Amino acids are classified in several ways, depending on the feature by which they are divided into groups. There are basically three classifications of amino acids: structural - according to the structure of the side radical; electrochemical - for the acid-base properties of amino acids; biological (physiological) - according to the indispensability of amino acids for the body.

According to general formula a-amino acids differ only in the structure R, according to which they are divided into aliphatic (acyclic), cyclic (see diagram). Each group is divided into subgroups. So, amino acids of the aliphatic series, depending on the number of amino and carboxyl groups, are divided into monoaminomonocarboxylic, diaminomonocarboxylic, monoamine-carboxylic, diaminodicarboxylic. Some amino acids, already being part of proteins, can be modified, i.e. experience certain chemical transformations that lead to a change in the structure of the radical. They are not directly involved in protein synthesis. But they can be found in protein hydrolysates. So, as a result of the hydroxylation process that occurs in the body, OH groups are introduced into the side radicals of lysine and proline of collagen protein to form hydroxylysine and hydroxyproline.

This process takes place during the interaction of cysteine ​​residues in the polypeptide chain: both inside it and between polypeptide chains, it is observed during the formation of the spatial conformation of the protein molecule.

According to electrochemical (acid-base) properties, amino acids, depending on the amount of NH2 and COOH groups in the molecule, are divided into three groups: acidic - with additional carboxyl groups in the side radical (monoaminodicarboxylic acids: aspartic and glutamic) alkaline - diaminomonocarboxylic (lysine, arginine) and histidine; neutral - the rest of the amino acids in which the side radical does not show either acidic or alkaline properties. Some authors believe that in cysteine ​​and tyrosine, the sulfhydryl and hydroxyl groups in the side radical have slightly acidic properties.

The modern rational classification of amino acids is based on the polarity of the radicals, i.e. their ability to interact with water at physiological pH values ​​(about pH 7.0). It includes 4 classes of amino acids:

Non-polar (hydrophobic), the side radicals of which are not related to water. These include alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, proline;

Polar (hydrophilic) uncharged - glycine, serine, threonine, cysteine, tyrosine, asparagine, glutamine;

Polar negatively charged - aspartic and glutamic acids;

Polar positively charged - lysine, arginine, histidine.

According to the biological (physiological) value, amino acids are divided into three groups:

Irreplaceable, which cannot be synthesized in the body from other compounds, therefore, must necessarily come from food products. These are essential food supplements. There are eight essential amino acids for humans: threonine, methionine, valine, leucine, isoleucine, lysine, phenylalanine and tryptophan;

Napivzaminni amino acids can be formed in the body, but not in sufficient quantities, so they must partially come from food. For humans, such amino acids are arginine, tyrosine, histidine;

Essential amino acids are synthesized in the body in sufficient quantities from essential amino acids and other compounds. These include the rest of the amino acids. The above biological classification of amino acids is not universal, unlike the previous ones, and to a certain extent conditional, since it depends on the type of organism. However, the absolute indispensability of eight amino acids is universal for all kinds of organisms.

STRUCTURE, PROPERTIES AND CLASSIFICATION OF AMINO ACIDS AND PROTEINS

Amino acids are organic in structure. carboxylic acids, in which at least one hydrogen atom is replaced by an amino group. They are the building blocks of protein molecules, but the need to study them lies not only in this function.

Several of the amino acids are a source for the formation neurotransmitters in the central nervous system (histamine, serotonin, gamma-aminobutyric acid, dopamine, norepinephrine), others are themselves neurotransmitters (glycine, glutamic acid).

Certain groups of amino acids are necessary for the synthesis of purine and pyrimidine bases, without which there are no nucleic acids, they are used for the synthesis of low molecular biological important connections(creatine, carnitine, carnosine, anserine, etc.).

The amino acid tyrosine is a component of thyroid hormones and medulla adrenal glands.

A number of disorders are associated with amino acid metabolism. hereditary and acquired diseases accompanied by serious problems in the development of the organism (cystinosis, homocysteinemia, leucinosis, tyrosinemia, etc.). The most famous example is phenylketonuria.

CLASSIFICATION OF AMINO ACIDS

Due to the diverse structure and properties, the classification of amino acids can be different, depending on the quality of the amino acids chosen. Amino acids are divided:

1. depending on the position of the amino group.

2. According to the absolute configuration of the molecule.

3. According to optical activity.

4. The role of amino acids in protein synthesis.

5. According to the structure of the lateral radical.

6. By acid-base properties.

7. As needed for the body.

According to the absolute configuration of the molecule

According to the absolute configuration of the molecule, D- and L-forms are distinguished. The differences between the isomers are associated with the mutual arrangement of the four substituent groups located at the vertices of an imaginary tetrahedron, the center of which is the carbon atom inα-position.

The protein of any organism contains only one isomer, for mammals it is L-amino acids. However, optical isomers undergo spontaneous non-enzymatic racemization, i.e. L-shape becomes D-shape. This circumstance is used to determine the age, for example, bone tissue tooth (in criminology, archeology).

Depending on the position of the amino group

Allocate α, β, γ and other amino acids. For the mammalian organism, α-amino acids are the most characteristic.

By optical activity

By optical activity amino acids are divided into right- and left-handed.

The presence of an asymmetric carbon atom (chiral center) makes possible only two arrangements of chemical groups around it. This leads to a special difference between substances from each other, namely, a change in the direction of rotation of the polarization plane of polarized light passing through the solution. The angle of rotation is determined using a polarimeter. V

according to the angle of rotation, dextrorotatory (+) and levorotatory (–) isomers are isolated.

The division into L- and D-forms does not correspond to the division into dextrorotatory and levorotatory. For some amino acids, the L-forms (or D-forms) are dextrorotatory, for others they are levorotatory. For example, L-alanine is dextrorotatory, while L-phenylalanine is levorotatory. When mixing the L- and D-forms of the same amino acid, a racemic mixture is formed that does not have optical activity.

By the participation of amino acids in protein synthesis

There are proteinogenic (20 AA) and non-proteinogenic (about 40 AA). All proteinogenic amino acids are α-amino acids.

Using the example of proteinogenic amino acids, one can show additional ways classifications:

o according to the structure of the side radical- non-polar (aliphatic, aromatic) and polar (uncharged, negatively and positively charged),

o electrochemical- according to acid-base properties, neutral (most), acidic (Asp, Glu) and basic (Liz, Arg, Gis) amino acids are subdivided,

o physiological classification - if necessary, the body is isolated irreplaceable (Leu, Ile, Val, Fen, Tri, Tre, Liz, Met) and replaceable. Two amino acids are conditionally essential (Arg, His), i.e. their synthesis occurs in insufficient quantities.

I. Physico-chemical - based on differences in physical and chemical properties amino acids. one) Hydrophobic

amino acids (non-polar). The radical components usually contain hydrocarbon groups and

aromatic rings. Hydrophobic amino acids include ala, val, ley, ile, fen, tri, met. 2)

Hydrophilic (polar) uncharged amino acids. The radicals of such amino acids contain in their

composition of polar groups (-OH, -SH, -NH2). These groups interact with dipole molecules

waters that navigate around them. The polar uncharged include gly, ser, tre, tyr, cis, gln, asn.

3) Polar negatively charged amino acids. These include aspartic and glutamine

acids. In a neutral medium, asp and glu acquire a negative charge. 4) Polar positive

charged amino acids: arginine, lysine and histidine. They have an additional amino group (or

imidazole ring, like histidine) in the radical. In a neutral environment, lys, arg and gis acquire

positive charge.

II. biological classification. one)

Essential amino acids can not

synthesized in the human body

must necessarily come with food (val,

ile, ley, liz, met, tre, three, fen) and 2 more

amino acids are partially

irreplaceable (arg, gis). 2) Interchangeable

amino acids can be synthesized into

human body (glutamic acid,

glutamine, proline, alanine, aspartic

acid, asparagine, tyrosine, cysteine, serine and

glycine). The structure of amino acids. Everything

amino acids are α-amino acids.

Amino group of the common part of all amino acids

attached to the α-carbon atom.

Amino acids contain carboxyl

a -COOH group and an amino group -NH2. in protein

ionogenic groups of the common part of amino acids

participate in the formation of peptide bonds, and

all properties of a protein are determined only

properties of amino acid radicals.

Amino acids are amphoteric compounds.

isoelectric point amino acids are called the pH value, at

where the maximum proportion of amino acid molecules has a zero charge.

The main carbohydrates in food. Digestion of carbohydrates in the mouth and gastrointestinal tract,

amylolytic enzymes of saliva, pancreas, hydrolysis of disaccharides. Suction

monosaccharides (absorption mechanism).

By the number of carbohydrate residues, hydrocarbons are divided into 3 main classes: 1. monosaccharides (glucose, fructose, galactose, mannose, etc.); 2. disaccharides (maltose, sucrose, lactose); 3. Polysaccharides (homopolysaccharides starch, glycogen, fiber). Starch is a reserve homopolysaccharide of plants, built from α-glucose residues. Starch is a mixture of two homopolysaccharides: amylose and amylopectin. In amylose, glucose residues are linked by α-1,4-glycosidic bonds, at the branch points of amylopectin, by α-1,6-glycosidic bonds. The molecular weight of starch is 106-107. Glycogen is a reserve homopolysaccharide of higher animals and humans, built from α-D-glucose residues. Glycogen is found in almost all organs and tissues of humans and animals; Most of it is found in the liver and

muscles. The molecular weight of glycogen is 107 - 109 and above. Glycogen is similar in structure to amylopectin. Glucose residues are linked by α-1,4-glycosidic and α-1,6-glycosidic bonds (at branch points). The glycogen molecule has a greater number of α-1,6-glycosidic bonds compared to starch. Fiber is the only homopolysaccharide that is not digested in the human gastrointestinal tract. human digestive glands do not produce β-glucosidase. However, fiber performs a number of important functions: 1. promotes

the formation of feces; 2. enhances intestinal peristalsis; 3. is an adsorbent, with which excess cholesterol, salts of heavy metals are removed from the intestines. The role of carbohydrates: 1. Energy (glucose is the main source of energy for the body. When burning 1 g of hydrocarbons, 4 kcal of energy is released). 2. Structural-functional (HC is an essential component of glycoproteins and proteoglycans that perform various functions: hormonal, receptor, protective, enzymatic, etc.). 3. Metabolic (pentoses are involved in the synthesis of nucleic acids and nucleotide coenzymes). The daily requirement for carbohydrates is 400-500 g. Digestion of carbohydrates is a set of processes of phased enzymatic hydrolysis of polysaccharides to monosaccharides, which are absorbed in the intestine, carried by the bloodstream to the liver and other tissues of the body, where they undergo various metabolic transformations. HC digestion begins in the oral cavity under the action of the enzyme salivary amylase (optimum pH = 6.8-7.2), which hydrolyzes α-1,4-glycosidic bonds in starch to form dextrins .

HC suction from the intestinal lumen to the enterocyte and from the enterocyte to the blood occurs: 1) facilitated diffusion with the participation of carriers; 2) secondary active transport (symport with sodium ions) with

using the energy of K, Na-ATPase. Glucose and galactose are absorbed the fastest. From the intestines

absorbed monosaccharides are transported to the liver, where up to 90% of the conversion of monosaccharides occurs.

The entry of glucose into the cells of the heart, skeletal muscle and adipose tissue is regulated by insulin.

Quantitative determination of residual nitrogen in the blood.

The determination of residual nitrogen is carried out in protein-free blood filtrate. When heated with conc. the protein-free filtrate is mineralized with sulfuric acid and then determined colorimetrically with Nessler's reagent. Ammonium sulfate forms a yellow-orange color with Nessler's reagent. The calculation is carried out according to the amount of the standard solution of NH 4 Cl, which went to the titration of the experimental sample: (A 0.05) 100% = mg% 0.066 mg% = 0.714 = mmol/l, where A is the amount of standard solution used for titration.

20 – 40 mg% 15 – 25 mmol/l

An increase in the level of residual nitrogen (azotemia) is observed with a number of pathological conditions. In clinical practice, azotemia is divided into 2 types: retention and production. Retention mainly depends on insufficient kidney function and is due to a lack of urea. Production azotemia is associated with the entry into the bloodstream of an excess amount of nitrogen-containing substances, as a rule, due to increased breakdown of tissue proteins with preserved excretory function of the kidneys. The increased content of residual nitrogen (over 80 - 90 mg%) - uremia.

1. Molecular weight. Proteins are high molecular weight organic nitrogen-containing polymers,

built from amino acids. The molecular weight of proteins depends on the number of amino acids in each

subunit. 2. Buffer properties. Proteins are amphoteric polyelectrolytes, i.e. they combine sour and

basic properties. Depending on this, proteins can be acidic and basic. 3. Factors

protein stabilization in solution. HYDRATION SHELL is a layer of water molecules, in a certain way

oriented on the surface of the protein molecule. The surface of most protein molecules is charged

negative, and the dipoles of water molecules are attracted to it by their positively charged poles. 4.

Factors that reduce the solubility of proteins. The pH value at which the protein becomes

electrically neutral is called the isoelectric point (IEP) of the protein. For the main proteins, IET is in

alkaline environment, for sour - in an acidic environment. Denaturation is a consistent violation of the quaternary,

tertiary, secondary structures of the protein, accompanied by a loss of biological properties. Denatured

protein is precipitated. Protein can be precipitated by changing the pH of the medium (IEP), either by salting out, or by acting

any denaturation factor. Physical factors: 1. High temperatures. Some of the proteins undergo

denaturation already at 40-50 2. ultraviolet irradiation 3. X-ray and radioactive exposure 4.

Ultrasound 5. Mechanical impact (eg vibration). Chemical Factors: 1. Concentrated

acids and alkalis. 2. Salts of heavy metals (for example, CuSO4). 3. Organic solvents (ethyl

alcohol, acetone) 4. Neutral salts of alkali and alkaline earth metals (NaCl, (NH4) 2SO4)

2. Fats, or triglycerides - natural organic compounds, full esters of glycerol and

monobasic fatty acids; belong to the class of lipids. In living organisms perform structural,

energy and other functions. Along with carbohydrates and proteins, fats are one of the main components of nutrition.

liquid fats plant origin commonly referred to as oils.

hydrolysis of fats. The breakdown of fats into glycerol and fatty acids is carried out by processing them

alkali - (caustic soda), superheated steam, sometimes - mineral acids. This process

is called saponification.

Lipoprotein lipase- an enzyme belonging to the class of lipases. LPL breaks down the triglycerides of the most

large-sized and lipid-rich plasma lipoproteins - chylomicrons and lipoproteins

very low density (VLDL or VLDL)). LPL regulates the level of lipids in the blood, which determines its

importance in atherosclerosis.

Hyperlipidemia(hyperlipoproteinemia) - abnormally elevated

the level of lipids and/or lipoproteins in human blood. Violation of lipid and lipoprotein metabolism

quite common in the general population. Hyperlipidemia is an important risk factor

development cardiovascular diseases mainly due to the significant effect of cholesterol on

development of atherosclerosis. In addition, some hyperlipidemias affect the development acute pancreatitis.

Uric acid

The Muller-Seifert method is based on the ability uric acid react with a phosphorus-tungsten reagent to form a blue-colored compound. The intensity of staining is proportional to the amount of uric acid. According to the indications of FEC and according to the formula, the content of uric acid is calculated: Sst - Eop Mg% = Est, where Cst = 2 mg% Est = 0.06

2-6 mg% 0.12-0.36 mmol/l

Hyperuricemia is the main symptom of gout, and is also observed in Lesch-Nyhan syndrome, a congenital deficiency of the enzyme guanine-hypoxanthine phosphoribosyltransferase. The rise in uric acid may be the result of an increased breakdown of tissue nucleotides (a pathological change in the blood, myelosis). This phenomenon is called "secondary" gout. Some increase in uric acid is observed with a diet rich in purines. A decrease in uric acid is observed with acromegaly, Konovalov-Wilson disease, xanthinuria.

Structural organization of protein molecules. Primary, secondary, tertiary structures. Bonds involved in the stabilization of structures. Dependence of biological properties of proteins on secondary and tertiary structure. Quaternary structure of proteins. Dependence of the biological activity of proteins on the quaternary structure (change in the conformation of protomers).

There are four levels of protein spatial organization: primary, secondary, tertiary and quaternary structure of protein molecules. Primary structure of a protein- the sequence of amino acids in the polypeptide chain (PPC). The peptide bond is formed only by the alpha amino group and the alpha carboxyl group of amino acids. secondary structure- this is the spatial organization of the core of the polypeptide chain in the form of an α-helix or β-sheet structure. In the α-helix, there are 36 amino acid residues per 10 turns. The α-helix is ​​fixed with the help of hydrogen bonds between the NH-groups of one turn of the helix and the C=O groups of the adjacent turn. The β-sheet structure is also held by hydrogen bonds between the C=O and NH groups. Tertiary structure- a special mutual arrangement in space of helical and folded sections of the polypeptide chain. Strong disulfide bonds and all weak types of bonds (ionic, hydrogen, hydrophobic, van der Waals interactions) participate in the formation of the tertiary structure. Quaternary structure- three-dimensional organization in space of several polypeptide chains. Each chain is called a subunit (or protomer). Therefore, proteins with a quaternary structure are called oligomeric proteins.

Features of the chemical composition and metabolism nervous tissue(respiration, glucose and glycogen metabolism,

metabolism of macroergs, lipids, proteins and amino acids). Brain metabolism during hypoxia. Peptides and pain reactions.

Breath. The brain accounts for 2-3% of body weight. At the same time consumption

oxygen by the brain in a state of physical rest reaches 20–25% of the total consumption of it by all

organism, and in children under the age of 4 years, the brain consumes even 50% of the oxygen utilized by all

organism. V During the passage through the brain, the blood loses about 8 vol.% oxygen. In 1 min per 100 g brain

tissue accounts for 53-54 ml of blood. Consequently, 100 g of the brain consumes 3.7 ml of oxygen per minute, and

the whole brain (1500 g) - 55.5 ml of oxygen.

Metabolism of carbohydrates. The main substrate for the respiration of brain tissue is glucose. In 1 min 100 g

brain tissue consumes an average of 5 mg of glucose. It is estimated that more than 90% of the utilized glucose in tissue

the brain is oxidized to CO2 and H2O with the participation of the tricarboxylic acid cycle. Under physiological conditions, the role

pentose phosphate pathway of glucose oxidation in the brain tissue is small, however, this pathway of glucose oxidation

present in all brain cells. Formed during the pentose phosphate cycle, reduced

form of NADP (NADPH) is used for the synthesis of fatty acids and steroids. It is interesting to note that in

Based on the entire mass of the brain, the glucose content in it is about 750 mg. Per 1 min brain tissue

75 mg of glucose is oxidized. Therefore, the amount of glucose available in brain tissue could

be sufficient for only 10 minutes of a person's life.

Metabolism of macroergs. The intensity of renewal of energy-rich phosphorus compounds in the

brain is very large. This can explain that the content of ATP and creatine phosphate in the brain

tissue is characterized by significant constancy. If oxygen supply is cut off, the brain may

"exist" for a little more than a minute due to the reserve of labile phosphates.

Metabolism of amino acids and proteins The total content of amino acids in human brain tissue is 8 times

exceeds their concentration in the blood. The amino acid composition of the brain differs in a certain

specificity. Thus, the concentration of free glutamic acid in the brain is higher than in any other

mammalian organ (10 µmol/g). To the share of glutamic acid, together with its amide glutamine and

tripeptide glutathione accounts for more than 50% of α-amino nitrogen in the brain. It is known that the exchange

amino acids in the brain tissue flows in different directions. First of all, a pool of free amino acids

used as a source of "raw materials" for the synthesis of proteins and biologically active amines.

lipid metabolism Lipids make up about half of the dry weight of the brain. How

it was noted that in the nerve cells of the gray matter there are especially many phosphoglycerides, and in the myelin sheaths

nerve trunks- sphingomyelin. Of the phosphoglycerides in the gray matter of the brain, the most intense

phosphatidylcholines and especially phosphatidylinositol are updated. Myelin sheath lipid metabolism

flows at low speed. Cholesterol, cerebrosides and sphingomyelins are updated very slowly.

The brain tissue of an adult contains a lot of cholesterol (about 25 g). In newborns in

the brain only 2 g of cholesterol; its quantity increases sharply in the first year of life (about 3 times),

while the biosynthesis of cholesterol occurs in the brain tissue itself. In adults, the synthesis of cholesterol in

the brain is sharply reduced. The main part of cholesterol in the mature brain is in non-esterified

balanced state, cholesterol esters are found in a relatively high concentration in the precincts

active myelination.

The activity of aminotransferases (AlAt and AsAt) in the blood.

The method for determining the activity of AlAt and AsAt is based on the determination of the optical density of diphenylhydrazone pyruvate, which is the product of deamination of alanine and aspartate.

AlAt 0.1-0.7 AsAt 0.1-0.55

Increased activity of aminotransferases in blood serum noted in a number of diseases, and especially in lesions of organs and tissues rich in these enzymes (liver, myocardium). AsAt - a sharp increase 6-12 hours after the onset of myocardial infarction, reaches a maximum by 24-48 hours, and then gradually returns to normal by day 5. If by 4-5 days the activity of AsAt does not decrease, then the prognosis is poor. AlAt - for liver diseases, toxic liver damage, cholepathies, cholestasis, dermatomyositis. An increase in ALT activity is observed with acute infarction myocardium, but not so sharply compared with the change in ASAT. Normally, the ratio of the activity of AlAt and AsAt = 1.33±0.42. In patients with infectious hepatitis, the coefficient decreases, and in myocardial infarction, it increases sharply.

The structure of enzymes. Structure and functions of the active center. The mechanism of action of enzymes. Cofactors

enzymes: metal ions and coenzymes, their participation in the work of enzymes. Enzyme activators: mechanism

actions. Inhibitors of enzymatic reactions: competitive, non-competitive, irreversible. Medicinal

drugs - enzyme inhibitors (examples).

By structure, enzymes can be:

1. one-component (simple proteins),

2. two-component (complex proteins).

For enzymes - simple proteins- include digestive enzymes (pepsin, trypsin). For enzymes -

complex proteins - include enzymes that catalyze redox reactions. For

catalytic activity of two-component enzymes requires an additional chemical component,

which is called cofactor, they can be played as inorganic substances ( ions of iron, magnesium, zinc,

copper, etc..), and organic substances - coenzymes (for example, active forms of vitamins). For work

a number of enzymes require both coenzyme and metal ions (cofactor). Coenzymes - low molecular weight

organic substances of non-protein nature, associated with the protein part of the enzyme temporarily and unstable. V

case when the non-protein part of the enzyme (coenzyme) is firmly and permanently bound to the protein part, then such

the non-protein part is called prosthetic group. The protein part of a complex protein-enzyme is called

apoenzyme. Together, the apoenzyme and cofactor form holoenzyme.

In the process of enzymatic catalysis, not the entire protein molecule takes part, but only

a certain site is the active site of the enzyme. active center enzymes represent part of a molecule

enzyme, to which the substrate is attached and on which the catalytic properties of the molecule depend

enzyme. V active center enzyme secrete "contact" section- area that attracts and

retaining the substrate on the enzyme due to its functional groups and "catalytic"

plot, the functional groups of which are directly involved in the catalytic reaction. At

some enzymes, in addition to the active center, there is another "other" center - allosteric. WITH

allosteric various substances (effectors) interact at the center, most often various

metabolites. The connection of these substances with the allosteric center leads to a change in conformation

enzyme (tertiary and quaternary structure). An active site in an enzyme molecule is either created or it

is violated. In the first case, the reaction is accelerated, in the second case, it is inhibited. Therefore, the allosteric center

called the regulatory center of the enzyme. Enzymes that have an allosteric center in their structure

are called regulatory allosteric.Based on the theory mechanism of action of enzymes supposed

formation of an enzyme-substrate complex. The mechanism of action of the enzyme:

1. formation of an enzyme-substrate complex, the substrate is attached to the active center

enzyme.

2. at the second stage of the enzymatic process, which proceeds slowly,

electronic rearrangements in the enzyme-substrate complex. Enzyme (En) and substrate (S) start

approach to make maximum contact and form a single enzyme-substrate

complex. The duration of the second stage depends on the activation energy of the substrate or

energy barrier of this chemical reaction. Activation energy is the energy required for

transfer of all molecules of 1 mol S to the activated state at a given temperature. For each

A chemical reaction has its own energy barrier. Through the formation of an enzyme

substrate complex, the activation energy of the substrate decreases, the reaction begins to proceed for more

low energy level. Therefore, the second stage of the process limits the rate of the entire catalysis.

3. at the third stage, the chemical reaction itself occurs with the formation of reaction products.

The third stage of the process is short. As a result of the reaction, the substrate is converted into a product

reactions; the enzyme-substrate complex breaks down and the enzyme comes out unchanged from

enzymatic reaction. Thus, the enzyme makes it possible, through the formation of enzyme-

substrate complex to undergo a chemical reaction in a roundabout way at a lower

energy level.

Cofactor- a non-protein substance that must be present in the body in

small amounts so that the corresponding enzymes can perform their functions. Part

cofactor includes coenzymes and metal ions (for example, sodium and potassium ions).

All enzymes are globular proteins, and each enzyme performs a specific function,

associated with its inherent globular structure. However, the activity of many enzymes depends on

non-protein compounds called cofactors. Molecular complex of the protein part (apoenzyme) and

cofactor is called a holoenzyme. The role of a cofactor can be performed by metal ions (Zn2+, Mg2+, Mn2+, Fe2+,

Cu2+, K+, Na+) or complex organic compounds. Organic cofactors are commonly referred to as

coenzymes, some of them are derivatives of vitamins. The type of relationship between an enzyme and

coenzyme can be different. Sometimes they exist separately and communicate with each other during

the course of the reaction. In other cases, the cofactor and enzyme are linked permanently and sometimes strongly.

covalent bonds. In the latter case, the non-protein part of the enzyme is called the prosthetic group.

The role of the cofactor basically boils down to the following:

Changing the tertiary structure of the protein and creating complementarity between the enzyme and the substrate;

Direct participation in the reaction as another substrate.

Activators may be:

1) cofactors, because they are important participants in the enzymatic process. For example, metals included

into the catalytic center of the enzyme: salivary amylase is active in the presence of Ca ions,

lactate dehydrogenase (LDH) - Zn, arginase - Mn, peptidase - Mg and coenzymes: vitamin C, derivatives

various vitamins (NAD, NADP, FMN, FAD, KoASH, etc.). They provide active binding

center of the enzyme with the substrate.

2) anions can also have an activating effect on the activity of the enzyme, for example, anions

Cl- activate salivary amylase;

3) activators can also serve as substances that create the optimal pH value of the medium for development

enzymatic activity, for example, HCl to create an optimal environment for gastric contents for

activation of pepsinogen to pepsin;

4) activators are also substances that convert proenzymes into an active enzyme, for example,

intestinal juice enterokinase activates the conversion of trypsinogen to trypsin;

5) activators can be a variety of metabolites that bind to the allosteric center

enzyme and contribute to the formation of the active site of the enzyme.

Inhibitors are substances that inhibit the activity of enzymes. There are two main types

inhibition: irreversible and reversible. With irreversible inhibition - the inhibitor is firmly (irreversibly)

binds to the active site of the enzyme by covalent bonds, changes the conformation of the enzyme. So

Thus, salts of heavy metals (mercury, lead, cadmium, etc.) can act on enzymes. reversible

inhibition is a type of inhibition where enzyme activity can be restored.

Reversible inhibition is of 2 types: competitive and non-competitive. With competitive

In inhibition, usually the substrate and the inhibitor are very similar in chemical structure. With this form

inhibition, the substrate (S) and the inhibitor (I) can equally bind to the active center of the enzyme. They

compete with each other for a place in the active center

enzyme. Classic example, competitive

inhibition - inhibition of action

succinate dehydrogenase malonic acid.

Non-competitive inhibitors bind to

allosteric center of the enzyme. Therefore

changes in the conformation of the allosteric

center, which lead to deformation

catalytic center of the enzyme and reduce

enzymatic activity. Often allosteric

metabolic products are non-competitive inhibitors. medicinal properties inhibitors

enzymes (Kontrykal, Trasilol, Aminocaproic acid, Pamba). Kontrykal (aprotinin) is used for

treatment of acute pancreatitis and exacerbation chronic pancreatitis, acute pancreatic necrosis, acute

bleeding.

The concept of blood proteins. Blood proteins as a heterogeneous system. Separate functions of proteins, their

functional role. Physiological and pathological proteins. Qualitative and quantitative changes

blood proteins. The concept of hyper-, hypo-, paraproteinemia. Protein ratio.

Of the 9–10% dry residue of blood plasma, proteins account for 6.5–8.5%. Using method

salting out with neutral salts, blood plasma proteins can be divided into three groups: albumins,

globulins and fibrinogen. The normal content of albumin in blood plasma is 40–50 g/l, globulins

– 20–30 g/l, fibrinogen – 2.4 g/l. Blood plasma devoid of fibrinogen is called serum. Synthesis

plasma proteins is carried out mainly in the cells of the liver and reticuloendothelial system.

Physiological role blood plasma proteins is multifaceted. 1. Proteins support colloid osmosis

(oncotic) pressure and thus a constant blood volume. Plasma protein content is much higher

than in tissue fluid. Proteins, being colloids, bind water and retain it, preventing it from leaving.

from the bloodstream. Although oncotic pressure is only a small part (about 0.5%)

from the total osmotic pressure, it is it that determines the predominance of the osmotic pressure of the blood over

osmotic pressure tissue fluid. 2. Plasma proteins are actively involved in coagulation

blood. A number of proteins, including fibrinogen, are major components of the blood coagulation system. 3.

Plasma proteins to a certain extent determine the viscosity of the blood, which, as noted, is 4 times higher than the viscosity

water and plays an important role in maintaining hemodynamic relationships in the circulatory system.

Quantitative determination of vitamin C in urine.

The amount of ascorbic acid is determined titrimetrically by the amount of 2,6-dichlorophenolindo-phenol used for titration, and is calculated for the daily amount of urine. 2,6-dichlorophenolindophenol ( of blue color) is restored and discolored by vitamin C.

20 - 30 mg of ascorbic acid per day

Urinary excretion of vitamin C is reduced in scurvy, acute and chronic infectious diseases, with insufficient intake of vit. With food. DIAGNOSIS OF HYPOVITAMINOSIS C: when 100 mg of ascorbic acid is introduced into the body in a healthy person, the concentration of vitamin C in the urine increases. With hypovitaminosis, tissues are delayed ascorbic acid and its excretion from the body is reduced.

glycoproteins can be represented by monosaccharides (glucose, galactose, mannose, fructose, 6-

deoxygalactose), their amines and acetylated derivatives of amino sugars (acetylglucose,

acetylgalactose. The share of carbohydrates in glycoprotein molecules is up to 35%. Glycoproteins

predominantly globular proteins. The carbohydrate component of proteoglycans can be represented

several chains of heteropolysaccharides. biological functions glycoproteins: 1. transport(proteins

blood globulins transport ions of iron, copper, steroid hormones); 2. protective: fibrinogen

carries out blood clotting; b. immunoglobulins provide immune defense; 3. receptor(on the

receptors are located on the surface of the cell membrane, which provide specific

interaction).4. enzymatic(cholinesterase, ribonuclease); 5. hormonal(anterior lobe hormones

pituitary - gonadotropin, thyrotropin). Biological functions of proteoglycans: hyaluronic and

chondroitin sulfuric acid, keratin sulfate perform structural, binding, surface-mechanical

Enzymes that are normally found in plasma or serum conditionally can be divided

into 3 groups: secretory, indicator and excretory.

secretory enzymes, being synthesized in the liver, they are normally released into the blood plasma, where they play

certain physiological role. Typical representatives of this group are enzymes,

involved in the process of blood coagulation, and serum cholinesterase.

Indicator (cellular) enzymes enter the blood from the tissues, where they perform certain

intracellular functions. One of them is located mainly in the cytosol of the cell (LDH, aldolase), others

- in mitochondria (glutamate dehydrogenase), others - in lysosomes (β-glucuronidase, acid phosphatase), etc.

Most of the indicator enzymes in the blood serum are normally determined only in trace amounts.

When certain tissues are damaged, enzymes from the cells are "washed out" into the blood; their activity in serum

increases sharply, being an indicator of the degree and depth of damage to these tissues.

excretory enzymes synthesized mainly in the liver (leucine aminopeptidase,

alkaline phosphatase, etc.). In physiological

conditions, these enzymes are mainly excreted in the bile. The mechanisms have not yet been fully elucidated

regulating the flow of these enzymes into the bile capillaries. With many pathological processes

the excretion of excretory enzymes with bile is impaired, and the activity in the blood plasma increases.

Most of the enzymes contained in the liver are also present in other tissue organs. However, known

enzymes that are more or less specific to liver tissue. For such enzymes, in particular,

refers to γ-glutamyltranspeptidase, or γ-glutamyltransferase (GGT). This enzyme is

highly sensitive indicator in liver diseases. An increase in GGT activity is noted in acute

infectious or toxic hepatitis, liver cirrhosis, intrahepatic or extrahepatic obstruction

biliary tract, primary or metastatic tumor lesions of the liver, alcoholic lesions

liver. Sometimes an increase in GGT activity is observed with congestive heart failure, rarely -

after myocardial infarction, with pancreatitis, pancreatic tumors.

Organ-specific enzymes for the liver, histidase, sorbitol dehydrogenase, arginase are also considered

and ornithinecarbamoyltransferase. Changes in the activity of these enzymes in the blood serum indicate

damage to the liver tissue. Currently, a particularly important laboratory test has become a study

activity of isoenzymes in blood serum, in particular LDH isoenzymes. It is known that in the heart muscle

The isoenzymes LDH1 and LDH2 have the highest activity, and in the liver tissue - LDH4 and LDH5.

Polar (hydrophilic) amino acids

negatively charged amino acids

Some proteins contain specific amino acid derivatives. In collagen (protein connective tissue) hydroxyproline and oxylysin were found. The basis of the structure of hormones thyroid gland is diiodotyrosine, a derivative of tyrosine.

A common property of amino acids is amphotericity(from the Greek amphoteros - bilateral). In the pH range of 4.0-9.0, almost all amino acids exist in the form of bipolar ions (zwitterions). Meaning amino acid isoelectric point (IEP, pI) calculated by the formula:

.

pI for monoaminodicarboxylic acids is calculated as half the sum of pK values ​​(Table 1) of a- and w-carboxyl groups, for diaminomonocarboxylic acids - as half the sum of pK values ​​of a- and w-amino groups.

There are non-essential amino acids that can be synthesized in the human body, and essential ones that are not formed in the body and must be supplied as part of food.

Essential amino acids: valine, threonine, leucine, lysine, methionine, tryptophan, isoleucine, phenylalanine.

Non-essential amino acids: glycine, alanine, aspartate, asparagine, glutamate, glutamine, serine, proline.

Conditionally Essential Amino Acids(can be synthesized in the body from other amino acids): arginine (from citrulline), cysteine ​​(from serine), tyrosine (from phenylalanine), histidine (with the participation of glutamine).

The relative content of various amino acids in proteins is not the same.

For the detection of amino acids in biological objects and their quantitative determination, a reaction with ninhydrin is used.

Table 1. Dissociation constants of amino acids

Amino acid	pK 1	pK 2	pK 3
Alanya	2,34	9,69
Arginine	2,18	9,09	13,2
Asparagine	2,02	8,80
Aspartic acid	1,88	3,65	9,60
Wally	2,32	9,62
Histidine	1,78	5,97	8,97
Glycine	2,34	9,60
Glutamine	2,17	9,13
Glutamic acid	2,19	4,25	9,67
Isoleucine	2,26	9,62
Leucine	2,36	9,60
Lysine	2,20	8,90	10,28
Methionine	2,28	9,21
Proline	1,99	10,60
Series	2,21	9,15
Tyrosine	2,20	9,11	10,07
Threonine	2,15	9,12
tryptophan	2,38	9,39
Phenylalanine	1,83	9,13
Cysteine	1,71	8,33	10,78

STRUCTURAL ORGANIZATION OF PROTEINS

There are 4 main levels of structural organization of protein molecules.

Primary structure of a protein- the sequence of amino acid residues in the polypeptide chain. The individual amino acids in a protein molecule are linked to each other. peptide bonds, formed by the interaction of a-carboxyl and a-amino groups of amino acids:

.

At present, the primary structure of tens of thousands of different proteins has been deciphered. The first step in determining the primary structure of a protein is the determination of the amino acid composition by hydrolysis methods. Then determine chemical nature terminal amino acids. The next step is to determine the sequence of amino acids in the polypeptide chain, for which partial selective (enzymatic or chemical) hydrolysis is used.

The classification of amino acids was developed on the basis of chemical structure radicals. There are cyclic and aliphatic (acyclic) amino acids. According to the number of amine and carboxyl groups, amino acids are divided into:

1 - monoaminomonocarboxylic (glycine, alanine, leucine, etc.);

2 - diaminomonocarboxylic (lysine, arginine);

3 - monoaminodicarboxylic (aspartic and glutamic acids);

4-diaminodicarboxylic (cystine).

According to the nature of the charge of side radicals, their polarity, amino acids are classified into:

1 – non-polar, hydrophobic (glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan, tyrosine);

2 – polar, uncharged (serine, threonine, methionine, asparagine, glutamine, cysteine);

3 - polar, negatively charged (aspartic and glutamic acids,);

4 – polar, positively charged (lysine, arginine, histidine).

In α-amino acids, one can distinguish:

Anion groups: -SOO - ;

Cationic groups: -NH 3 + ; =NH + ; -NH-C=NH + 2;

Polar uncharged groups:-HE; -CONH 2 ; -SH;

Non-polar groups: -CH 3 , aliphatic chains, aromatic cycles (phenylalanine, tyrosine and tryptophan contain aromatic cycles).

Proline, unlike the other 19 amino acids, is not an amino acid, but an imino acid, the radical in proline is associated with both the α-carbon atom and the amino group:

NH-CH-COOH

Amino acids are distinguished by their solubility in water.. This is due to the ability of radicals to interact with water (hydrogenate).

TO hydrophilic include radicals containing anionic, cationic and polar uncharged functional groups.

TO hydrophobic include radicals containing methyl groups, aliphatic chains or cycles.

Peptide bonds link amino acids into peptides. The α-carboxyl group of one amino acid reacts with the α-amino group of another amino acid to form peptide bond.

NH 2 -CH-COOH + NH 2 -CH-COOH NH 2 -CH-CO- NH-CH-COOH

N-terminus peptide bond C-terminus

The polypeptide chains of proteins are polypeptides, the so-called. linear polymers of α-amino acids connected by a peptide bond. The amino acid monomers that make up polypeptides are called amino acid residues. The chain of repeating groups -NH-CH-CO- is called peptide backbone. An amino acid residue having a free α-amino group is called N-terminal, and one having a free α-carboxyl group is called C-terminal.

Peptides are written and read from the N-terminus !

Peptide bonds are very strong, and harsh conditions are required for their chemical non-enzymatic hydrolysis: high temperatures and pressure acidic environment and for a long time.

In a living cell, where there are no such conditions, peptide bonds can be broken by proteolytic enzymes called proteases or peptide hydrolases.

The presence of peptide bonds in a protein can be determined using the biuret reaction.

Free rotation in the peptide backbone is possible between the nitrogen atom of the peptide group and the neighboring α-carbon atom, as well as between the α-carbon atom and the carbonyl group carbon. Due to this, the linear structure can acquire a more complex spatial conformation.