CO 2;
however CO2 is connected not to the heme, but to NH2 hemoglobin groups (HbNH2 +
CO2HbNHCOO- + H+).
Carbaminoglobin production is used for leading out CO 2 from tissues to the lungs. By this way
10-15% of CO2 is taken out.
Hemoglobins may differ in to their protein path; according to this there physiological and
abnormal types of Hb.
Physiological Hb are formed at different stages of normal development of the organism, and
abnormal due to disturbance in hemoglobin. Hemoglobin physiological types differ from each
other for the set of polypeptide chains. There are distinguished Hb F (fetal hemoglobin) 1-2 %; Hb
A1 96%, Hb A2 2-3%, Hb A3 about 1% (hemoglobins of adults).
The Common group of diseases connected with Hb is called hemoglobinoses.

13

Among them we distinguish hemoglobinopathies; for example, sickle-like cellular anemia, when
substitution occurs in synthesis of -chains in the 6 th state (position) of glutaminic acid to
valine. Erythrocytes gain the form of a sickle, affinity to O 2 decreases. Thalassemia is a disease in
which synthesis of chain or -chain is completely destroyed (thats why it is called
-thalassemia or thalassemia).
It is known that the erythrocytes of diabetic patients contain some per cent of minor
component Hb, the so-called Glycosylated Hb.
To the pathogenesis of diabetic complication we may refer that fact that the amount of Hb Al C
A1C in patient increases (up to12-15%) in comparison of 4-6%. Glycosylated Hb (A 1C) represent -
(negative) charged minor components of Hb and differ from HbA by the presence of glucose
bound to valine at the aminoend of -chains. Reaction is reformed non=fermentatively and
depends on glucose concentration. So at insufficiently compensated diabetes total conjugation
HbA1C is above 12%.
Myoglobin has tertiary structure and represents one chain Hb (153 amino acids)
In contradistinction to Hb, it binds O2 5 times faster. Here is hidden the great biological sense,
as for as myoglobin is in the depth of muscular tissue (where is low partial pressure O 2).
Myoglobin produces an oxygen reserve which is used up in case of need, filling in the temporary
lack of O2.
Phosphoproteins represent proteins in which phosphate residuum is connected to hydroxyl
serine group with ester bond. Caseins, i. e (that is) milk proteins are referred to them.
Phosphoproteins are wide spread. Phosphorylation of protein changes its function. With the
help of special ferments phosphorylation and dephosphorilation of proteins (for example,
glycogenhosphorylase, lipase) regulates their function in a cell. Phosphorylation of histones
decreases their ability to form bpnds with DNA and to regulate DNA metrical activity.
Glycoproteins are proteins (carbohydrate content varies from 1 to85%), containing
oligosaccharide chains, connected covalently to polypeptide base. It is a numerous group of
proteins with different functions:
1) structural molecules
- cell wall
- collagen, elastin
- fibrins
14

- bone matrix
2) lubricating and defensive agents
- mucins
- mucose suretions
3) transport molecules for:
- vitamins
- lipids
- minerals and microelemets
4) immunological molecules
- immunoglobulins
- antigens of histocompatibility
- complement
- interferon
5) hormones
- chronic gonadotropin
- thyrotropin
6) ferments
- proteases
- nucleases
- glycosydases
- hydrolases
- clotting factor
7) sites of cell contacts/ recognition
- cell-cell
- virus-cell
- bacterium-cell
- hormone receptors

15

Lesson 5.
Topic: Chemistry of protein. (Control lesson).
Questions for self-training the students
1. What are proteins? What is their role in the organism?
2. Amino acids are components of proteins; their chemical structure.
3. Modern conceptions of protein molecule structure: primary, secondary, tertiary and quaternary
structures (methods of study, chemical bonds keeping these structures.
4. Classification of proteins.
5. Biological role, characteristics of simple proteins: albumins, globulins.
6. Biological role and structure of conjugated proteins: chromoproteins, glucoproteins,
phosphoproteins.
7. Nucleoproteins: biological role, chemical structure of nucleic acids.
8. Hemoproteins. Biological role, structure of heme.
9. Glycosylated

proteins.

Characteristics.

Glycosylated hemoglobin.

10.Determination of protein in biological material with the help of:

- Color reactions: biuret test, Folin's test.
-sedimentation reactions: with 10% TXY; concentrated HNCh; 5% Pb ()2;

16

Lesson 6.
Topic: Vitamins.
Aim: To form skills in use of the knowledge of vitamins, the action manifestation of their
deficiency the importance in practical activity of a doctor.
Questions for self training:
1. Concept of vitamin. Merits of scientists in development the study of vitamins.
2. Vitamins classification.
3. Presence of vitamins in nature; provitamins.
4. Hypovitaminosis, avitaminosis, hypervitaminosis, causes of origin.
5. Connection of vitamins and ferments. Mechanism of vitamin action.
6. Vitamins A, D, E, , Chemical structure, deficiency and biological role.
Vitamins are low molecular organic substances of varios chemical nature wich are
necessary for the nutrition of man and animals, but they do not perforue structural or energetic
functions.
The term vitamins was suggested in 1912 by Funk. (Vita- nuans life)
The principal point of vitamins classification, is based on their physical and chemical
properties:
1. fat- soluble vitamins: A, D, E, K;
2. water- soluble: B1, B2, B6, B12, H, PP, C;
The sources are:
- foods of vegetables and animals origin;
- microflora of intestine.
Some vitamins are produced by microflora of small intestine, for example, vitamins K, B 12,
chaline.
Provitamins are precursors of vitamins or non- active formsof vitamins.
It is known, the provitamins of vitamin A is , , carotene and under the action of intestinal
carotenase the are activized and turn into vitamin A.
Ergosterol and 7- dehudrocholesterol under ultra- violet light turns to vitamin D.
Hypovitaminosis is a pathological condition caused by insufficient consumption of vitamins,
certain clinical symptoms are not developed.
Symptoms: weakness, head-ache, rapid fatigue, decreassed resistance to infection.
17

Avitaminosis is a disease associated with absense of one or another vitamin in the body.
Avitaminoses result from hypovitaminoses and have a distinct clinical picture characteristic for an
individual avitaminosis.
Hypervitaminoses are diseases associated with exessive closes of vitamins taken for a
long period of time. They are often caused by fat- soluble that are able to accumulate in the
organism.
The causes of hypo- and avitaminoses can be divided into 2 groups.
1. Exogenous (alimentary form):
- insufficient content or lack of vitamins in food;
- disorder in a diet balance;
- one side nutrition;
- specific character of working activity;
- age and so on.
2. Endogenous (secondary avitaminoses):
- partial impairment in gastro-intestinal tract (low secretion of HCl);
- destruction of PP vitamin and other water- soluble vitamins;
- production disorder of internal Castles factor malignant anaemia;
- disorder in fat absorbtion; abstruction of bill ducts, impairment of pancreas function;
- changes of the genetic level-impairment of biosynthesis of protein wich is to bind vitamin
in cells (vitamin resistant condition).
Fat- soluble vitamins
Vitamin A- retino- axerophthol.
The main sources: milk, eggs, liver, red pulped fruit and vegetables.
Daily requirement-2,7 milligrams.
Retinol provides the growth, differentiation of tissues; retinol is important for normal function of
retina. Vitamin A takes part in proteins of glyciproteins and rhodopsin synthesis.
Avitaminosis of vitamin A causes night blindness (hemeralopia), infringement of sight
adaptation in the darkness. Delay of growth in young age, keratinization of the skin, caused by
delay in the exchange of epithelium, xerophthalmia, that is dryness of the mucous membrane of
an eye; the cornea becomes opaque and soft (keratomalacia), impairement of reproduction
function.
18

Vitamin D- calciferol- antirachitic.

The main sources: floods of animal and plant origin: liver, butter, milk, oils. The highest
amount of vitamin D presents in the fish liver oil.
Daily requirement: for adults- 2,5 milligrams a day. According to its chemical nature we may
refer it to sterins. The most active are: vitamin D2 ergocalciferol, vitamin D3 cholecalciferol.
Vitamin D2 is formed from the plant precursor (provitamin) ergosterol, vitamin D3 form 7dehydrocholesterin, wich is synthetized in the skin of man and animals under the effect of
ultraviolet rays.
Vitamin D is essential for the assimilation of calcium and for phosphorus- calcium metabolism.
- mobilization of calcium from bone tissues;
- reabsorbtion of calcium and phosphorus in renal tubules.
In general the action of vitamin D results in increase of iones Ca 2+ and phosphates in the
blood.
Avitaminosis gives its manifestations in rickets- that is disease characterized by a lack of the
last stage of bone formation- deposit of mineral substances on a bone matrix. It gives rise to
various skeletal deformities, such as: bow- legs; X- or Y- like legs; a pigeon- breast appearance of
the chest; the fontanel closes late.
Hypervitaminoses are accompanied by bone demineralization, fractures, and due to increased
concentration of calcium and phosphorus, by calcification of soft tissues and calcification in
kidneys.
Vitamin E- tocopherol- antisteril.
The main sources: vegetable oils.
Daily requirement: 10-20 mg a day.
Biochemical function: it is a biological antioxidant; it promotes stability of cell biological
membranes of the organism. It inhibits peroxide oxidation of polynon- saturated fatty acids,
increases the vitamin A activity; defencing its non-saturated side- chain from peroxide oxidation.
In experiments on animals hypovitaminosis manifestates itself in erythrocyte peroxide
hemolysis, testicle atrophy (male barrenness), muscular dystrophy, lives necrosis, softening of
some parts of the brain, especially cerebellum.
Vitamin K- naphtoquinone- antihaemorragic factor.
The main sources: liver, vegetables, fruits, beetroots, microflora of the intestine.
19

Daily requirement: 0,2 mg a day.

Biochemical function: it regulates the process of coagulation by taking part in formation of
clotting components: factor 2 (prothrombin), factor 7 (proconvertin), factor 9 (Christmass factor)
and factor 10 (Stewards factor) in the liver.
Deficiency: it is accompanied by profuse bleeding even at minor injury. Hypovitaminosis can
be caused by suppression of microflora with some medicines, liver diseases.
Water-soluble vitamins.
Vitamin C- ascorbic acid- antiscorbutic.
The main sources: fruit and vegetables (walnut, grapefruit, blackcurrants, dogrose, cabbage,
cranberry, pepper).
Daily requirement-50-100 milligrams.
The main function is in participation in oxidation- reduction reaction, and also in the following
conversions:
1. Hydroxylation of tryptophan in position 5 (serotonine synthesis).
2. Hydroxylation of DOFA (production of noradrenaline).
3. Hydroxylation of steroids (corticosteroids synthesis).
4. Hydroxylation of praline and lysine in procollagene (collagene synthesis).
5. Production of enzyme forms of folacine.
Besides, ascorbic acid takes part in iron metabolism: in the intestine it provides reduction of
trivalent iron into bivalent- it is compulsory condition for iron absorbtion; it releases iron from the
bound transport form in the blood (from the complex with transferrin), it provides its accelerated
penetration into the tissues.
Avitaminosis of vitamin C causes scurvy in man. Manifestation: spongy and bleeding gums,
teeth that loosen and fall out, hemorrhages in the muscles, skin and joints, increased porosity and
fragility of the bones, subcutaneous spot hemorrhages (petechiae), anorexia, anemia, low healing
of wounds, lassitude, head ache, dispnoe, heart- ache, edema, pain in the legs.
All these changes are caused by disturbance in collagen and chondroitinsulphat formation, by
increase of vessel penetration, decrease of blood coagulation. Anemia is conditioned by the
disturbance of coenzyme forms of folacine, decrease of DNA synthesis in hemogenic cells.
Odonto- and osteoblast synthesis is impaired.

20

Lesson 7.
Topic: Water-soluble vitamins.
Questions for self-control:
1. To study chemical structure, daily requirement, spreading, deficiency, biological role of
vitamins Bi5 B2, B6; Bi2, PP, H, P, folic, pantothenic acids.
2. Vitamins, anti-vitamins remedies.
We can abserve vitamins and ferments in active coenzyme forms and take part in
carbonhydrate, protein, lipid and mineral metabolism.
For example:
Vitamins

Coenzyme form

Type of catalyzed reaction

B1

thiamindiphosphate

decarboxylation of keto acids

B2

flavin adenin dinucleotide (FAD)

oxidation- reduction

flavin mononucleotide (FMN)

reactions

nicotinamide adenine dinucleotide

oxidation- reduction

(NAD)

reactions

PP

nicotinamide adenine dinucleotide

phosphate (NADP)
B6

pyridoxalphosphate

in reactions of

phosphopyridoxalaminophosphate

transamination and
decarboxylation of amino acids

biotin

transport of CO2 in
carboxylation reactions

Vitamin B1-thiamine- antineuritic.

21

It is active form thiamine diphosphate (TDF) is coenzyme of decarboxylases, which take part
in carbonhydrate metabolism.
Vitamin B1 is a cofactor of the following ferment systems:
1. Pyruvate-dehydrogenaze complex.
2. ketoglutarat dehydrogenase complex of fermento(Cycle of tricarbon acids-cycle of
Crabs) where molecules ATF are formed.
3. Transketolases of key ferment of pentose cycle; productions of this cycle are
necessary for fatty acids, acetylcholine, nucleic acids.
Thiamine is necessary for acetylcholine synthesis and for normal functioning of the
nervous system.
The most sensitive to the back of this vitamins are the organs with the mereased
carbonhydrate metabolism, that is nervous system and heart muscle.
Classical avitaminosis B1 is beri-beri , it is a rapea disease in Europe; but it often
occurs in those countries where poor population has insufficient nutrition and, their diet
consists of polished rice.
Subclinical forms with hyporeflexia and edema are registered in Japan.
Vitamin B2 (riboflavin) is an active part of the prosthetic group of flavin ferments. They
takes part in cell breath and vision pigment formation.
Physiological action of riboflavin is included in growth and body mass stimulation, in the
increase of diuresis and removal of salts with urine.
By its participation in tissue breathing vitamin B2 promotes normal functioning of
epithemical tissue, crystalline lens, and the tissue most sensitive to oxygen deficiency, for
example, the brain.
Deficiency manifestates itself mainly in tissues of endodermal origin eyes, skin. We
can observe conjunctivitis, edema, corneal epacification, glossitis and papilla atrophy.
Daily requirement of vitamins B2 is 2-4 mg.
Vitamin B6 - pyroxine antidermatic. This group consists of 3 substances mutually
transformed into each other in liver: pyridoxine, pyridoxal and pyridoxamine. Vitamins B6
comprises many ferments which take part in regulation protein and other kinds of
22

metabolism. It performs transportation of amino acids from the blood flow to the tissues;
it activates processes of transamination, desamination and decarboxylation of amino
acids. It stimulates synthesis of protein that transports iron in the blood, purine and
pyrimidines nucleotides.
Vitamin B12 - cyanocobalamine - is necessary for desoxyribose formation, as well as
DNA and nucleoproteins. It is necessary for normal growth, normal function of nervous
system, and normal blood formation.
At B12 deficiency erythroblasts cannot divide into megaloblasts, which produce large
immature forms of erythroblasts - megalocytes - specific for B 12 deficial anaemia.
Vitamin B12 is absorbed in the intestine only when it is connected with a specific
mucoprotein(Castles factor).There also the spinal cord - demyelination.
Daily requirement is 10-12 mkg.
Folic acid takes part in the transmission of methyle groups and is necessary for amino
acids exchange and synthesis of DNA. Tissues with rapid cell proliferation re especially
sensitive to the deficiency of folic acid (erythrocytes).
Daily requirement of folic acid is 1-2 mg.
Vitamin PP (nicotinic acid) is synthesized from tryptophane by intestine bacteria. Nicotinic
acid and its amid play an important role in organism, as nicotinamid is a coenzyme of
pyridine ferments (NAD and NADF), which take place in the oxidation - reduction
reactions.
Deficiency of vitamin PP gives rise to pellagra. The most characteristic features
of this disease are: a symptom of 3 Ds (dermatitis, diarrhea and dementia). Dermatitis
involve those exposed to the sun surface (back o the hand, neck, face). The skin
becomes red, then brown and rough.
Diarrhoea is accompanied with anorexia, nausea, vomiting, pain in the
abdomen. Specifies symptoms for pellagra are stomatites, gingivitis, tongue involvement.
Dementia - mental deterioration accompanied with head - ache, dizziness,
nervousness, depression.
23

Daily requirement of vitamin PP is 18 mg.

Vitamins used in medicine for the treatment of various diseases.
Forms of application: separate vitamins and complex vitamins.
During pathogenic treatment individual valuable properties of vitamins are used
(to dilate vessels, to regenerate and so on).
For example:
Vitamin A - regeneration of poor tissues, stimulation of growth end
development of children; prohlaxis of infertility; increase of resistance to in function.
Vitamin D is for rickets treatment, tuberculosis o bones an skin.
Vitamin B1 is used at diabetes mellitus to make better assimilation of
carbohydrates, at nervous diseases.
Vitamin C - at acute respiratory diseases, for stimulation of regeneration.

Lesson 8.
Topic: Vitamins, (control lesson).
24

Question for self-control:

1. Notion of vitamins and their use in medical practice. Merits of scientists in the development of
vitamins studies.
2. Classification of vitamins.
3. Hypo-, hyper- and avitaminoses, their causes.
4. Mechanism of water-soluble vitamins action.
5. Daily requirement of vitamins; factors, influencing the dayly requirement of vitamins.
6. What are pro-vitamins? Conditions, under which they are transformed into active
forms.
7. Anti-vitamins, their biological role, examples.
8. Vitamin A, daily requirement, chemical structure, deficiency, biological role.
9. Vitamin D, daily requirement, chemical structure, deficiency, biological role.
10. Vitamin E, daily requirement, chemical structure, deficiency, biological role.
11. Vitamin K, daily requirement, chemical structure, deficiency, biological role.
12. Vitamin PP, daily requirement, chemical structure, deficiency, biological role.
13. Vitamin C, daily requirement, chemical structure, deficiency, biological role.
14. Vitamin Bi daily requirement, chemical structure, deficiency, biological role.
15. Vitamin B2, daily requirement, chemical structure, deficiency, biological role.
16. Vitamin B6, daily requirement, chemical structure, deficiency, biological role.
17. Vitamin Bi2; daily requirement, chemical structure, deficiency, biological role.

Lesson 9
Topic: Enzymes.
25

Questions for self-control.

1. What are enzymes and what is their role in the body?
2. What is the importance of enzymes in diagnostics and disease prognosis
3. Nomenclature and classification of enzymes.
4. General properties of enzymes: specifity, temperature and pH-medium influence on enzymes
activity.
5. Chemical nature and mechanism of action of enzymes.
Annotation on the topic:
Ferments or enzymes (E) are specific proteins contained by all the body cells;
they are biological catalysts.
Enzymes are agents between the organism and the environment, promoting adaptation of the
organism to changing conditions (avtoregulators)
Various age transformations of enzyme induction are marked in ontogenesis. Different
induction periods determine the necessity for one or another enzyme to synthesize.
The most important factor, changing metabolism of a child organism, is the change of nutrition
conditions, the character of consumed food, in particular. It concerns not only hydrolytic enzymes
of gastro-intestinal tract. Activity of tissue enzymes depends on the quantity and quality of food.
For example, at ration, containing much protein in food there is observed an increased activity of
enzymes, synthetizing urea and amino acids transformation.
Certain enzyme content is characteristic for every tissue (organ) (marker enzymes). The marker
ferments of cardiac muscle are aspartataminotransferasa (AsT), and creatincinasa; of liver
alaninaminotransferasa (AIT); of prostate gland - acid phosphatase (APh); of pancreas a
amylase, etc.
In the diseases accompanied by necrosis the marker (organospecific) enzymes from damaged
cells enter blood flow in a great amount; their activity level increases, hyperfermentaemia
appears.
Determination of marker enzymes activity level in blood serum is of clinical importance in
diagnostics and prognosis of some diseases.
So, by myocardial infarction AcT activity level increases; by prostate gland cancer - that of
acid phosphatase; virus hepatitis - that of AIT; by pancreas disorders - of a - amylase, etc.
26

Some enzymes are used as medicines.

* Pepsin is used during the infringement of the synthesis and secretion pepsin in
stomach.
* Trypsin and chymotrypsin are used for the treatment of purulent wounds.
* Phybrinolyzin and streptochinasa are used for the preventing of thrombus formation during the
grafting of organs and other operations.
* Hyaluronidases provides for resolution of cicatrices.
* Asparaginasa is effective in treatment of some malignant neoplasms (cancer), etc.
By absence or lack of some enzymes, connected with mutation of a gene responsible for
protein-enzyme-ferment-synthesis, hereditary enzymopathies occur.
By phenylpyrovine oligophrenia hydroxylase ferment is absent; it catalyses phenylalanin
amino acid transformation into tyrosine.
It results into rise of phenylalanine level in blood and urine, and besides, phenylpyrovine acid is
produced from phenylalanine; it effects as a toxin upon central nervous system; as a result,
mental disability develops.
By galactosemia an enzyme ofgalactose-1-phosphate-uridyltransferase catalysing the
transformation of galactose-1-phosphate into glucose-1-phosphate is absent. This is the reason
for increasing of galactose and galactose-1- phosphate in blood; and this is accompanied by
vomiting, diarrhea, swelling of abdomen in infants.
Enzymes are classified according to the type of catalysed reaction. According to this
classification all enzymes are divided into 6 classes:
1. Oxydoreductases.
2. Transferases.
3. Hydrolases.
4. Isomerases.
5. Lyases.
6. Ligases.
Classes consist of subclasses, and subclasses consist of sub-subclasses. By chemical
nature all enzymes are proteins. They have physical and chemical properties of proteins:
high molecular mass, amphoterity, hydrophylia. They have electrophoretic mobility, high
specificity; they are liable to salting-out and denaturation.
27

In the organism any chemical reaction passes at definite energetic level, at definite
activation energy. Enzymes reduce activation energy by means of increasing the number of
activated molecules, which become reactive at lower energetic level.
Fermentation reaction is a multi-staged process. In the first stage approach and orientation
occur; and also induced complementary correspondance (ratio) between enzyme and substrate
becomes settled; as a result enzyme-substrate complex (ES) is formed.
In the second stage strain and deformation of substrate appears, it results in the shift of
electron density, change of polarization degree; bounds in substrate molecule are deformed and
are decomposed easily.
During the process of enzyme - substrate complex formation a transient state is achieved,
which is characterized by low activation energy, and as a result a new product is formed; and
after its dissociation the enzyme returns to its initial state.
Enzyme activity is effected by temperature, pH media, ion power of solutions.
As enzymes are proteins by chemical nature, temperature rise above 45-50C (Celsium
degrees) leads to heat denaturation; and enzymes become inactive (with the exception of
muscular myokinase, papain).
Low temperatures does not destroy enzymes, but only suspend their action. The optimum
temperature at which an enzyme shows maximum activity is 37 40 C.
Enzymes activity is effected by medium reaction. For every enzyme there is a pH where it
acts at its best and this is its optimal pH. The optimum pH of enzyme action ranges from 6,0 to
8,0 of its physiological meanings. Exceptions are: pepsin, pH optimum of which is 2,0; arginase pH optimum is 10,0.
Enzymes exhibit specificity. There are distinguished some types of specificity:
1. Absolute specificity - enzyme contacts with only one substrate. For example, urease
accelerates urea hydrolysis, but it does not breaks up thiourea.
2. Stereo-specificity enzyme contacts with a definite optical and geometrical isomer.
3. Absolute group specificity - enzymes are specific with regard to their bound character, and
also to those conjunctions that form this bound. For example, a -amilase breaks up a-glycoside
bound in a maltose molecule, consisting of 2 glucose molecules;
but it does not break up saccharose molecule, consisting of a glucose molecule and a fructose
molecule.
28

4. Relative group specificity. In this case enzymes are specific only with the regard to the
bound, but they are indifferent to those conjunctions, that form this bound. For example,
proteases accelerate peptide bounds hydrolysis in different proteins; Lipases accelerate the
break up of ester bounds in fats.

Lesson 10
Topic: Enzymes
Questions for self-control:

29

1. Structure of simple and complex enzymes (on the example of hydrolases, dehydrogenases).
2. Catalytic (active) and regulatory (allosteric) enzyme centers, (site)
3. Activators and inhibitors of enzymes, mechanism of their effect and importance.
4. Allosteric regulation of enzyme activity (regulation according to reaction of back-coupling
type).
5. Isoenzymes, immobilized enzymes , their significance in medicine.
Annotation to the lesson:
According to the composition all the enzymes are divided into simple and complex.
Simple enzymes consist of amino acids. Enzymes of gastro-intestinal tract are referred to
them.-that is a-amylase, pepsin, trypsin, lipase, etc. All these enzymes refer to the third class ~
hydrolases.
Complex enzymes consist of protein part (apoenzyme) and nonprotein part (cofactor). ^
Catalytic active complex "enzyme-cofactor is called holoenzyme. Both metallic ions and organic
compounds, many of which are vitamin derivatives, can be cofactors.
For example, oxidoreductases are used as cofactors Fe 2+, Cu2+, Mn2+, kinase Mg2+.
Coenzymes are organic substances unstable associated with a protein part. For example,
-dependants of dehydrogenase consist of protein and coenzymes of , ,
derivatives of vitamin PP.
Coenzymes being, bond firmly(often covalently) with apoenzyme, compose a prosthetic group.
For example, flavin dehydrogenases consist of protein and prosthetic groups , ,
derivatives of vitamin B2. Apoenzyme determines trend or specificity of enzyme action.
Active site is spatial organization of large complexes made of amino acid residues: serine OH group; cysteine - SH group; lysine NH2 group; histidine - imidazole ring; glutaminic, aspartic
acids - COOH group.
According to their primary structure these amino acid residues are arranged at different
distance from each other. During secondary and tertiary structure formation amino acid residues
are drawing together and form an active site.
The active site includes substrat-binding part (portion) which is responsible for specific
complementary binding of substrate; and catalytic part of direct chemical interaction.
30

Besides the active site, regulatory (allosteric) enzymes have allosteric site. Hormones or
reaction products can join allosteric site. It causes alteration of active site structure. These
substances are called allosteric effectors (modificators). Effectors can be positive (they increase
enzyme action) and negative (they block enzyme action).
Chemical reaction rate is influenced by different substances. According to their influence
character the substances are subdivided into activators (increasing enzyme activity) and
inhibitors (paralyzants) inhibiting enzyme activity.
Enzyme activation may be caused by:
1. Presence of cofactors-metallic ions Fe 2+, Mg2+, Mn2+, Cu2+, Zn2+, , lipoic acid.
2. Tneir partial proteolysis.
Gastro-intestinal tract enzymes are produced as inactive forms-zymogens. Under various
factors chipping off of peptide occurs with the formation of active site; and zymogen transforms
into active enzyme form.
Pepsinogen

HCL

Trypsinogen

enterokinase

pepsin + peptide
trypsin + peptide

This type of activation protects gastro-intestinal cells against selfdigestion.

3. Phosphorylation and dephosphorylation.
For example:
inactive lipase +-
lipase - phosphate + H3PO4

lipase - phosphate (active lipase)

lipasa (inactive lipase)

According to Ac type of action the inhibitors are divided into reversible and irreversible. Stability
of inhibitor and enzyme conjunction is die base of such division.
Reversible inhibitors are complexes which interact noncovalentiy with enzyme and can split off
the enzyme.
irreversible inhibitors are complexes with covalent, stable bonds with enzyme.
Irreversible inhibition may be specific and non-specific.
By specific inhibition, inhibitors reduce action of definite enzymes, binding some functional
groups of the active site. For example, thiol toxins inhibit enzymes; active site of them contains
SH-groups; carbon monoxide (CO) inhibits enzymes with Fe 2+ in their active site.
Non-specific inhibitors reduce effect of all enzymes. AH denaturating factors (high temperature,
organic and mineral acids, heavy metal salts, etc.) are referred to them.
31

Reversible inhibition can be competitive. Here inhibitor is a structural analogue to substrate

and competes with it for binding in a substrate-binding site of an active site.
A distinguishing feature of competitive inhibition is that it may be slacken or folly eliminated
after the increase of substrate concentration.
Succinic dehydrogenase (SDG) is a citrate cycle enzyme; it dehydrogenates succinate and
transforms it into fimarate. Malonate which is similar in structure with succinate is bound in an
SDG active site but it can not be dehydrogenated. That is why malonate is a competitive inhibitor
of SDG.
Many of medicines are competitive inhibitors of enzymes. For example, sulfanilamide
preparations being structural analogues of paraaminobenzoic acid (PABA),-that is the main
growth factor of morbific microorganisms, compete with it for binding in substrate-binding site of
enzyme active site.
Antimicrobial effect of sulfanilamide preparations is based on it.
Regulation according to back-coupling type (allosteric regulation of enzyme activity)
In some multi-stage metabolic processes the final product inhibits regulatory (allos-teric)
process enzyme.
At increased concentration of reaction Z product it is located in the allosteric site of regulatory
enzyme "E1. It is followed by alteration of active site "E1 conformation, and as a result, enzyme
"E1 is inhibited and can not combine with substrat "A". This regulation promotes organism
adaptation to changing environment. For example:
A

E1

E2

En

Isoenzymes are multiple forms of one and the same enzyme.

Isoenzymes catalyze the same reaction, but they differ in amino acid content and some
physical and chemical properties (molecular mass, electrophoresis mobility, etc.).
For example: lactate dehydrogenase (LDH) - (LDH) has five forms: LDH 12345
32

LDH catalyzes the reaction: Glucose

PVC lactic acid + 2 ATP

Every tissue has its definite isoenzyme spectrum of LDH: in a cardiac muscle there is
LDH 1,2 ; in a liver ~ LDH 4,5
Why is enzyme synthetized in several molecular forms?
In tissues with mainly aerobic metabolism (cardiac muscle), there prevail forms of
LDH 1,2 which provide tissues with a large amount of energy- 38 ATP molecules. In tissues with
anaerobic metabolism (liver, skeletal muscles) prevail LDH 4,5; and it results in formation of lactic
acid and 2ATP molecules.
To determine the isoenzyme activity level is of great importance in diagnostics.
For example, the increase of LDH 1,2 activity is observed in myocardial infarction; of
LDH 4, 5 ~ in hepatic diseases (hepatitis, cirrhosis).

Lesson 11
Topic: Enzymes.
Questions for self-control.

33

1. What are enzymes and what is their role in the body?

2.

What is the importance of enzymes in diagnostics and disease prognosis?

3.

Nomenclature and classification of enzymes.

4.

General properties of enzymes: specifity, temperature and pH-medium influence on

enzymes activity.
5.

Chemical nature and mechanism of action of enzymes.

6.

Structure of simple and complex enzymes (on the example of hydrolases,

dehydrogenases).
7.

Catalytic (active) and regulatory (allosteric) enzyme centers (site).

8.

Activators and inhibitors of enzymes, mechanism of their effect and importance.

9.

Allosteric regulation of enzyme activity (regulation according to reaction of back-

coupling type).
10. Isoenzymes, immobilized enzymes, their significance in medicine.

Lesson 12
Topic: Hormones.
Questions for self control.
1. Notion of hormones, their biological role. Classification.

34

2. The main mechanisms of metabolic regulation/ the role o central nervous system
(CNC) in metabolic processes regulation, releasing factors, liberins, statins, hormones of
hypophysis.
3. Cells, target organs, cell receptors of hormones. 3, 5 cAMP prostaglandins.
Mechanism of signal transmission to the cell (with the participation of protein-peptide
hormones, catecholamines, steroids and thyronines).
4. Mechanism of hormone action, mechanisms of immediate and chronic regulation.
5. Hormones produced by pancreas: insulin, glucagons; chemical structure,
mechanism of action; their influence to carbohydrates, fats and amino acids metabolism.
Transformation of metabolic processes in diabetes mellitus.
6. Hormones, and their influence on metabolic processes.
Actuality of the topic.
The physician must know what hormones are, what is their role in metabolic regulation; he
must know synthesis regulation and that of hormone secretion according to the back-coupling
mechanism, as well as target cells and cell receptors of hormones. He must understand the
mechanism of hormones signals to the cell, hormone status transformation and metabolism in
diabetes mellitus, pathogenesis of the main diabetic symptoms, as well as glucagons and
adrenalin influence the metabolic processes.
Annotation on the topic:
Hormones are biologically active substances synthetizing, as a rule, in the endocrine glands in
tracing quantities; when regulating metabolic processes they ensure stability of the body internal
medium.
Classification of hormones.
According to the site of synthesis all hormones are divided into actual and tissue ones.
Actual hormones are synthetized in the endocrine glands and are divided into three classes
according to their chemical structures:
1.

Hormones of protein-peptide nature-hormones of hypophysis and pancreas.

2.

Derivatives of tyrosine amino acids-medulla of adrenal gland hormones;

tyronines-hormones of thyroid glands.

3.

Steroids are hormones of adrenal cortex, sex hormones.

Tissue hormones are produced in tissues:

35

1.

Gastro-intestinal hormones-secretin and pancreozymin.

2.

Biogenic amines-histamine, serotonine.

3.

Prostaglandins.

4.

Kinins-bradykinin.

The leading role in regulation of all body function plays central nervous system (CNS).
Signals of internal and external body environment enter CNS. In the hypothalamus they
are transformed into releasing factors (RF). Releasing factors are peptides which contain from 3
to 14 amino acid residues. At present, there are liberated 7 liberins-releasing factors, which
stimulate hypophysis hormones synthesis; and 3 statins depressing hypophysis hormones
synthesis. For example, thyroliberin is a tripeptide which consists of glutaminic acid, histidine, and
praline. Thyroliberin stimulates production of thyrotropic hormone and prolactine in hypophysis.
Somato-statin is a peptide consisting of 14 amino acid residues; it inhibits somatotropic hormone
production in hypophysis.
Change of metabolites concentration in target cells according to the mechanism of
negative back-coupling inhibits hormone synthesis, effecting either endocrine glands or
hypothalamus; tropic hormones synthesis and secretion is inhibited by peripheral glands
hormones.
Produced hormones pass from the endocrine glands to the blood stream and then
accumulate in the certain target organs. Cells of the target organs contain cell receptorsglycoproteins in the quarternary structure. Cell receptors can place in a cell membrane,
cytoplasm and nucleus. Receptors have affinity to a hormone and from a complex with it without
energy consumption (spontaneously).
The number of receptors may very due to functional state of the organism; and in
pathological condition it may be a reason for some endocrine diseases.
Mechanisms of hormone signals transmission to cells.
1. Interaction of hormones of protein-peptide origin and catecholamines with a cell
(membrane mechanism).

36

Pancreatic hormones-glucagon, hormones of medulla of adrenal gland interact with cell

membrane receptors; and they form a certain complex. This complex activates the enzymeadenylat cyclase (AC) which is inside the membrane. Active adenylat cyclase catalyzes splitting
of ATP with 3 (prime) 5-cAMP formation (a secondary mediator), which activates the inactive
protein kinase, which, in its turn, activates inactive kinase; and the latter activates inactive
phosphorylase. Active phosphorylase splits glycogen and forms glycose wich is liberated into the
blood stream.
2.

Steroid hormones and tyronine interaction with a cell (cytozoic mechanism).

37

Hormones pass inside the cell and join the cytoplasmatic receptor, thus forming a complex.
This complex penetrates a nucleus and interacts with a nucleus receptor in chromatine; it
influences the transcription of u-RNA and, therefore, protein-enzyme synthesis.
Mechanism of hormone action:
1.

Hormones influence the penetrability of cell membranes;

2.

Hormones influence the enzyme activity, acting as allosteric effectors (mechanism

of immediate regulation)
3.

Hormones influence the enzyme synthesis (mechanism of chronic regulation).

Glucagon hormone, consisting of 29 amino acid residues, is secreted by pancreatic cells. It is made of a precursor-proglucagone, which in a process o partial proteolysis turns into
glucagon. Glucagon is produced in blood decreases (hypoglycaemia). Glucacon increases the
level of glucose in blood, owing to glycogene break up; it activates enzyme phosphorylase
according to immediate regulation mechanism (adenylat cyclase system).Besides, glucagon
stimulates glucose formation out of amino acids by mean of induction of glucogenesis enzymes
synthesis.
By -cells of pancreas insulin is produced from proinsulin precursor. Proinsulin, in its turn,
is produced of preproinsulin.
Insulin molecule consists of 2 polypeptide chains, connected with each other in two points
by disulfide bridges. A chain consists of 21 amino acid residues, B chain-of 30 amino acid
residues.
Insulin is produce when the level of glucose in blood is increasing (hyperglycaemia); at the
same time it decreases glucose content. Insulin increases the penetrability of cell membranes in
respect of glucose. Insulin is connected with SH-groups o cell membranes by disulfide bridges;
and as a result globular membrane is formed out of laminar one; and glucose passes inside the
cell.
Insulin activates enzyme hexokinase under allosteric interaction type; it catalyzes
transformation of glucose into glucose -6- phosphate.
Hexokinase
Glucose

glucose-6-phosphate

in the liver
glycogen
in tissue source of energy
38

Insulin, according to chronic regulation mechanism, is an inductor of enzyme hexorinase

synthesis and a repressor of gluconeogenesis enzymes synthesis.
At deficiency of insulin synthesis the insulin-dependent diabetes or the first type diabetes
occurs. The level of glucose in blood increases (hyperglycaemia); glucose appears in urine
(glucosuria), glycosylated haemoglobin content in blood is increased. Add this giver rise to the
following symptoms in diabetic patients: polyuria (frequent urination), as glucose increases
osmotic blood pressure; polydipsia (thirst, dryness in the mouth); polyphagia (frequent
consumption of food, hunger), as glucose is not oxidized and energy deficiency appears.
In the medulla o adrenal gland hormones are produced-adrenalin and noradrenalin. They
are synthetized from tyrosine amino acid.
Adrenalin and noradrenalin are referred to catecholamines, that is to the class of organic
substances with more strong biological action.
Adrenalin increases the level of glucose in blood due glycogen decomposition; it activates
phosphorylase enzyme according to immediate regulation mechanism (adenylat cyclase system).
Besides, adrenalin and noradrenalin are strong vasoconstrictors, causing the increase of arterial
pressure and the rate of heartbeats.

39

Lesson 13.
Topic: Metabolic regulation.
Questions for self-control.
1. Hormones of hypophysis, their chemical structure, effect to metabolism.
2. Adrenal cortex. Glycocorticoids, biosynthesis, their representatives, chemical structure, their
effect on the carbonhydrate metabolism. Mineral corticoids, structure, their effect on mineral salts
and water metabolism.
3.Hormones of thyroid gland, their structure. Clinical manifestation of hypothyroidism and
hyperthyroidism.
4. Endemis goiter. Reasons of pathology and preventive measures.
5. Hormones of parathyroid glad, their chemical structure, effect on metabolism.
6. Sex hormones, their chemical structure, effect on metabolism.
7. Use of hormones as medicine.
Annotation on the topic
1. There are 3 lobes in a hypophysis: the anterior lobe-adenohypophysis, the intermediate partglandular, and the posterior lobe or neurohypophysis.
The following hormones are produced in the anterior lobe of hypophysis: the somatotrophic
hormone (STH), adreno-corticotropic hormone (ACTH), thytroprophic hormone (TTH), the folliclestimulating hormone (FSH), the luteinizing hormone (ZH), prolactin.
Somatotropic hormone consists of 191 amino acid residues, it contains two disulfide bonds. STH
regulates the growth and development of the whole organism. Hypo function of STH-is
hepophysial dwarfism with proportional under-development of the whole body, including the
skeleton. Hyperfunction of STH in childhood results in gigantism with a proportional enlargement
of the skeleton. Hyper-unction of STH in the adults results in acromegaly-unproportionally
intensive enlargement of some body parts (hands, feet, lower, jaw, nose, tongue). Under the
effect of somatotropic hormone insulin and glucagone are produced in a pancreas. A small
concentration of TSH is observed in new born and infants under one year; it may be explained
by their intensive growth during this period of life.

40

Adrenocorticotropin hormone (ACTH) consist of 39 amino acids residues. It stimulates

synthesis and secretion of adrenal cortex hormones; it has fat-mobilizing and melanocyte
stimulating.
Thyrotropic hormone (TTH) consists of two and subunits; subunit contsins
96 amino acid residues; subunit contains 112 amino acid residues. In is a complex proteinglycoprotein. Under its influence hormones are produced in a thyroid gland.
Follicle-stimulating hormone and luteinizing hormone are compound proteins-glycoproteins. FSH
regulates the growth and maturation of follicles, as well as ovulation and transformation of the
follicle into the corpus luteum. In males ZH stimulates androgens secretion.
Prolactin stimulates mamma growth. Prolactin content in blood abruptly increases during the last
months of pregnancy.
Hormones of the posterior lobe of hypophysis are synthetized in special neurons in hypothalamus
then they transferred by neurons to the posterior lobe of hypophysis. One of them is vasopressin
which consists of 9 amino acid residues. It stimulates contraction of smooth muscles of vessels
and leads to a rising of blood pressure. Besides, it has an anti-diuretic effect-it stimulates
reabsorption of water through the renal canaliculus membranes.
At vasopressin deficiency a disease occurs-diabetes insipidus, a condition marked by an
enormous discharge of urine (10-20 litres a day) that contains no sugar.
Another hormone of the posterior lobe of the hypophysis-oxytocin-also consists of 9 amino acid
residues. In stimulates smooth muscles contraction.
Adrenal glands
The mutual precursor of all corticosteroid is cholesterol. During its synthesis more than40
metabolites are formed; and they differ in structure and biological activity. The main
corticosteroids with the marked hormonal activity are cortisol-glucocorticoid, aldosteronemineralo-corticoid and androgens. Stroid hormones are transported by blood together with the
special transport proteins. Synthesis and cortisol secretion rate is regulated by hypothalamic
hypophysal system according to feed back mechanism.
Glucocorticoids raise blood-sugar level; according to chronic regulation mechanism, they facilitate
synthesis of gluconeogenesis enzymes. Mineralocorticoid hold Na +, Cl+ ions and water in the body
(by increasing reabsorption) and promote the excretion of K + ions from the organism.
41

The catabolism of adrenal cortex hormones takes place in the liver first. Here the reactions of
hydroxylation, oxidation and reduction of hormones take place. Corticoid catabolism products
(except corticosteron and aldosteron) are excreted with urine in a form of 17-ketosteroids. These
metabolic products are excreted mainly in a from of conjugates with glucuronic and sulphuric
acids.
In males 2\3 (two thirds) of ketosteroids are formed from corticosteroids and 1\3-from
testosterones (only 12-17 mg a day).
Hypofunction of adrenal cortex hormones (hypocorticoidism), known as. Addisons disease or
bronzed disease, develops as a result of tuberculosis or autoimmune infringement. The clinical
manifestation are: hypoglycaemia, the excretion from the organism of great quantities of Na + and
Cl+ ions and water (diarrhea), dehydration, hypotention (low arterial pressure), holding of K + ions
in the organism. An intensive pigmentation of the skin is also observed. It is due to that fact that
according to feed back mechanism hypophysis produces much ACTH, which stimulates
production of skin pigment melanin.
Hyperfunction of adrenal cortex hormones (hypercorticoidism), known as Itsenko-Cushings
disease or steroid diabetes, is accompanied by hyperglycaemia, glucosuria; Great quantities of
Na+ and Cl+ions and water are held in the organism. It leads to edemas (moon-like face), and to
increasing of the arterial pressure.
Thyroid gland
The thyroid gland consist of glandular follicles (cavities) filled with a semi-fluid secretioncolloid. In these follicles iodinethyronines, composing thyroglobulin, are synthetized from
tyrosine amino acid and free iodine which enter the organism with food and water.
Under the effect of thyroperoxidase the oxidized iodine reacts with tyrosine residues; as a
result monoiodinethyronines (MIT) and diiodinethyronines (DIT) are formed. Two molecules of
DIT are condensing and produce thyroxin (T 4) , and MIT and DIT produce triiodinethyrinine (T3).
Iodinethyroglobin is transported to a cell by means of endocytosis and is hydrolysed by
lysosome enzymes with liberation of T3 (triiodinethyrinine) and T4 (tetraiodinethyrinine).
Synthesis of iodinethyronines is stimulated by TTH (thyrotropic hormone) of hypophysis.
Iodinethyronines regulate:
- growth, development and differentiation of tissue
42

- energy exchange
- carbonhydrate
- lipid metabolism
- hydro-electrolytic exchange and so on.
Hypofunction of thyroid gland in the early childhood leads to the development of a disease known
as cretinism (retarded growth, ugly disproportional body build, delayed mental development).
Hypofunction of the thyroid gland in the adults leads to the development of myxoedeme (edema
of the mucosa). Clinical manifestations are as follows: edemas (hydro-electrolytic exchange in
infringed), pathological obesity, falling out of hair and teeth. Basal metabolism is low.
Hyperfunction of the thyroid gland leads to the disease known as diffuse toxic goiter
(Basedows disease); it is accompanied by exophthalmos (protrusion of the eyeballs),
tachycardia, goiter (the enlarged thyroid gland); hightened basal metabolism. Body temperature
is high; the patients are extremely nervous; they have clammy hands; they are hungry.
It is due to that fact that thyroxin is a disconnected of oxidation and phosphorylation.
Endemic goiter is a disease, connected with the lack of iodine on food and water. It leads to
the compensatory enlargement of the mass of the thyroid gland due to the accretion of the
connective tissue.
One of the hormones of thyroid gland is calcitonin, consisting of 32 amino acid residues. It
regulated the exchange of phosphorus and calcium. Calcium decreases the content of calcium in
blood due to inhibition of its leaving the bone tissue and stimulated the excretion of calcium with
urine.
Parathyroid gland
Parathyroid gland, consisting of 84 amino acid residues is the antagonist of cacitonin as it
increases the level of calcium in blood due to the demineralization of bone tissue (washing-out of
calcium salts).
Besides, it increases the reabsorption of calcium in renal tubules and decreases the reabsorption
of phosphates. It leads to the reduction of phosphates in blood (hypophatemia), it promotes
enzyme activation phosphatase, which also washes out phosphoric and calcium salts from the
bone tissue. The synergist of parathyroid hormone is calcitroil, an active form of vitamin D 3, that
influences the synthesis of calcium binding protein in the intestine.

43

The sex glands. Female sex hormones.

They are synthetized from cholestered. Synthesis takes place in ovaries, adrenal cortex,
spermaries, placenta. Female sex hormones are divided into 2 groups that are different in
chemical structure and biological functions: oestrogens (estradiol) and progestins (progesterone).
The synthesis of female sex hormones is stimulated by the follicle-stimulating hormone and the
luteinizing hormone of hypophysis.
The synthesis of estrogens and progesterone starts with the beginning of puberty. They cause
the development of female secondary sex characters. Progesterone promotes successful
implantation of ovule in case of its fertilization into mucous membrane of the uterine. During the
pregnancy progesterone retards the ovulation and stimulates the development of mamma tissue.
Estrogens have anabolic functions and stimulate protein synthesis.
Male sex hormones.
Androgens are synthetized from cholesterol. Synthesis taken place in spermaries, adrenal cortex
and testicles. The main hormone is testosterone. In contradiction to estrogen, androgens already
in embrional period greatly influence the differentiation of male sex glands. In the adults
androgens regulate the development of male secondary sex characters and spermatogenesis.
Androgens have also considerable anabolic functions (they stimulate protein synthesis in all
tissues, especially in muscles).
Use of hormones for medical treatment
Hormones are used as replacement therapy in hypofunctions endocrine glands. For example,
insulin is used in diabetes mellitus of the first type, thyroxin in myxoedeme and so on.
Adrenaline, as a strong vasoconstrictor, is used in collapse, shock.
Female sex hormones are used in treatment of prostate gland cancer male sex hormones in
breast cancer.
Glucocorticoids are widely used in clinical practice. They have ante-inflammatory, anti-allergic
and anti-immune action; glucocorticoids are used for treatment of such diseases as: bronchial
asthma, rheumatoid arthritis, collagenoses (lupus erythematosus, scleroderma), various autoimmune diseases and so on. It is necessary to the feedback mechanism may lead to gland
atrophy.

44

Lesson 14.
Topic: Hormones (control lesson).
Questions for self - control.
1. Notion of hormones, the sites of hormones formation.
2. Classification of hormones.
3. The role of central nervous system in metabolic regulation. Mechanism of direct and "feed
back" connection.
4. Releasing- factors (liberins, statins), tropic hormones of hypophysis.
5. Cells, target- organs, cell receptors, hormones.
6. Interaction of hormones of protein and peptide nature, catecholamines, steroids and thyronines
with a cell.
7. Cyclic 3, 5'- AMP as mediator between hormones and intra-cellular mechanisms of hormone
activity realization.
8. Prostaglandins, their regulatory role.
9. Hormones of hypophysis, their influence on metabolism.
10. Hormones of the pancreas: insulin, glucagon; their chemical structure, mechanism of action;
influence of substances.
11. Hormones of medulla of adrenal gland: adrenalin, noradrenalin; chemical structure, their
influence on metabolic processes.
12. Adrenal cortex. Glycocorticoids; biosynthesis; representatives, chemical structure, influence
on metabolism. Mineral corticoids, structure, influence on mineral salts and water exchange.
13. Hormones of thyroid gland, structure. Influence on metabolism. Clinical manifestation
ofhypothyroidism and hyperthyroidism (cretinism, myxoedema, Basedow's disease).
14. Endemic goiter. Causes of pathology and ways of its prevention.
15. Hormones of parathyroid gland, their chemical structure, their influence on metabolism.
16. Sex hormones, their chemical structure, their influence on metabolism.
17. Use hormones as medicines.
18. By color reaction, prove that insulin is protein.
19. By means of color reaction, prove that there are amino acids, containing sulphur, in insulin.

45

Lesson 15.
Topic: Biological oxidation.
Question for self-control.
1. Concept of metabolism. Anabolic and catabolic processes and their interrelationship.
2. Exergonic and exergonic processes. Macroergonic compounds. ATP is a universal
accumulator and a universal source of energy in the organism.
3. Modern conceptions of biological oxidation and its role in the organism.
4. Place of oxidation. Substrates of oxidation.
5. Respiratory chain. Components of respiratory chain (complexes I, III, IV). Carriers of electrons
and protons along the chain.
6. Oxidazing phosphorulation. P/o coefficient. Free oxidation. Respiratory control.
Metabolism is a complex of anabolic and catabolic processes, taking place in the
human body.
Anabolic processes are the processes of synthesis of compound substances from simple
ones with energy expenditure.
Catabolic processes are the processes connected with break-down of compound
substances into more simple with energy emission.
Proteins, fats and carbohydrates are sources of energy in the body. This energy is concluded
in their chemical bonds produced as a result of transformation of sun energy during the
photosynthesis.
Products of break-down of proteins, fats and carbohydrates lead to energy production in a
form of ATP under oxidation. These processes, accompanied by energy emission, are called
exergonic processes.
For example: aerobic and anaerobic oxidation of glucose, oxidation of higher fatty acid.
The processes accompanied by energy absorption are called endergonic processes. ATP
takes the central place between this two processes. ATP is a macroergonic compound. The body
produces 62 kg of ATP daily.

46

ATP is a universal accumulator and source of energy, as only ATP energy is used for various
kinds of human body activity. For example, transmission of a nerve impulse, syntheses of various
substances, muscle construction, excretory function of kidneys, and so on.
Energy charge serves the index of energetic state of cells. It can be calculated using the
following formula:
[ATP] + [1/2 ADP]

= 0,9

[AMP] + [ADP] + [ATP]

AMP, ADP, ATP is called the adenylsystem of the body. If the whole adenylsystem is
represented only by ATP the cell charge is 1. If there is only AMP, then the cell charge equals 0
(zero). The living cell can maintain the level of energy charge.
So, lets see how proteins, fats and carbohydrates, as well as their break- down products
produce energy in a form of ATP.
If occurs by means of transformation of these organic substances from the moment of their
entering the human body up to production of ATP and final product of H 2O, CO2. These process
is called biological oxidation. It consists of 4 stages.
The first three stages are called stages of unification.
I. The first stage is splitting of nutrients to monomers in the gastrointestinal tract. Their
specificity is lost here. Proteins are splitted to amino acids, fats- to glycerin and higher
fatty acids, carbohydrates- to monosaccharides. During this stage 1% of energy is
released.
II. The second stage is intracellular catabolism by specific pathways (glucose oxidation,
higher fatty acids oxidation, and so on). This phase takes place in cytoplasm and goes on
up to acetyl CoA formation. As a result of this phase 20%-30% of energy is released.
III. The third stage is a general way of catabolism of tricarbonic acid cycle (Krebss cycle).
IV. The fourth stage is a terminal phase,- tissue respiration, when electrons and photons are
transmitted to O2 (oxygen) with ATP and H2O formation in the respiratory chain. At this
stage 70%-80% of energy is released.
Biological oxidation stages provide interrelationship of catabolic processes with tricarbonic
acid cycle and electrons transmission chain.

47

Organic substances oxidation in cells, accompanied by O 2 consumption during water synthesis, is

called a tissue respiration; and the electron transport chain is called a respiratory chain.
Electrons enter into the electron transport chain. In the course of their moving from one carrier
to another they lose their free energy. The significant part of this energy is storaged in a form of
ATP, and part of it is dispersed in a form of an ash.
1. The fourt stage, tissue respiration, takes its course with the following peculiarities:
1. at body temperatyre
2. at water presence
3. gradually, through numerous stages; thats why the energi is discharged by portions
and not like an explosion.
Respiratory chain organization.
There

can

be

lot

of

carriers

in

the

respiratory

chain.

(80

The main components of the respiratory chain are located in a strict order of oxidizing
reduction potential acceleration. Hydrogen nuclei or electrons move along the chain from the
more electronegative components to more electro- positive oxygen.

Thus, redox potential of

a hydrogen electrode is equal to- 0,42 and oxidizing- reduction potential of O2/H2O is +0,82.
Each carrier in a respiratory chain is in oxidated state at first; while receiving electrons it
transports

into

reduced

and

passes

electrons

to

the

next

carrier.

At the last stage the carrier gives back O2 electrons and reduces them to H2O.
The role of enzymes- carriers in the respiratory chain is reduced to activation energy
decreasing; free energy decreases and energy is released not in form of explosion but gradually,
in portions.

48

Components of respiratory chain.

Complex I -NADH dehydrogenase consists of several polypeptide chains. FMN plays the role of a
prosthetic group.
The only substrate of this enzyme is NAD. H, from which two electrons and a proton are
transported to FMN; producing FMN.H2. The second proton is absorbed from a matrix.
With FMNH2 electrons are transmitted then to the row of ferrum- sulphuric proteins (FeS), that
play the role of a second prosthetic group in the NAD.H- dehydrogenase complex I.
Ubiquinone (Q)
This is a non-protein carrier. Q structure is similar to vitamins K, E. Coenzyme Q content
significantly exceeds content of other components of respiratory chain.
1 mol. of NAD contains 50 molecules of CoQ. It allows to propose that CoQ is a mobile
component which gets an equivalents from fixed flavoproteins and passes them to cytochromes.
It is a collector of protons.
It can receive electrons from FAD succinatdehydrogenase this is complex II.
Cytochromes.
It is a group of compound enzymes; according their chemical structure they are
hemoproteins.
It contains heme as a prosthetic group. There are known 30 various cytochromes. Their variety is
caused by:
- difference of side chains in heme structure;
- difference in polypeptide chains structure;
- difference in the way of polypeptide chain connection (bond) with heme.
According to their ability to absorb light in a certain part of spectrum all cytochromes are
divided into groups a, b, c. Inside of every group, separate types owing the unique spectral
properties are marked with digital indexes- b, b1, b2 and so on.
49

5 types of cytochromes take part in electron transport chain: a1 a3 b c c1. ytochromes are
transported only by electrons.
Ferrum in a heme can change its valence.
(oxide form) ferrous oxide (protoxide form)
ytochromes are arranged in a certain order, redox potential order.
Complex III - Q H2 dehydrogenase.
It consist of 2 types of cytochromes b (b1 and b2) and cytochrome C1. This complex
transports electrons from hydroquinone to cytochrome C. Inside the complex electrons are
passed from cytochromes b to ferrum- sulphuric centers and then to cytochrome C1. And the
last cytochrome passed electrons to cytochrome C.
Cyt. C is a peripheral water- soluble membranous protein; it has one polypeptide chain
(consisting of 100 amino acid residues) and a heme covalently found with polypeptides.
Complex IV - cytochromeoxidase.
It consists of 2 cytochromes of a a3 type; each of them has a center (site) of oxygen binding.
Besides Fe, it contains Cu ions, bound with a protein part.
This complex reacts directly with molecular oxygen, it transfers electrons to it; and protons are
transferred from ubiquinone. It results in production of water and ATP energy.
Energy, released at electron transfer along the respiratory chain, is used for ATP synthesis. It
has 3 parts were electrons transfer is accompanied by relatively great decrease of free energy.
The amount of free energy that is necessary for ATP synthesis from ADP and phosphate, is
sufficient in these parts.
Complexes I, III and IV are the points of phosphorylation and respiration conjunction.
ATP synthesis from ADP and non- organic phosphate due to electron transfer along the
respiratory chain is called oxidizing phosphorylation.
Correlation of the amount of phosphoric acid used for ADP phosphorylation to the nucleus of
absorbed oxygen is called a oxidizing phosphorylation coefficient and is marked as P/O.
For the majority of substrates: NAD.H + H+ pyruvate, malate, isocitrate this coefficient equals
3.
On condition of FAD- dependent dehydrogenase action, complex II is omitted and thus, P/O=2.
We observe it in those cases when succinate, glycerol- 3 phosphate, and others are oxidation
substrates. Oxidation of adrenaline and ascorbic acid if performed under P/O equal 1.
50

By electron transfer along the chain, 40-45% of energy is used for ATP synthesis, 25% - for the
work on substance transfer through a membrane; the rest part of it is dispersed as heat and is
used for keeping up body temperature.
Additional heat production can occur at respiration and phosphorylation separation. It may be
useful for keeping up body temperature in newborns; they have special tissue- brown fat, which
produces heat by means of respiration and phosphorylation disconnecting. There is a special
disconnecting protein- thermogenine.
Disconnectors are lipophilic substances able to pass through the lipid layer of membrane:
- bilirubin
- thyroxine
- 2,4- dinitrophenol

51

Lesson 16.
Topic: Biological oxidation.
Question for self-control.
1. Crebss cycle (chemical reactions).
2. Energy balance of Crebss cycle.
3. The significance of Crebss cycle.
4. Hypoenergetic state
5. Free- radical oxidation, production of hydrogen peroxide, anion superoxide and their
further fate.
Crebss cycle was discovered by Crebs in 1937. (He was awarded the Nobel Prize in 1953).
That is why this cycle is called the Krebss cycle or citric acid cycle. Krebss cycle is a metabolic
process where proteins, fats and carbohydrates are consumed. All the reactions take their course
in a matrix of mitochondria.

52

53

54

The significance of Crebss cycle Integrational- it joints the pathways of protein, fat,
carbohydrate catabolism.
1. Plastic- tricarbonic acid cycle substrates are used for synthesis of other substances, for
example:
a). acetyl CoA is used for synthesis of cholesterol and its derivatives (bile acids,
provitamin D3, steroid hormone), higher fatty acids, acetylcholine.
b). CO2 is for synthesis of glucose, higher fatty acids, purine and pirimidine bases.
c). succinyl- CoA- for heme synthesis.
d). ketoglutarate- for glutaminic acid, proline, arginine.
e). oxaloacetate- for glucose synthesis, asparagine.
f). purovine acid- lysine synthesis, valine.
g). fumaric acid- for urea synthesis.
3. Energetic function. As a result of substrate phosphorilyzation one molecule of ATP is
produced.
4. Hydrogenerating- it supplies 4 pairs of hydrogen for the respiratory chain.
Infringement of Crebss cycle. (hypoenergetic state).
2. Krebss cycle substrates deficiency, for example:
In diabetes mellitus oxaloacetate concentration is reduced, at starvation.
3. Enzyme activity is changed when their synthesis is infringed and results in avitaminosis of
B, PP, B2, B3 and others.
4. Hypoxia, deficiency of O2 in the breathed in air: diseases of cardiovascular system,
respiratory system, anaemia.
Oxygen toxicity and hydrogen peroxide formation
(active form of oxygen).
Oxygen may be toxic.
Oxygen toxicity is conditioned by intermediate products under incomplete one- electron of
oxygen.
NO. nitrogen oxide
O2.- - superoxide anion
HO. hydroxyl radical
55

H2O2 hydrogen peroxide

They are active oxidizers; and turn them into new free radicals, giving rise to oxidizin chain
reaction. They are produced in the course of the following reactions:
Superoxide may be produced
1. by spontaneous hemoglobin oxidation.
Normally, Hb reversibly binds O2

Hb + O2 HbO2 oxihemoglobin.

However, oxihemoglobin turns into methemoglobin (contains Fe 3+, but not Fe2+) and
superoxide O2-. .
2. Grippe virus reacts with neutrophils of pulmonary tissue and prodused O 2.- , H2O2 which
maintains inflannation destructive changes.
3. Neutrophils, excessively accumulated in the inflamed joints, also produse O 2, promoting
the development of arthrites.
All these toxic radicals damage cells (they destroy proteins, lipids, membranes; they help
H2O, ions to penetrate a cell).
There exist some protective mechanisms:
1)

antioxidant enzymes superoxide dismutase, catalase peroxidase, glutathione

peroxidase.

2)

a trap for oxygen radicals vitamins C, E, glutathione, taurine (sulfhydryl

compounds), cysteine, bioflavonoids, uric acid.

56

Lesson 17.
Topic: Biological oxidation (control lesson).
1. Concept of metabolism. Anabolic and catabolic processes and their interrelationship.
2. Exergonic and exergonic processes. Macroergonic compounds. ATP is a universal
accumulator and a universal source of energy in the organism.
3. Modern conceptions of biological oxidation and its role in the organism. Stages of biological
oxidation.
4. Place of oxidation. Substrates of oxidation.
5. Respiratory chain. Components of respiratory chain (complexes I, III, IV). Carriers of electrons
and protons along the chain.
6. Oxidazing phosphorulation. P/o coefficient. Free oxidation.
7. Crebss cycle (chemical reactions).
8. Energy balance of Crebss cycle.
9. The significance of Crebss cycle.
10. Hypoenergetic state.
11. Free- radical oxidation, production of hydrogen peroxide, anion superoxide and their further
fate.

57