The main amino acid is. "Amino acids structure, classification, properties, biological role

Proteins form the material basis of the chemical activity of the cell. The functions of proteins in nature are universal. Name proteins, most accepted in Russian literature, corresponds to the term proteins(from the Greek. proteios- first). To date, great success has been achieved in establishing the relationship between the structure and functions of proteins, the mechanism of their participation in the most important processes of the body's vital activity, and in understanding the molecular foundations of the pathogenesis of many diseases.

Depending on the molecular weight, peptides and proteins are distinguished. Peptides have a lower molecular weight than proteins. For peptides, a regulatory function is more characteristic (hormones, inhibitors and activators of enzymes, carriers of ions through membranes, antibiotics, toxins, etc.).

12.1. α -Amino acids

12.1.1. Classification

Peptides and proteins are built from α-amino acid residues. The total number of naturally occurring amino acids exceeds 100, but some of them are found only in a certain community of organisms, 20 of the most important α-amino acids are constantly found in all proteins (Scheme 12.1).

α-Amino acids are heterofunctional compounds, the molecules of which simultaneously contain an amino group and a carboxyl group at the same carbon atom.

Scheme 12.1.Essential α-amino acids *

* Abbreviations are used only for recording amino acid residues in peptide and protein molecules. ** Essential amino acids.

The names of α-amino acids can be constructed according to the substitutional nomenclature, but their trivial names are more often used.

The trivial names for α-amino acids are usually associated with the source of the excretion. Serine is a part of silk fibroin (from lat. serieus- silky); tyrosine was first isolated from cheese (from the Greek. tyros- cheese); glutamine - from cereal gluten (from it. Gluten- glue); aspartic acid - from asparagus sprouts (from lat. asparagus- asparagus).

Many α-amino acids are synthesized in the body. Some amino acids necessary for protein synthesis are not produced in the body and must be supplied from the outside. These amino acids are called irreplaceable(see diagram 12.1).

Essential α-amino acids include:

valine isoleucine methionine tryptophan

leucine lysine threonine phenylalanine

α-Amino acids are classified in several ways, depending on the trait underlying their division into groups.

One of the classification features is the chemical nature of the radical R. According to this feature, amino acids are divided into aliphatic, aromatic, and heterocyclic (see Scheme 12.1).

Aliphaticα -amino acids. This is the largest group. Inside it, amino acids are subdivided using additional classification features.

Depending on the number of carboxyl groups and amino groups in the molecule, the following are distinguished:

Neutral amino acids - one NH group each 2 and COOH;

Essential amino acids - two NH groups 2 and one group

UNOO;

Acidic amino acids - one NH 2 group and two COOH groups.

It can be noted that in the group of aliphatic neutral amino acids, the number of carbon atoms in the chain does not exceed six. At the same time, there is no amino acid with four carbon atoms in the chain, and amino acids with five and six carbon atoms have only a branched structure (valine, leucine, isoleucine).

The aliphatic radical may contain "additional" functional groups:

Hydroxyl - serine, threonine;

Carboxyl - aspartic and glutamic acids;

Thiol - cysteine;

Amide - asparagine, glutamine.

Aromaticα -amino acids. This group includes phenylalanine and tyrosine, constructed in such a way that the benzene rings in them are separated from the common α-amino acid fragment by the methylene group -CH 2-.

Heterocyclic α -amino acids. Histidine and tryptophan belonging to this group contain heterocycles - imidazole and indole, respectively. The structure and properties of these heterocycles are discussed below (see 13.3.1; 13.3.2). The general principle for the construction of heterocyclic amino acids is the same as for aromatic ones.

Heterocyclic and aromatic α-amino acids can be considered as β-substituted alanine derivatives.

Amino acid also belongs to heroic proline, in which the secondary amino group is included in the pyrrolidine

In the chemistry of α-amino acids, much attention is paid to the structure and properties of "side" radicals R, which play an important role in the formation of the structure of proteins and their performance of biological functions. Of great importance are characteristics such as the polarity of the "side" radicals, the presence of functional groups in the radicals, and the ability of these functional groups to ionize.

Depending on the side radical, amino acids with non-polar(hydrophobic) radicals and amino acids c polar(hydrophilic) radicals.

The first group includes amino acids with aliphatic side radicals - alanine, valine, leucine, isoleucine, methionine - and aromatic side radicals - phenylalanine, tryptophan.

The second group includes amino acids that have polar functional groups in the radical that are capable of ionization (ionogenic) or incapable of passing into an ionic state (nonionic) under the conditions of the organism. For example, in tyrosine the hydroxyl group is ionogenic (has a phenolic character), in serine it is nonionic (has an alcoholic nature).

Polar amino acids with ionogenic groups in radicals under certain conditions can be in the ionic (anionic or cationic) state.

12.1.2. Stereoisomerism

The basic type of construction of α-amino acids, that is, the bond of the same carbon atom with two different functional groups, a radical and a hydrogen atom, already predetermines the chirality of the α-carbon atom. The exception is the simplest amino acid glycine H 2 NCH 2 COOH without a chiral center.

The configuration of α-amino acids is determined according to the configuration standard - glyceraldehyde. The location in the standard projection Fischer formula of the amino group on the left (like the OH group in l-glycerol aldehyde) corresponds to the l-configuration, on the right - the d-configuration of the chiral carbon atom. By R, In the S-system, the α-carbon atom of all α-amino acids of the l-series has the S-, and the d-series has the R-configuration (the exception is cysteine, see 7.1.2).

Most α-amino acids contain one asymmetric carbon atom in the molecule and exist as two optically active enantiomers and one optically inactive racemate. Almost all natural α-amino acids belong to the l-series.

The amino acids isoleucine, threonine and 4-hydroxyproline contain two chiral centers in the molecule.

Such amino acids can exist as four stereoisomers, which are two pairs of enantiomers, each of which forms a racemate. For the construction of proteins of animal organisms, only one of the enantiomers is used.

The stereoisomerism of isoleucine is analogous to the previously discussed stereoisomerism of threonine (see 7.1.3). Of the four stereoisomers, proteins include l-isoleucine with the S-configuration of both asymmetric carbon atoms C-α and C-β. Another pair of enantiomers, which are diastereomeric with respect to leucine, use the prefix Hello-.

Cleavage of racemates. The source of obtaining α-amino acids of the l-series are proteins, which are subjected to hydrolytic cleavage for this purpose. Due to the great need for individual enantiomers (for the synthesis of proteins, medicinal substances, etc.), chemical methods for the cleavage of synthetic racemic amino acids. Preferred enzymatic digestion method using enzymes. At present, chromatography on chiral sorbents is used to separate racemic mixtures.

12.1.3. Acid-base properties

The amphotericity of amino acids is due to acidic (COOH) and basic (NH 2) functional groups in their molecules. Amino acids form salts with both alkalis and acids.

In the crystalline state, α-amino acids exist as dipolar ions H3N + - CHR-COO- (the commonly used notation

the structure of the amino acid in non-ionized form is only for convenience).

In aqueous solution, amino acids exist in the form of an equilibrium mixture of a dipolar ion, cationic and anionic forms.

The equilibrium position depends on the pH of the medium. All amino acids are dominated by cationic forms in strongly acidic (pH 1-2) and anionic forms in strongly alkaline (pH> 11) media.

The ionic structure determines a number of specific properties of amino acids: high melting point (above 200 ° C), solubility in water and insolubility in non-polar organic solvents. The ability of most amino acids to dissolve well in water is an important factor in ensuring their biological functioning; absorption of amino acids, their transport in the body, etc. are associated with it.

Fully protonated amino acid (cationic form) from the standpoint of Brønsted's theory is a diacid,

By donating one proton, such a dibasic acid turns into a weak monobasic acid - a dipolar ion with one acidic group NH 3 + . Deprotonation of the dipolar ion leads to the formation of the anionic form of the amino acid - the carboxylate ion, which is the Brønsted base. The values characterize

the acidic properties of the carboxyl group of amino acids usually range from 1 to 3; meaning pK a2 characterizing the acidity of the ammonium group - from 9 to 10 (Table 12.1).

Table 12.1.Acid-base properties of the most important α-amino acids

The equilibrium position, that is, the ratio of various forms of amino acids, in an aqueous solution at certain pH values depends significantly on the structure of the radical, mainly on the presence of ionogenic groups in it, which play the role of additional acidic and basic centers.

The pH value at which the concentration of dipolar ions is maximum, and the minimum concentrations of the cationic and anionic forms of the amino acid are equal, is calledisoelectric point (p /).

Neutralα -amino acids. These amino acids matterpIslightly lower than 7 (5.5-6.3) due to the greater ability to ionize the carboxyl group under the influence of the - / - effect of the NH 2 group. For example, alanine has an isoelectric point at pH 6.0.

Acidicα -amino acids. These amino acids have an additional carboxyl group in the radical and are in a fully protonated form in a strongly acidic medium. Acidic amino acids are tribasic (Brøndsted) with three meaningspK a,as can be seen from the example of aspartic acid (p / 3.0).

For acidic amino acids (aspartic and glutamic), the isoelectric point is much lower than pH 7 (see Table 12.1). In the body at physiological pH values (for example, blood pH 7.3-7.5), these acids are in the anionic form, since both carboxyl groups are ionized in them.

The mainα -amino acids. In the case of basic amino acids, the isoelectric points are in the pH range above 7. In a strongly acidic medium, these compounds are also tribasic acids, the stages of ionization of which are shown by the example of lysine (p / 9.8).

In the body, the main amino acids are in the form of cations, that is, both amino groups are protonated in them.

In general, no α-amino acid in vivois not at its isoelectric point and does not enter the state corresponding to the lowest solubility in water. All amino acids in the body are in ionic form.

12.1.4. Analytically important reactions α -amino acids

α-Amino acids as heterofunctional compounds enter into reactions characteristic of both carboxyl and amino groups. Some of the chemical properties of amino acids are due to the functional groups in the radical. This section discusses reactions that are of practical importance for the identification and analysis of amino acids.

Esterification.When amino acids react with alcohols in the presence of an acid catalyst (for example, gaseous hydrogen chloride), esters in the form of hydrochlorides are obtained in good yield. To isolate free ethers, the reaction mixture is treated with gaseous ammonia.

Esters of amino acids do not have a dipolar structure, therefore, unlike the original acids, they dissolve in organic solvents and are volatile. Thus, glycine is a crystalline substance with a high melting point (292 ° C), and its methyl ether is a liquid with a boiling point of 130 ° C. Amino acid esters can be analyzed by gas-liquid chromatography.

Reaction with formaldehyde. The reaction with formaldehyde, which underlies the quantitative determination of amino acids by the method formol titration(Sorensen method).

The amphotericity of amino acids does not allow direct titration with alkali for analytical purposes. The interaction of amino acids with formaldehyde gives relatively stable amino alcohols (see 5.3) - N-hydroxymethyl derivatives, the free carboxyl group of which is then titrated with alkali.

Qualitative reactions. The peculiarity of the chemistry of amino acids and proteins consists in the use of numerous qualitative (color) reactions, which previously formed the basis of chemical analysis. At present, when research is carried out using physicochemical methods, many qualitative reactions continue to be used for the detection of α-amino acids, for example, in chromatographic analysis.

Chelation. With cations of heavy metals, α-amino acids as bifunctional compounds form intracomplex salts, for example, with freshly prepared copper hydroxide (11) under mild conditions, well crystallizing chelate

blue copper (11) salts (one of the nonspecific methods for detecting α-amino acids).

Ninhydrine reaction. The general qualitative reaction of α-amino acids is the reaction with ninhydrin. The reaction product has a blue-violet color, which is used for visual detection of amino acids on chromatograms (on paper, in a thin layer), as well as for spectrophotometric determination on amino acid analyzers (the product absorbs light in the 550-570 nm region).

Deamination. Under laboratory conditions, this reaction is carried out by the action of nitrous acid on α-amino acids (see 4.3). In this case, the corresponding α-hydroxy acid is formed and gaseous nitrogen is released, by the volume of which the amount of the amino acid reacted is judged (Van Slike method).

Xanthoprotein reaction. This reaction is used to detect aromatic and heterocyclic amino acids - phenylalanine, tyrosine, histidine, tryptophan. For example, when concentrated nitric acid acts on tyrosine, a yellow-colored nitro derivative is formed. In an alkaline medium, the color turns orange due to ionization of the phenolic hydroxyl group and an increase in the contribution of the anion to the conjugation.

There are also a number of particular reactions that allow the detection of individual amino acids.

Tryptophan detected by reaction with p- (dimethylamino) benzaldehyde in a sulfuric acid medium by the appearing red-violet coloration (Ehrlich reaction). This reaction is used for the quantitative analysis of tryptophan in protein breakdown products.

Cysteine detected by several qualitative reactions based on the reactivity of the mercapto group contained therein. For example, when a protein solution with lead acetate (CH3COO) 2Pb is heated in an alkaline medium, a black precipitate of lead sulfide PbS is formed, which indicates the presence of cysteine in the proteins.

12.1.5. Biologically important chemical reactions

In the body, under the action of various enzymes, a number of important chemical transformations of amino acids are carried out. Such transformations include transamination, decarboxylation, elimination, aldol cleavage, oxidative deamination, and oxidation of thiol groups.

Transamination is the main pathway for the biosynthesis of α-amino acids from α-oxo acids. The donor of the amino group is the amino acid present in the cells in sufficient or excess amount, and its acceptor is the α-oxo acid. In this case, the amino acid is converted into an oxo acid, and the oxo acid into an amino acid with the corresponding structure of radicals. As a result, transamination is a reversible process of interchange of amino and oxo groups. An example of such a reaction is the production of l-glutamic acid from 2-oxoglutaric acid. The donor amino acid can be, for example, l-aspartic acid.

α-Amino acids contain in the α-position to the carboxyl group an electron-withdrawing amino group (more precisely, the protonated amino group NH 3 +), in this connection, they are capable of decarboxylation.

Eliminationcharacteristic of amino acids in which the side radical in the β-position to the carboxyl group contains an electron-withdrawing functional group, for example, hydroxyl or thiol. Their cleavage leads to intermediate reactive α-enamino acids, which are easily converted into tautomeric imino acids (analogy with keto-enol tautomerism). α-Imino acids, as a result of hydration at the C = N bond and subsequent elimination of the ammonia molecule, are converted into α-oxo acids.

This type of transformation is called elimination-hydration. An example is the preparation of pyruvic acid from serine.

Aldol cleavage occurs in the case of α-amino acids in which the β-position contains a hydroxyl group. For example, serine is cleaved to form glycine and formaldehyde (the latter is not released in free form, but immediately binds to the coenzyme).

Oxidative deamination can be carried out with the participation of enzymes and the coenzyme NAD + or NADP + (see 14.3). α-Amino acids can be converted to α-oxo acids not only through transamination, but also by oxidative deamination. For example, α-oxoglutaric acid is formed from l-glutamic acid. At the first stage of the reaction, the dehydrogenation (oxidation) of glutamic acid to α-iminoglutaric acid is carried out.

acid. In the second stage, hydrolysis occurs, as a result of which α-oxoglutaric acid and ammonia are obtained. The stage of hydrolysis proceeds without the participation of an enzyme.

The reaction of reductive amination of α-oxoacids proceeds in the opposite direction. The α-oxoglutaric acid always present in cells (as a product of carbohydrate metabolism) is converted in this way to L-glutamic acid.

Oxidation of thiol groups underlies the interconversion of cysteine and cystine residues, providing a number of redox processes in the cell. Cysteine, like all thiols (see 4.1.2), readily oxidizes to form a disulfide, cystine. The disulfide bond in cystine is easily reduced to form cysteine.

Due to the ability of the thiol group to easily oxidize, cysteine performs a protective function when exposed to substances with a high oxidizing capacity. In addition, it was the first drug to exhibit anti-radiation effects. Cysteine is used in pharmaceutical practice as a drug stabilizer.

The conversion of cysteine to cystine leads to the formation of disulfide bonds, for example, in reduced glutathione

(see 12.2.3).

12.2. Primary structure of peptides and proteins

Conventionally, it is believed that peptides contain up to 100 amino acids in a molecule (which corresponds to a molecular weight of up to 10 thousand), and proteins - more than 100 amino acid residues (molecular weight from 10 thousand to several million).

In turn, in the group of peptides, it is customary to distinguish oligopeptides(low molecular weight peptides) containing no more than 10 amino acid residues in the chain, and polypeptides, the chain of which includes up to 100 amino acid residues. Macromolecules with the number of amino acid residues approaching or slightly exceeding 100 do not distinguish between polypeptides and proteins, these terms are often used synonymously.

Formally, the peptide and protein molecule can be represented as a product of the polycondensation of α-amino acids, which proceeds with the formation of a peptide (amide) bond between monomer units (Scheme 12.2).

The construction of the polyamide chain is the same for the whole variety of peptides and proteins. This chain has an unbranched structure and consists of alternating peptide (amide) groups —CO — NH— and fragments —CH (R) -.

One end of the chain, which contains an amino acid with a free NH group 2, called the N-end, the other - the C-end,

Scheme 12.2.The principle of building a peptide chain

which contains an amino acid with a free COOH group. Peptide and protein chains are recorded from the N-terminus.

12.2.1. The structure of the peptide group

In the peptide (amide) group —CO — NH—, the carbon atom is in the state of sp2 hybridization. The lone pair of electrons of the nitrogen atom enters into conjugation with the π-electrons of the C = O double bond. From the standpoint of the electronic structure, the peptide group is a three-center p, π-conjugated system (see 2.3.1), in which the electron density is shifted towards the more electronegative oxygen atom. The atoms C, O, and N, forming a conjugated system, are in the same plane. The distribution of the electron density in the amide group can be represented using the boundary structures (I) and (II) or the shift of the electron density as a result of the + M- and - M-effects of the NH and C = O groups, respectively (III).

As a result of conjugation, some alignment of the bond lengths occurs. The C = O double bond is extended to 0.124 nm versus the usual length of 0.121 nm, and the C-N bond becomes shorter - 0.132 nm compared to 0.147 nm in the usual case (Fig. 12.1). The planar conjugated system in the peptide group is the reason for the difficulty of rotation around the C-N bond (the rotation barrier is 63-84 kJ / mol). Thus, the electronic structure predetermines a rather rigid flat the structure of the peptide group.

As can be seen from Fig. 12.1, the α-carbon atoms of amino acid residues are located in the plane of the peptide group on opposite sides of the C-N bond, i.e., in a more favorable trans-position: the side radicals R of amino acid residues in this case will be the farthest from each other in space.

The polypeptide chain has a surprisingly uniform structure and can be represented as a series of angled each

Rice. 12.1.Planar arrangement of the peptide group -CO-NH- and α-carbon atoms of amino acid residues

to another of the planes of peptide groups connected to each other through α-carbon atoms by bonds Сα-N and Сα-Сsp 2 (fig.12.2). Rotation around these single bonds is very limited due to difficulties in the spatial arrangement of side radicals of amino acid residues. Thus, the electronic and spatial structure of the peptide group largely determines the structure of the polypeptide chain as a whole.

Rice. 12.2.The relative position of the planes of peptide groups in the polypeptide chain

12.2.2. Composition and amino acid sequence

With a uniformly constructed polyamide chain, the specificity of peptides and proteins is determined by two most important characteristics - amino acid composition and amino acid sequence.

The amino acid composition of peptides and proteins is the nature and quantitative ratio of the α-amino acids included in them.

The amino acid composition is established by analyzing peptide and protein hydrolysates, mainly by chromatographic methods. Currently, this analysis is carried out using amino acid analyzers.

Amide bonds are capable of hydrolysis in both acidic and alkaline media (see 8.3.3). Peptides and proteins are hydrolyzed with the formation of either shorter chains - this is the so-called partial hydrolysis, or a mixture of amino acids (in ionic form) - complete hydrolysis. Usually, the hydrolysis is carried out in an acidic medium, since many amino acids are unstable under the conditions of alkaline hydrolysis. It should be noted that the amide groups of asparagine and glutamine also undergo hydrolysis.

The primary structure of peptides and proteins is the amino acid sequence, that is, the order of alternation of α-amino acid residues.

The primary structure is determined by sequential cleavage of amino acids from either end of the chain and their identification.

12.2.3. Structure and nomenclature of peptides

Peptide names are constructed by sequentially listing amino acid residues, starting from the N-terminus, with the addition of a suffix-il, except for the last C-terminal amino acid, for which its full name is retained. In other words, the names

amino acids that entered into the formation of a peptide bond due to their "own" COOH group end in the name of the peptide in -il: alanyl, valyl, etc. (the names “aspartyl” and “glutamyl” are used for the residues of aspartic and glutamic acids, respectively). The names and symbols of amino acids indicate their belonging to l -series, unless otherwise indicated ( d or dl).

Sometimes in the abbreviated notation with the symbols H (as part of the amino group) and OH (as part of the carboxyl group), the unsubstituted functional groups of terminal amino acids are specified. In this way, it is convenient to depict functional derivatives of peptides; for example, the C-terminal amino acid amide of the above peptide is written H-Asn-Gly-Phe-NH2.

Peptides are found in all organisms. Unlike proteins, they have a more heterogeneous amino acid composition, in particular, they quite often include amino acids d -series. Structurally, they are also more diverse: they contain cyclic fragments, branched chains, etc.

One of the most common representatives of tripeptides - glutathione- is found in the body of all animals, in plants and bacteria.

Cysteine in glutathione makes it possible for glutathione to exist in both reduced and oxidized forms.

Glutathione is involved in a number of redox processes. It acts as a protector of proteins, i.e., a substance that protects proteins with free SH thiol groups from oxidation with the formation of -S-S- disulfide bonds. This applies to those proteins for which such a process is undesirable. In these cases, glutathione takes over the action of an oxidizing agent and thus “protects” the protein. During the oxidation of glutathione, intermolecular crosslinking of two tripeptide fragments occurs due to a disulfide bond. The process is reversible.

12.3. Secondary structure of polypeptides and proteins

For high molecular weight polypeptides and proteins, along with the primary structure, higher levels of organization are also characteristic, which are called secondary, tertiary and quaternary structures.

The secondary structure is described by the spatial orientation of the main polypeptide chain, while the tertiary structure is described by the three-dimensional architecture of the entire protein molecule. Both secondary and tertiary structures are associated with the ordered arrangement of the macromolecular chain in space. The tertiary and quaternary structure of proteins is considered in the course of biochemistry.

It was shown by calculation that for the polypeptide chain one of the most favorable conformations is the arrangement in space in the form of a right-handed helix, called α-helix(Figure 12.3, a).

The spatial arrangement of the α-helical polypeptide chain can be imagined by imagining that it wraps around a certain

Rice. 12.3.α-Helical conformation of the polypeptide chain

cylinder (see Fig. 12.3, b). On average, there are 3.6 amino acid residues per turn of the helix, the helix pitch is 0.54 nm, and the diameter is 0.5 nm. In this case, the planes of two neighboring peptide groups are located at an angle of 108 °, and the side radicals of amino acids are located on the outer side of the helix, i.e., they are directed, as it were, from the surface of the cylinder.

The main role in fixing this chain conformation is played by hydrogen bonds, which in the α-helix are formed between the carbonyl oxygen atom of each first and the hydrogen atom of the NH-group of every fifth amino acid residue.

Hydrogen bonds are directed almost parallel to the axis of the α-helix. They keep the chain twisted.

Usually, protein chains are not completely spiralized, but only partially. Proteins such as myoglobin and hemoglobin contain rather long α-helical regions, such as a myoglobin chain

spiralized by 75%. In many other proteins, the proportion of helical regions in the chain may be small.

Another type of secondary structure of polypeptides and proteins is β-structure, also called folded sheet, or folded layer. Elongated polypeptide chains are laid in folded sheets, linked by many hydrogen bonds between the peptide groups of these chains (Fig. 12.4). Many proteins simultaneously contain α-helical and β-sheet structures.

Rice. 12.4.Secondary structure of the polypeptide chain in the form of a folded sheet (β-structure)

Modern protein nutrition cannot be imagined without considering the role of individual amino acids. Even with an overall positive protein balance, the animal's body may lack protein. This is due to the fact that the assimilation of individual amino acids is interconnected in each other, a deficiency or excess of one amino acid can lead to a deficiency of another.
Some amino acids are not synthesized in humans and animals. They are called irreplaceable. There are only ten such amino acids. Four of them are critical (limiting) - they most often limit the growth and development of animals.
In poultry diets, methionine and cystine are the main limiting amino acids, and lysine in pig diets. The body must receive a sufficient amount of the main limiting acid in food so that other amino acids can be effectively used for protein synthesis.

This principle is illustrated by the Liebig barrel, where the fill level of the barrel represents the level of protein synthesis in the animal's body. The shortest board in the barrel "limits" the ability to retain liquid. If this board is lengthened, then the volume of liquid retained in the barrel will increase to the level of the second limiting board.
The most important factor that determines the productivity of animals is the balance of the amino acids contained in it in accordance with physiological needs. Numerous studies have shown that in pigs, depending on the breed and sex, the need for amino acids differs quantitatively. But the ratio of essential amino acids for the synthesis of 1 g of protein is the same. This ratio of essential amino acids to lysine, as the main limiting amino acid, is called the “ideal protein” or “ideal amino acid profile”. (

Lysine

is a part of almost all proteins of animal, plant and microbial origin, however, the proteins of cereals are poor in lysine.

Lysine regulates the reproductive function, with its lack, the formation of sperm and eggs is impaired.
It is necessary for the growth of young animals, the formation of tissue proteins. Lysine takes part in the synthesis of nucleoproteins, chromoproteins (hemoglobin), thereby regulating the pigmentation of animal hair. Regulates the amount of protein breakdown products in tissues and organs.
Promotes Calcium Absorption
Participates in the functional activity of the nervous and endocrine systems, regulates the metabolism of proteins and carbohydrates, however, reacting with carbohydrates, lysine becomes inaccessible for assimilation.
Lysine is the precursor in the formation of carnitine, which plays an important role in fat metabolism.

Methionine and cystine sulfur-containing amino acids. In this case, methionine can be transformed into cystine, therefore, these amino acids are normalized together, and in case of a deficiency, methionine supplements are introduced into the diet. Both of these amino acids are involved in the formation of skin derivatives - hair, feather; together with vitamin E, they regulate the removal of excess fat from the liver, are necessary for the growth and multiplication of cells, erythrocytes. With a lack of methionine, cystine is inactive. However, a significant excess of methionine in the diet should not be allowed.

Methionine

promotes the deposition of fat in muscles, is necessary for the formation of new organic compounds of choline (vitamin B4), creatine, adrenaline, niacin (vitamin B5), etc.
Deficiency of methionine in diets leads to a decrease in the level of plasma proteins (albumin), causes anemia (decreases in the level of hemoglobin in the blood), with a simultaneous lack of vitamin E and selenium contributes to the development of muscular dystrophy. Insufficient methionine in the diet causes stunted growth of young animals, loss of appetite, decreased productivity, increased feed costs, fatty liver, renal impairment, anemia and wasting.
An excess of methionine impairs the use of nitrogen, causes degenerative changes in the liver, kidneys, pancreas, and increases the need for arginine and glycine. With a large excess of methionine, an imbalance is observed (the balance of amino acids is disturbed, which is based on sharp deviations from the optimal ratio of essential amino acids in the diet), which is accompanied by metabolic disorders and inhibition of the growth rate in young animals.
Cystine - a sulfur-containing amino acid, interchangeable with methionine, participates in redox processes, the metabolism of proteins, carbohydrates and bile acids, promotes the formation of substances that neutralize intestinal poisons, activates insulin, together with tryptophan, cystine participates in the synthesis of bile acids necessary for absorption in the liver products of digestion of fats from the intestines, used for the synthesis of glutathione. Cystine has the ability to absorb ultraviolet rays. With a lack of cystine, cirrhosis of the liver, a delay in feathering and feather growth in young animals, fragility and loss (plucking) of feathers in an adult bird, and a decrease in resistance to infectious diseases are noted.

Tryptophan

determines the physiological activity of digestive tract enzymes, oxidative enzymes in cells and a number of hormones, participates in the renewal of blood plasma proteins, determines the normal functioning of the endocrine and hematopoietic apparatus, the reproductive system, the synthesis of gamma - globulins, hemoglobin, nicotinic acid, eye purpura, etc. in the tryptophan diet, the growth of young animals slows down, the egg production of laying hens decreases, the cost of feed for production increases, the endocrine and gonads atrophy, blindness occurs, anemia develops (the number of red blood cells and hemoglobin level in the blood decreases), the resistance and immune properties of the body decrease, fertilization and hatchability of eggs ... In pigs fed a diet poor in tryptophan, feed intake decreases, perverted appetite, coarse bristles and emaciation appear, and fatty liver is noted. Deficiency of this amino acid also leads to sterility, increased excitability, convulsions, cataract formation, negative nitrogen balance and loss of body weight. Tryptophan, being a precursor (provitamin) of niacin, prevents the development of pellagra.

LIPIDS

Lipids are water-insoluble oily or fatty substances that can be extracted from cells with non-polar solvents. It is a heterogeneous group of compounds directly or indirectly associated with fatty acids.

Biological functions of lipids:

1) a source of energy that can be stored for a long time;

2) participation in the formation of cell membranes;

3) a source of fat-soluble vitamins, signaling molecules and essential fatty acids;

4) thermal insulation;

5) non-polar lipids serve as electrical insulators, providing rapid propagation of depolarization waves along myelinated nerve fibers;

6) participation in the formation of lipoproteins.

Fatty acids are the structural components of most lipids. These are long-chain organic acids containing 4 to 24 carbon atoms, they contain one carboxyl group and a long non-polar hydrocarbon "tail". In cells, they are not found in a free state, but only in a covalently bound form. Natural fats usually contain fatty acids with an even number of carbon atoms, since they are synthesized from bicarbon units that form an unbranched chain of carbon atoms. Many fatty acids have one or more double bonds - unsaturated fatty acids.

The most important fatty acids (after the formula are the number of carbon atoms, name, melting point):

12, lauric, 44.2 o C

14, myristic, 53.9 o C

16, palmitic, 63.1 o C

18, stearic, 69.6 o C

18, oleic, 13.5 about C

18, linoleic, -5 o C

18, linolenic, -11 o C

20, arachidonic, -49.5 o C

General properties of fatty acids;

Almost all contain an even number of carbon atoms,

Saturated acids in animals and plants are found twice as often as unsaturated ones,

Saturated fatty acids do not have a rigid linear structure, they are very flexible and can take on a variety of conformations,

In most fatty acids, the existing double bond is located between the 9th and 10th carbon atoms (Δ 9),

Additional double bonds are usually located between the Δ 9 double bond and the methyl end of the chain,

Two double bonds in fatty acids are not conjugated, there is always a methylene group between them,

Double bonds of almost all natural fatty acids are found in cis-conformation, which leads to a strong bending of the aliphatic chain and a more rigid structure,

At body temperature, saturated fatty acids are in a solid waxy state, and unsaturated fatty acids are liquids,

Sodium and potassium soaps of fatty acids are able to emulsify water-insoluble oils and fats, calcium and magnesium soaps of fatty acids dissolve very poorly and do not emulsify fats.

Unusual fatty acids and alcohols are found in the membrane lipids of bacteria. Many of the bacterial strains containing these lipids (thermophiles, acidophiles, and gallophils) are adapted to extreme conditions.

iso-branched

anti-branched

cyclopropane-containing

ω-cyclohexyl-containing

isopranial

cyclopentane phytanyl

The composition of bacterial lipids is very diverse, and the spectrum of fatty acids of different species has become a taxonomic criterion for identifying organisms.

In animals, the important derivatives of arachidonic acid are the histohormones prostaglandins, thromboxanes, and leukotrienes, combined into the eicosanoid group and possessing extremely broad biological activity.

prostaglandin H 2

Lipid classification:

1. Triacylglycerides(fats) are esters of an alcohol of glycerol and three fatty acid molecules. They constitute the main component of the fat depots of plant and animal cells. They are not contained in the membranes. Simple triacylglycerides contain residues of the same fatty acids in all three positions (tristearin, tripalmitin, triolein). Mixed contains different fatty acids. By specific gravity it is lighter than water, well soluble in chloroform, benzene, ether. Hydrolyzed by boiling with acids or bases, or by the action of lipase. In cells, under normal conditions, the self-oxidation of unsaturated fats is completely inhibited due to the presence of vitamin E, various enzymes and ascorbic acid. In specialized cells of the connective tissue of animal adipocytes, a huge amount of triacylglycerides can be stored in the form of fatty drops that fill almost the entire volume of the cell. In the form of glycogen, the body can store energy for no more than a day. Triacylglycerides can store energy for months, as they can be stored in very large quantities in an almost pure, unhydrated form and, per unit weight, they store twice as much energy as carbohydrates. In addition, triacylglycerides under the skin form an insulating layer that protects the body from the effects of very low temperatures.

neutral fat

The following constants are used to characterize the properties of fat:

Acid number - the amount of mg KOH required for neutralization

free fatty acids contained in 1 g of fat;

Saponification number - the amount of mg KOH required for hydrolysis

neutral lipids and neutralization of all fatty acids,

Iodine number - the number of grams of iodine associated with 100 g of fat,

characterizes the degree of unsaturation of a given fat.

2. Wax Are esters formed by long-chain fatty acids and long-chain alcohols. In vertebrates, waxes secreted by the skin glands act as a protective coating that lubricates and softens the skin and protects it from water. Hair, wool, fur, animal feathers, as well as leaves of many plants are covered with a wax layer. Waxes are produced and used in very large quantities by marine organisms, especially plankton, in which they serve as the main form of accumulation of high-calorie cellular fuel.

spermaceti, obtained from the brain of sperm whales

beeswax

3. Phosphoglycerolipids- serve as the main structural components of membranes and are never stored in large quantities. Necessarily contain in its composition polyhydric alcohol glycerin, phosphoric acid and residues of fatty acids.

Phosphoglycerolipids, according to their chemical structure, can be further divided into several types:

1) phospholipids - consist of glycerol, two fatty acid residues at the 1st and 2nd positions of glycerol and a phosphoric acid residue, with which the remainder of another alcohol is bound (ethanolamine, choline, serine, inositol). As a rule, the fatty acid in the 1st position is saturated, and in the 2nd it is unsaturated.

phosphatidic acid - a precursor for the synthesis of other phospholipids, it is contained in tissues in small amounts

phosphatidylethanolamine (cephalin)

phosphatidylcholine (lecithin), it is practically absent in bacteria

phosphatidylserine

phosphatidylinositol is a precursor of two important secondary messengers (intermediaries) of diacylglycerol and inositol-1,4,5-triphosphate

2) plasmalogens - phosphoglycerolipids, in which one of the hydrocarbon chains is a vinyl ether. Plasmalogens are not found in plants. Ethanolamine plasmalogens are widely present in myelin and in the sarcoplasmic reticulum of the heart.

ethanolamine plasma

3) lysophospholipids - are formed from phospholipids by enzymatic cleavage of one of the acyl residues. The snake venom contains phospholipase A 2, which forms lysophosphatides with hemolytic action;

4) cardiolipins - phospholipids of the inner membranes of bacteria and mitochondria, are formed by interaction with glycerol of two residues of phosphatidic acid:

cardiolipin

4. Phosphingolipids- the functions of glycerin in them are performed by sphingosine, an amino alcohol with a long aliphatic chain. Does not contain glycerin. They are present in large quantities in the membranes of cells of the nervous tissue and the brain. Phosphosphingolipids are rare in the membranes of plant and bacterial cells. Derivatives of sphingosine, acylated at the amino group with fatty acid residues, are called ceramides. The most important representative of this group is sphingomyelin (ceramide-1-phosphocholine). It is present in most membranes of animal cells, especially in the myelin sheaths of certain types of nerve cells.

sphingomyelin

sphingosine

5. Glycoglycerolipids - lipids in which in position 3 of glycerol there is a carbohydrate attached via a glycosidic bond do not contain a phosphate group. Glycoglycerolipids are widely found in chloroplast membranes, as well as in blue-green algae and bacteria. Monogalactosyldiacylglycerol is the most widespread polar lipid in nature, since it accounts for half of all lipids of the thylakoid membrane of chloroplasts:

monogalactosyldiacylglycerol

6. Glycosphingolipids- are built from sphingosine, a fatty acid residue and an oligosaccharide. Contained in all tissues, mainly in the outer lipid layer of plasma membranes. They lack a phosphate group and do not carry an electrical charge. Glycosphingolipids can be divided into two more types:

1) cerebrosides are simpler representatives of this group. Galactocerebrosides are found mainly in the membranes of brain cells, while glucocerebrosides are present in the membranes of other cells. Cerebrosides, containing two, three or four sugar residues, are localized mainly in the outer layer of cell membranes.

galactocerebroside

2) gangliosides are the most complex glycosphingolipids. Their very large polar heads are formed by several sugar residues. They are characterized by the presence in the extreme position of one or several residues of N-acetylneuraminic (sialic) acid, which carries a negative charge at pH 7. In the gray matter of the brain, gangliosides make up about 6% of membrane lipids. Gangliosides are important components of specific receptor sites located on the surface of cell membranes. So they are located in those specific areas of nerve endings where the binding of neurotransmitter molecules occurs in the process of chemical transmission of an impulse from one nerve cell to another.

7. Isoprenoids- isoprene derivatives (active form - 5-isopente-nyldiphosphate), performing a wide variety of functions.

isoprene 5-isopentenyl diphosphate

The ability to synthesize specific isoprenoids is characteristic of only some species of animals and plants.

1) rubber - several types of plants are synthesized, primarily Brazilian Hevea:

rubber fragment

2) fat-soluble vitamins A, D, E, K (due to structural and functional affinity with steroid hormones, vitamin D is now referred to as hormones):

vitamin A

vitamin E

vitamin K

3) animal growth hormones - retinoic acid in vertebrates and neoteinins in insects:

retinoic acid

neotenine

Retinoic acid is a hormonal derivative of vitamin A, stimulates the growth and differentiation of cells, neotenins are insect hormones, stimulate the growth of larvae and inhibit molting, are antagonists of ecdysone;

4) plant hormones - abscisic acid, is a stress phytohormone that triggers the systemic immune response of plants, manifested in resistance to a variety of pathogens:

abscisic acid

5) terpenes - numerous fragrant substances and essential oils of plants with bactericidal and fungicidal action; compounds of two isoprene units are called monoterpenes, of three - sesquiterpenes, of six - triterpenes:

camphor thymol

6) steroids are complex fat-soluble substances, the molecules of which basically contain cyclopentaneperhydrofenanthrene (in essence, triterpene). The main sterol in animal tissues is alcohol, cholesterol (cholesterol). Cholesterol and its esters with long-chain fatty acids are important components of plasma lipoproteins as well as the outer cell membrane. Because the four condensed rings create a rigid structure, the presence of cholesterol in membranes regulates membrane fluidity at extreme temperatures. Plants and microorganisms contain related compounds - ergosterol, stigmasterol and β-sitosterol.

cholesterol

ergosterol

stigmaster

β-sitosterol

Bile acids are formed from cholesterol in the body. They ensure the solubility of cholesterol in bile and aid in the digestion of lipids in the intestine.

cholic acid

Cholesterol also produces steroid hormones - lipophilic signaling molecules that regulate metabolism, growth and reproduction. In the human body, there are six main steroid hormones:

cortisol aldosterone

testosterone estradiol

progesterone calcitriol

Calcitriol is a hormonal vitamin D that differs from the hormones of vertebrates, but is also based on cholesterol. Ring B opens due to a light-dependent reaction.

A cholesterol derivative is the moulting hormone of insects, spiders and crustaceans - ecdysone. Signaling steroid hormones are also found in plants.

7) lipid anchors that hold molecules of proteins or other compounds on the membrane:

ubiquinone

As we can see, lipids are not polymers in the literal sense of the word, but both in metabolic and structural respects they are close to the polyoxybutyric acid present in bacteria, an important storage substance. This highly reduced polymer consists exclusively of ester-linked D-β-hydroxybutyric acid units. Each chain contains about 1500 residues. The structure is a compact right-hand helix, about 90 such chains are stacked to form a thin layer in bacterial cells.

poly-D-β-hydroxybutyric acid

Amino acids are carboxylic acids containing an amino group and a carboxyl group. Natural amino acids are 2-aminocarboxylic acids, or α-amino acids, although there are amino acids such as β-alanine, taurine, γ-aminobutyric acid. The generalized formula for an α-amino acid looks like this:

The α-amino acids at carbon 2 have four different substituents, that is, all α-amino acids, except for glycine, have an asymmetric (chiral) carbon atom and exist as two enantiomers - L- and D-amino acids. Natural amino acids belong to the L-series. D-amino acids are found in bacteria and peptide antibiotics.

All amino acids in aqueous solutions can exist in the form of bipolar ions, and their total charge depends on the pH of the medium. The pH value at which the net charge is zero is called the isoelectric point. At the isoelectric point, an amino acid is a zwitter ion, that is, its amine group is protonated, and the carboxyl group is dissociated. In the neutral pH range, most amino acids are zwitterions:

Amino acids do not absorb light in the visible region of the spectrum, aromatic amino acids absorb light in the UV region of the spectrum: tryptophan and tyrosine at 280 nm, phenylalanine at 260 nm.

Amino acids are characterized by some chemical reactions that are of great importance for laboratory practice: a colored ninhydrin test for the α-amino group, reactions characteristic of sulfhydryl, phenolic and other groups of amino acid radicals, acetalization and formation of Schiff bases by amino groups, esterification by carboxyl groups.

The biological role of amino acids:

1) are the structural elements of peptides and proteins, the so-called proteinogenic amino acids. The proteins include 20 amino acids, which are encoded by the genetic code and are included in proteins during translation, some of them can be phosphorylated, acylated or hydroxylated;

2) can be structural elements of other natural compounds - coenzymes, bile acids, antibiotics;

3) are signaling molecules. Some of the amino acids are neurotransmitters or precursors of neurotransmitters, hormones, and histohormones;

4) are the most important metabolites, for example, some amino acids are precursors of plant alkaloids, or serve as nitrogen donors, or are vital components of nutrition.

The classification of proteinogenic amino acids is based on the structure and polarity of the side chains:

1. Aliphatic amino acids:

glycine, glee, G, Gly

alanine, ala, A, Ala

valine, shaft, V, Val *

Leucine, lei, L, Leu *

isoleucine, silt, I, Ile *

These amino acids do not contain heteroatoms or cyclic groups in the side chain and are characterized by a pronounced low polarity.

cysteine, cis, C, Cys

methionine, meth, M, Met *

3. Aromatic amino acids:

phenylalanine, hair dryer, F, Phe *

tyrosine, shooting range, Y, Tyr

tryptophan, three, W, Trp *

histidine, gis, H, His

Aromatic amino acids contain mesomeric resonance stabilized cycles. In this group, only the amino acid phenylalanine exhibits low polarity, tyrosine and tryptophan are characterized by noticeable, and histidine - even high polarity. Histidine can also be referred to as basic amino acids.

4. Neutral amino acids:

serine, gray, S, Ser

threonine, tre, T, Thr *

asparagine, asn, N, Asn

glutamine, gln, Q, Gln

Neutral amino acids contain hydroxyl or carboxamide groups. Although the amide groups are nonionic, the asparagine and glutamine molecules are highly polar.

5. Acidic amino acids:

aspartic acid (aspartate), asp, D, Asp

glutamic acid (glutamate), deep, E, Glu

The carboxyl groups of the side chains of acidic amino acids are fully ionized over the entire physiological pH range.

6. Essential amino acids:

lysine, l from, K, Lys *

arginine, arg, R, Arg

The side chains of basic amino acids are fully protonated in the neutral pH range. A strongly basic and very polar amino acid is arginine, which contains a guanidine moiety.

7. Imino acid:

proline, about, P, Pro

The proline side chain consists of a five-membered ring containing an α-carbon atom and an α-amino group. Therefore, proline, strictly speaking, is not an amino acid, but an imino acid. The nitrogen atom in the ring is a weak base and is not protonated at physiological pH values. Due to its cyclic structure, proline causes bends in the polypeptide chain, which is very important for the structure of collagen.

Some of the listed amino acids cannot be synthesized in the human body and must be ingested with food. These essential amino acids are marked with asterisks.

As mentioned above, proteinogenic amino acids are precursors of some valuable biologically active molecules.

Two biogenic amines β-alanine and cysteamine are part of coenzyme A (coenzymes are derivatives of water-soluble vitamins that form the active center of complex enzymes). β-Alanine is formed by decarboxylation of aspartic acid, and cysteamine by decarboxylation of cysteine:

β-alanine cysteamine

The remainder of glutamic acid is part of another coenzyme - tetrahydrofolic acid, a derivative of vitamin B c.

Other biologically valuable molecules are conjugates of bile acids with the amino acid glycine. These conjugates are stronger acids than basic ones, are formed in the liver and are present in bile as salts.

glycocholic acid

Proteinogenic amino acids are precursors of some antibiotics - biologically active substances synthesized by microorganisms and inhibiting the growth of bacteria, viruses and cells. The most famous of them are penicillins and cephalosporins, which make up the group of β-lactam antibiotics and are produced by the mold of the genus Penicillium... They are characterized by the presence of a reactive β-lactam ring in the structure, with the help of which they inhibit the synthesis of the cell walls of gram-negative microorganisms.

general formula of penicillins

Biogenic amines - neurotransmitters, hormones and histohormones - are obtained from amino acids by decarboxylation.

The amino acids glycine and glutamate are themselves neurotransmitters in the central nervous system.

Alkaloids are also derivatives of amino acids - natural nitrogen-containing compounds of a basic nature, formed in plants. These compounds are extremely active physiological compounds widely used in medicine. Examples of alkaloids include the phenylalanine derivative papaverine, the isoquinoline alkaloid of hypnotic poppy (antispasmodic), and the tryptophan derivative physostigmine, an indole alkaloid from Calabar beans (anticholinesterase drug):

papaverine physostigmine

Amino acids are extremely popular biotechnology targets. There are many options for the chemical synthesis of amino acids, but the result is amino acid racemates. Since only L-isomers of amino acids are suitable for the food industry and medicine, racemic mixtures must be separated into enantiomers, which is a serious problem. Therefore, a biotechnological approach is more popular: enzymatic synthesis using immobilized enzymes and microbiological synthesis using whole microbial cells. In both the latter cases, pure L-isomers are obtained.

Amino acids are used as food additives and feed ingredients. Glutamic acid enhances the taste of meat, valine and leucine improve the taste of baked goods, glycine and cysteine are used as antioxidants in canning. D-tryptophan can be used as a sugar substitute as it is many times sweeter. Lysine is added to feed for farm animals, since most plant proteins contain a small amount of the essential amino acid lysine.

Amino acids are widely used in medical practice. These are such amino acids as methionine, histidine, glutamic and aspartic acids, glycine, cysteine, valine.

In the last decade, amino acids have begun to be added to cosmetics for skin and hair care.

Chemically modified amino acids are also widely used in industry as surfactants in the synthesis of polymers, in the production of detergents, emulsifiers, and fuel additives.

General characteristics (structure, classification, nomenclature, isomerism).

The main structural unit of proteins is a-amino acids. There are approximately 300 amino acids in nature. In the composition of proteins, 20 different a-amino acids have been found (one of them, proline, is not amino-, but imino acid). All other amino acids exist in a free state or in short peptides or complexes with other organic substances.

a-Amino acids are derivatives of carboxylic acids, in which one hydrogen atom, at the a-carbon atom is replaced by an amino group (–NH 2), for example:

Amino acids differ in the structure and properties of the radical R. The radical can represent residues of fatty acids, aromatic rings, heterocycles. Due to this, each amino acid is endowed with specific properties that determine the chemical, physical properties and physiological functions of proteins in the body.

It is thanks to amino acid radicals that proteins have a number of unique functions that are not characteristic of other biopolymers, and have a chemical identity.

Amino acids with the b- or g-position of the amino group are much less common in living organisms, for example:

Classification and nomenclature of amino acids.

There are several types of classifications of amino acids that make up the protein.

A) One of the classifications is based on the chemical structure of amino acid radicals. There are amino acids:

1. Aliphatic - glycine, alanine, valine, leucine, isoleucine:

2. Hydroxyl-containing - serine, threonine:

4. Aromatic - phenylalanine, tyrosine, tryptophan:

5.With anion-forming groups in the side chains - aspartic and glutamic acids:

6. and amides - aspartic and glutamic acids - asparagine, glutamine.

7. The main ones are arginine, histidine, lysine.

8. Imino acid - proline

B) The second type of classification is based on the polarity of the R-groups of amino acids.

Distinguish polar and non-polar amino acids. Nonpolar radicals have nonpolar C – C, C – H bonds, there are eight such amino acids: alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, proline.

All other amino acids are to polar(in the R-group there are polar bonds C – O, C – N, –OH, S – H). The more amino acids with polar groups in a protein, the higher its reactivity. Protein functions largely depend on the reactivity. Enzymes are characterized by a particularly large number of polar groups. Conversely, there are very few of them in such a protein as keratin (hair, nails).

B) Amino acids are also classified based on the ionic properties of the R-groups(Table 1).

Acidic(at pH = 7, the R-group can carry a negative charge) these are aspartic, glutamic acids, cysteine and tyrosine.

The main(at pH = 7, the R-group can carry a positive charge) is arginine, lysine, histidine.

All other amino acids belong to neutral (the R group is uncharged).

Table 1 - Classification of amino acids based on polarity
R-groups.

3. Negatively charged
R-groups

Aspartic acid

Glutamic acid

4. Positively charged
R-groups

Histidine

GLy ALa VaL Leu Lie Pro Phe Trp Ser Thr Cys Met Asn GLn Tyr Asp GLy Lys Arg His G A V L I P F W S T C M N Q Y D E K R N Gli Ala Val Lei Ile Pro Fen Trp Ser Tre Cis Met Asn Gln Tyr Asp Glu Liz Arg Gis 5,97 6,02 5,97 5,97 5,97 6,10 5,98 5,88 5,68 6,53 5,02 5,75 5,41 5,65 5,65 2,97 3,22 9,74 10,76 7,59 7,5 9,0 6,9 7,5 4,6 4,6 3,5 1,1 7,1 6,0 2,8 1,7 4,4 3,9 3,5 5,5 6,2 7,0 4,7 2,1

G) Amino acids are divided according to the number of amine and carboxyl groups:

– for monoamine monocarboxylic containing one carboxyl and one amine group;

- monoaminodicarboxylic(two carboxyl and one amine group);

- diaminomonocarboxylic(two amine and one carboxyl group).

E) According to the ability to be synthesized in the body of humans and animals, all amino acids are divided:

– replaceable,

- irreplaceable,

- partially irreplaceable.

Essential amino acids cannot be synthesized in humans and animals; they must be supplied with food. There are eight absolutely essential amino acids: valine, leucine, isoleucine, threonine, tryptophan, methionine, lysine, phenylalanine.

Partially irreplaceable - synthesized in the body, but in insufficient quantities, therefore, they must partially come from food. These amino acids are arganine, histidine, tyrosine.

Essential amino acids are synthesized in the human body in sufficient quantities from other compounds. Plants can synthesize all amino acids.

Isomerism

In the molecules of all natural amino acids (with the exception of glycine) at the a-carbon atom, all four valence bonds are occupied by various substituents, such a carbon atom is asymmetric, and is called chiral atom... As a result, amino acid solutions have optical activity - they rotate the plane of plane-polarized light. The number of possible stereoisomers is exactly 2 n, where n is the number of asymmetric carbon atoms. For glycine, n = 0, for threonine, n = 2. All the remaining 17 protein amino acids each contain one asymmetric carbon atom; they can exist in the form of two optical isomers.

As a standard in determining L and D-configurations of amino acids use the configuration of the stereoisomers of glyceraldehyde.

The location in the Fischer projection formula of the NH 2 -group on the left corresponds to L-configuration, and on the right - D-configurations.

It should be noted that the letters L and D denote the belonging of a particular substance by its stereochemical configuration to L or D row, regardless of the direction of rotation.

In addition to the 20 standard amino acids found in almost all proteins, there are also non-standard amino acids that are components of only some types of proteins - these amino acids are also called modified(hydroxyproline and hydroxylysine).

Methods of obtaining

- Amino acids are of extremely great physiological importance. Proteins and polypeptides are built from amino acid residues.

With the hydrolysis of protein substances animal and plant organisms are formed amino acids.

Synthetic methods for producing amino acids:

– The action of ammonia on halogenated acids

- α-Amino acids are obtained the action of ammonia on oxynitriles

Amino acids do not absorb light in the visible region of the spectrum, aromatic amino acids absorb light in the UV region of the spectrum: tryptophan and tyrosine at 280 nm, phenylalanine at 260 nm.

The biological role of amino acids:

2) can be structural elements of other natural compounds - coenzymes, bile acids, antibiotics;

3) are signaling molecules. Some of the amino acids are neurotransmitters or precursors of neurotransmitters, hormones, and histohormones;

4) are the most important metabolites, for example, some amino acids are precursors of plant alkaloids, or serve as nitrogen donors, or are vital components of nutrition.

The classification of proteinogenic amino acids is based on the structure and polarity of the side chains:

1. Aliphatic amino acids:

Glycine, glee, G, Gly

Alanin, ala, A, Ala

Valin, shaft, V, Val *

Leucine, lei, L, Leu *

Isoleucine, silt, I, Ile *

These amino acids do not contain heteroatoms or cyclic groups in the side chain and are characterized by a pronounced low polarity.

Cysteine, cis, C, Cys

Methionine, meth, M, Met *

3. Aromatic amino acids:

Phenylalanine, hair dryer, F, Phe *

Tyrosine, shooting range, Y, Tyr

Tryptophan, three, W, Trp *

Histidine, gis, H, His

4. Neutral amino acids:

Serin, gray, S, Ser

Threonine, tre, T, Thr *

Asparagin, asn, N, Asn

Glutamine, gln, Q, Gln

Neutral amino acids contain hydroxyl or carboxamide groups. Although the amide groups are nonionic, the asparagine and glutamine molecules are highly polar.

5. Acidic amino acids:

Aspartic acid (aspartate), asp, D, Asp

Glutamic acid (glutamate), deep, E, Glu

The carboxyl groups of the side chains of acidic amino acids are fully ionized over the entire physiological pH range.

6. Essential amino acids:

Lysine, l from, K, Lys *

Arginine, arg, R, Arg

The side chains of basic amino acids are fully protonated in the neutral pH range. A strongly basic and very polar amino acid is arginine, which contains a guanidine moiety.

7. Imino acid:

Proline, about, P, Pro

Some of the listed amino acids cannot be synthesized in the human body and must be ingested with food. These essential amino acids are marked with asterisks.

As mentioned above, proteinogenic amino acids are precursors of some valuable biologically active molecules.

β-alanine cysteamine

The remainder of glutamic acid is part of another coenzyme - tetrahydrofolic acid, a derivative of vitamin B c.

Glycocholic acid

General formula of penicillins

Biogenic amines - neurotransmitters, hormones and histohormones - are obtained from amino acids by decarboxylation.

The amino acids glycine and glutamate are themselves neurotransmitters in the central nervous system.

dopamine (neurotransmitter) norepinephrine (neurotransmitter)

adrenaline (hormone) histamine (neurotransmitter and histohormone)

serotonin (neurotransmitter and histohormone) GABA (neurotransmitter)

Thyroxine (hormone)

The derivative of the amino acid tryptophan is the best known naturally occurring auxin - indoleacetic acid. Auxins are plant growth regulators, they stimulate the differentiation of growing tissues, the growth of cambium, roots, accelerate the growth of fruits and the shedding of old leaves, their antagonists are abscisic acid.

Indoleacetic acid

papaverine physostigmine

Amino acids are widely used in medical practice. These are such amino acids as methionine, histidine, glutamic and aspartic acids, glycine, cysteine, valine.

In the last decade, amino acids have begun to be added to cosmetics for skin and hair care.

Chemically modified amino acids are also widely used in industry as surfactants in the synthesis of polymers, in the production of detergents, emulsifiers, and fuel additives.

PROTEINS

Proteins are high molecular weight substances composed of amino acids linked by a peptide bond.

It is proteins that are the product of genetic information transmitted from generation to generation, and carry out all vital processes in the cell.

Protein functions:

1. Catalytic function. The most numerous group of proteins are enzymes - proteins with catalytic activity that accelerate chemical reactions. Examples of enzymes are pepsin, alcohol dehydrogenase, glutamine synthetase.

2. Structural function. Structural proteins are responsible for maintaining the shape and stability of cells and tissues, these include keratins, collagen, fibroin.

3. Transport function. Transport proteins transport molecules or ions from one organ to another or across membranes within a cell, for example, hemoglobin, serum albumin, ion channels.

4. Protective function. The proteins of the homeostasis system protect the body from pathogens, foreign information, blood loss - immunoglobulins, fibrinogen, thrombin.

5. Regulatory function. Proteins carry out the functions of signaling substances - some hormones, histohormones and neurotransmitters, are receptors for signaling substances of any structure, provide further signal transmission in the biochemical signaling chains of the cell. Examples include growth hormone somatotropin, hormone insulin, H- and M-cholinergic receptors.

6. Motor function. With the help of proteins, the processes of contraction and other biological movement are carried out. Examples include tubulin, actin, myosin.

7. Spare function. Plants contain storage proteins, which are valuable nutrients; in animal organisms, muscle proteins serve as reserve nutrients that are mobilized when absolutely necessary.

Proteins are characterized by the presence of several levels of structural organization.

Primary structure protein refers to the sequence of amino acid residues in the polypeptide chain. A peptide bond is a carboxamide bond between the α-carboxyl group of one amino acid and the α-amino group of another amino acid.

Alanylphenylalanylcysteylproline

The peptide bond has several characteristics:

a) it is resonantly stabilized and therefore is practically in the same plane - planar; rotation around the C-N bond requires a lot of energy and is difficult;

b) the -CO-NH- bond has a special character, it is less than usual, but more than double, that is, there is keto-enol tautomerism:

c) substituents in relation to the peptide bond are in trance-position;

d) the peptide backbone is surrounded by side chains of various nature, interacting with the surrounding solvent molecules, free carboxyl and amino groups are ionized, forming cationic and anionic centers of the protein molecule. Depending on their ratio, the protein molecule receives a total positive or negative charge, and is also characterized by a particular pH value of the medium upon reaching the isoelectric point of the protein. Radicals form salt, ether, disulfide bridges within the protein molecule, and also determine the range of reactions inherent in proteins.

At present, we have agreed to consider polymers consisting of 100 or more amino acid residues as proteins, polypeptides - polymers consisting of 50-100 amino acid residues, low molecular weight peptides - polymers consisting of less than 50 amino acid residues.

Some low molecular weight peptides play an independent biological role. Examples of some of these peptides:

Glutathione - γ-glu-cis-gly - one of the most widespread intracellular peptides, is involved in redox processes in cells and the transfer of amino acids across biological membranes.

Carnosine - β-ala-gis - a peptide contained in the muscles of animals, eliminates the products of lipid peroxide breakdown, accelerates the breakdown of carbohydrates in muscles and is involved in energy metabolism in muscles in the form of phosphate.

Vasopressin is a hormone of the posterior lobe of the pituitary gland, which is involved in the regulation of water metabolism in the body:

Phalloidin is a poisonous fly agaric polypeptide, in negligible concentrations, causes the death of the body due to the release of enzymes and potassium ions from the cells:

Gramicidin is an antibiotic that acts on many gram-positive bacteria, changes the permeability of biological membranes for low molecular weight compounds and causes cell death:

Met-enkephalin - tyr-gli-gli-phen-meth - a peptide synthesized in neurons and weakening pain.

Secondary protein structure Is a spatial structure formed as a result of interactions between functional groups of the peptide backbone.

The peptide chain contains many CO and NH groups of peptide bonds, each of which is potentially capable of participating in the formation of hydrogen bonds. There are two main types of structures that allow this to be done: the α-helix, in which the chain coils like a cord from a telephone receiver, and the folded β-structure, in which stretched sections of one or more chains are laid side by side. Both of these structures are very stable.

The α-helix is characterized by extremely tight packing of the twisted polypeptide chain, for each turn of the right-handed helix there are 3.6 amino acid residues, the radicals of which are always directed outward and slightly backward, that is, to the beginning of the polypeptide chain.

The main characteristics of the α-helix:

1) the α-helix is stabilized by hydrogen bonds between the hydrogen atom at the nitrogen of the peptide group and the carbonyl oxygen of the residue, which is four positions apart from the given one along the chain;

2) all peptide groups are involved in the formation of a hydrogen bond, this ensures maximum stability of the α-helix;

3) all nitrogen and oxygen atoms of peptide groups are involved in the formation of hydrogen bonds, which significantly reduces the hydrophilicity of the α-helical regions and increases their hydrophobicity;

4) the α-helix is formed spontaneously and is the most stable conformation of the polypeptide chain, which corresponds to the minimum of free energy;

5) in the polypeptide chain of L-amino acids, the right helix, usually found in proteins, is much more stable than the left one.

The possibility of α-helix formation is due to the primary structure of the protein. Some amino acids prevent the curling of the peptide backbone. For example, adjacent carboxyl groups of glutamate and aspartate mutually repel each other, which prevents the formation of hydrogen bonds in the α-helix. For the same reason, the spiralization of the chain is hindered at the sites of closely spaced positively charged lysine and arginine residues. However, proline plays the greatest role in the disruption of the α-helix. Firstly, in proline, the nitrogen atom is part of a rigid ring, which prevents rotation around the N-C bond, and secondly, proline does not form a hydrogen bond due to the absence of hydrogen at the nitrogen atom.

β-folding is a layered structure formed by hydrogen bonds between linearly located peptide fragments. Both chains can be independent or belong to the same polypeptide molecule. If the chains are oriented in one direction, then such a β-structure is called parallel. In the case of the opposite direction of the chains, that is, when the N-end of one chain coincides with the C-end of the other chain, the β-structure is called antiparallel. Energetically, antiparallel β-folding with almost linear hydrogen bridges is more preferable.

parallel β-folding anti-parallel β-folding

In contrast to the α-helix saturated with hydrogen bonds, each section of the β-folding chain is open for the formation of additional hydrogen bonds. Lateral amino acid radicals are oriented almost perpendicular to the plane of the sheet, alternately up and down.

In those regions where the peptide chain bends rather abruptly, there is often a β-loop. This is a short fragment in which 4 amino acid residues are bent by 180 ° and stabilized by one hydrogen bridge between the first and fourth residues. Large amino acid radicals interfere with the formation of the β-loop, therefore, the smallest amino acid glycine is most often included in it.

Protein supersecondary structure- this is some specific order of alternation of secondary structures. A domain is understood as a separate part of a protein molecule that has a certain degree of structural and functional autonomy. Domains are now considered fundamental elements of the structure of protein molecules, and the ratio and nature of the arrangement of α-helices and β-layers provides more for understanding the evolution of protein molecules and phylogenetic relationships than a comparison of primary structures. The main task of evolution is the construction of all new proteins. The chance is infinitely small to accidentally synthesize an amino acid sequence that would satisfy the packaging conditions and ensure the performance of functional tasks. Therefore, proteins with different functions are often found, but similar in structure so much that it seems that they had one common ancestor or descended from each other. It seems that evolution, faced with the need to solve a certain problem, prefers not to design proteins for this first, but to adapt for this already well-oiled structures, adapting them for new purposes.

Some examples of frequently repeated supersecondary structures:

1) αα ’- proteins containing only α-helices (myoglobin, hemoglobin);

2) ββ '- proteins containing only β-structures (immunoglobulins, superoxide dismutase);

3) βαβ ’- the structure of the β-barrel, each β-layer is located inside the barrel and is associated with the α-helix located on the surface of the molecule (triose phosphoisomerase, lactate dehydrogenase);

4) "zinc finger" - a protein fragment consisting of 20 amino acid residues, the zinc atom is linked to two cysteine and two histidine residues, resulting in the formation of a "finger" of about 12 amino acid residues, can bind to the regulatory regions of the DNA molecule;

5) "leucine zipper" - interacting proteins have an α-helical region containing at least 4 leucine residues, they are located 6 amino acids apart, that is, they are on the surface of every second turn and can form hydrophobic bonds with leucine residues another protein. With the help of leucine fasteners, for example, molecules of highly basic proteins of histones can combine into complexes, overcoming the positive charge.

Protein tertiary structure Is the spatial arrangement of a protein molecule, stabilized by bonds between amino acid side radicals.

Types of bonds that stabilize the tertiary structure of a protein:

electrostatic hydrogen hydrophobic disulfide

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Depending on the folding of the tertiary structure, proteins can be classified into two main types - fibrillar and globular.

Fibrillar proteins are long filamentous molecules insoluble in water, the polypeptide chains of which are extended along one axis. These are mainly structural and contractile proteins. A few examples of the most common fibrillar proteins:

1. α-Keratins. Synthesized by cells of the epidermis. They account for almost all the dry weight of hair, fur, feathers, horns, nails, claws, needles, scales, hooves and turtle shell, as well as a significant part of the weight of the outer layer of the skin. This is a whole family of proteins, they are similar in amino acid composition, contain many cysteine residues and have the same spatial arrangement of polypeptide chains. In hair cells, keratin polypeptide chains are first organized into fibers, from which structures are then formed like a rope or a twisted cable, which eventually fills the entire space of the cell. At the same time, the hair cells become flattened and finally die off, and the cell walls form a tubular sheath around each hair, called the cuticle. In α-keratin, the polypeptide chains have the shape of an α-helix, twisted around one another into a three-core cable with the formation of transverse disulfide bonds. N-terminal residues are located on one side (parallel). Keratins are insoluble in water due to the predominance of amino acids with non-polar side radicals in their composition, which are directed towards the aqueous phase. During perm, the following processes take place: first, by reduction with thiols, disulfide bridges are destroyed, and then, when the hair is given the required shape, they are dried by heating, while new disulfide bridges are formed due to oxidation with air oxygen, which retain the shape of the hairstyle.

2. β-Keratins. These include silk and web fibroin. They are antiparallel β-folded layers with a predominance of glycine, alanine and serine in the composition.

3. Collagen. The most abundant protein in higher animals and the main fibrillar protein of connective tissues. Collagen is synthesized in fibroblasts and chondrocytes - specialized cells of connective tissue, from which it is then expelled. Collagen fibers are found in skin, tendons, cartilage and bones. They do not stretch, surpass steel wire in strength, collagen fibrils are characterized by transverse striation. When boiled in water, fibrous, insoluble and indigestible collagen turns into gelatin as a result of hydrolysis of some covalent bonds. Collagen contains 35% glycine, 11% alanine, 21% proline and 4-hydroxyproline (an amino acid found only in collagen and elastin). This composition determines the relatively low nutritional value of gelatin as a food protein. Collagen fibrils are composed of repeating polypeptide subunits called tropocollagen. These subunits are stacked along the fibril in parallel head-to-tail bundles. The displacement of the heads gives the characteristic transverse striation. Voids in this structure, if necessary, can serve as a place for the deposition of crystals of hydroxyapatite Ca 5 (OH) (PO 4) 3, which plays an important role in bone mineralization.

Tropocollagen subunits consist of three polypeptide chains tightly twisted in the form of a three-strand rope, distinct from α- and β-keratins. In some collagens, all three chains have the same amino acid sequence, while in others, only two chains are identical, and the third differs from them. The tropocollagen polypeptide chain forms a left helix with only three amino acid residues per turn due to the chain bends caused by proline and hydroxyproline. In addition to hydrogen bonds, the three chains are linked together by a covalent bond formed between two lysine residues located in adjacent chains:

As we get older, more and more cross-links are formed in and between tropocollagen subunits, which makes collagen fibrils more rigid and fragile, and this changes the mechanical properties of cartilage and tendons, makes bones more fragile and reduces the transparency of the cornea of the eye.

4. Elastin. It is contained in the yellow elastic tissue of the ligaments and the elastic layer of connective tissue in the walls of large arteries. The main subunit of elastin fibrils is tropoelastin. Elastin is rich in glycine and alanine, high in lysine and low in proline. The spiral sections of elastin stretch under tension, but return to their original length when the load is removed. Lysine residues from four different chains form covalent bonds with each other and allow elastin to stretch reversibly in all directions.

Globular proteins - proteins, the polypeptide chain of which is folded into a compact globule, capable of performing a wide variety of functions.

It is most convenient to consider the tertiary structure of globular proteins using myoglobin as an example. Myoglobin is a relatively small oxygen-binding protein found in muscle cells. It stores bound oxygen and promotes its transfer to mitochondria. The myoglobin molecule contains one polypeptide chain and one hemogroup (heme) - a complex of protoporphyrin with iron. The main properties of myoglobin:

a) the myoglobin molecule is so compact that only 4 water molecules can fit inside it;

b) all polar amino acid residues, with the exception of two, are located on the outer surface of the molecule, and all of them are in a hydrated state;

c) most of the hydrophobic amino acid residues are located inside the myoglobin molecule and, thus, protected from contact with water;

d) each of the four proline residues in the myoglobin molecule is located at the bend of the polypeptide chain, in other places of the bend there are serine, threonine and asparagine residues, since such amino acids prevent the formation of an α-helix if they are with each other;

e) the planar hemogroup lies in the cavity (pocket) near the surface of the molecule, the iron atom has two coordination bonds directed perpendicular to the heme plane, one of them is associated with the histidine residue 93, and the other serves to bind the oxygen molecule.

Starting from the tertiary structure, the protein becomes capable of performing its inherent biological functions. The functioning of proteins is based on the fact that when the tertiary structure is folded on the surface of the protein, regions are formed that can attach other molecules, called ligands. The high specificity of the interaction of the protein with the ligand is provided by the complementarity of the structure of the active center to the structure of the ligand. Complementarity is the spatial and chemical conformity of interacting surfaces. For most proteins, the tertiary structure is the maximum level of folding.

Quaternary protein structure- is typical for proteins consisting of two or more polypeptide chains linked by exclusively non-covalent bonds, mainly electrostatic and hydrogen. Most often, proteins contain two or four subunits, more than four subunits usually contain regulatory proteins.

Proteins with a quaternary structure are often called oligomeric. Distinguish between homomeric and heteromeric proteins. Homomeric proteins include proteins in which all subunits have the same structure, for example, the catalase enzyme consists of four absolutely identical subunits. Heteromeric proteins have different subunits, for example, the RNA polymerase enzyme consists of five structurally different subunits that perform different functions.

The interaction of one subunit with a specific ligand causes conformational changes in the entire oligomeric protein and changes the affinity of other subunits for ligands; this property underlies the ability of oligomeric proteins for allosteric regulation.

The quaternary structure of a protein can be considered using the example of hemoglobin. Contains four polypeptide chains and four prosthetic heme groups, in which iron atoms are in the ferrous form Fe 2+. The protein part of the molecule - globin - consists of two α-chains and two β-chains, containing up to 70% of α-helices. Each of the four chains has a characteristic tertiary structure, with each chain associated with one hemogroup. The hemes of different chains are relatively far apart and have a different angle of inclination. There are few direct contacts between the two α-chains and two β-chains, while between the α- and β-chains there are numerous contacts of the α 1 β 1 and α 2 β 2 type formed by hydrophobic radicals. A channel remains between α 1 β 1 and α 2 β 2.

Unlike myoglobin, hemoglobin is characterized by a significantly lower affinity for oxygen, which allows it to give them a significant part of the bound oxygen at the low partial pressures of oxygen existing in the tissues. Oxygen is more easily bound by the iron of hemoglobin at higher pH values and low CO 2 concentration, characteristic of the alveoli of the lungs; the release of oxygen from hemoglobin is favored by lower pH values and high CO 2 concentrations inherent in tissues.

In addition to oxygen, hemoglobin carries hydrogen ions, which bind to histidine residues in the chains. Hemoglobin also carries carbon dioxide, which attaches to the terminal amino group of each of the four polypeptide chains, resulting in the formation of carbaminohemoglobin:

In erythrocytes, the substance 2,3-diphosphoglycerate (DPG) is present in sufficiently high concentrations, its content increases when rising to a great height and during hypoxia, facilitating the release of oxygen from hemoglobin in tissues. DPG is located in the channel between α 1 β 1 and α 2 β 2, interacting with positively infected groups of β-chains. When oxygen is bound by hemoglobin, DPG is displaced from the cavity. The erythrocytes of some birds do not contain DPG, but inositol hexa-phosphate, which further reduces the affinity of hemoglobin for oxygen.

2,3-diphosphoglycerate (DPG)

HbA - normal adult hemoglobin, HbF - fetal hemoglobin, has a greater affinity for O 2, HbS - hemoglobin in sickle cell anemia. Sickle cell anemia is a serious hereditary disorder associated with a genetic abnormality in hemoglobin. An unusually large number of thin sickle-shaped erythrocytes is observed in the blood of sick people, which, firstly, easily rupture, and secondly, clog the blood capillaries. At the molecular level, hemoglobin S differs from hemoglobin A by one amino acid residue at position 6 of the β-chains, where valine is found instead of the glutamic acid residue. Thus, hemoglobin S contains two negative charges less, the appearance of valine leads to the appearance of a "sticky" hydrophobic contact on the surface of the molecule, as a result, during deoxygenation, deoxyhemoglobin S molecules stick together and form insoluble abnormally long filamentous aggregates leading to deformation of erythrocytes.

There is no reason to believe that there is independent genetic control over the formation of levels of protein structural organization above the primary, since the primary structure determines both the secondary, and tertiary, and quaternary (if any). The native conformation of the protein is the thermodynamically most stable structure under these conditions.