Chemical elements necessarily included in a protein molecule. Protein composition: what do we know about it? Initial stages in protein chemistry

Amino acids - structural components proteins.Proteins, or proteins(Greek protos - primary) are biological heteropolymers, the monomers of which are amino acids.

Amino acids are low molecular weight organic compounds containing carboxyl (-COOH) and amine (-NH 2) groups that are bonded to the same carbon atom. A side chain is attached to the carbon atom - a radical that gives each amino acid certain properties. The general formula of amino acids is:

Most amino acids have one carboxyl group and one amino group; these amino acids are called neutral. There are, however, also basic amino acids- with more than one amino group, as well as acidic amino acids- with more than one carboxyl group.

There are about 200 amino acids known to be found in living organisms, but only 20 of them are found in proteins. These are the so-called basic, or protein-forming(proteinogenic), amino acids.

Depending on the type of radical, basic amino acids are divided into three groups: 1) non-polar (alanine, methionine, valine, proline, leucine, isoleucine, tryptophan, phenylalanine); 2) polar uncharged (asparagine, glutamine, series, glycine, tyrosine, threonine, cysteine); 3) polar charged (arginine, histidine, lysine - positive; aspartic and glutamic acids - negative).

The side chains of amino acids (radical) can be hydrophobic or hydrophilic, which gives proteins the corresponding properties that are manifested in the formation of secondary, tertiary and quaternary protein structures.

In plants All essential amino acids are synthesized from the primary products of photosynthesis. Humans and animals are not able to synthesize a number of proteinogenic amino acids and must receive them in finished form with food. These amino acids are called irreplaceable. TO these include lysine, valine, leucine, isoleucine, threonine, phenylalanine, tryptophan, methionine; as well as arginine and histidine - essential for children,

In solution, amino acids can act as both acids and bases, i.e. they are amphoteric compounds. The carboxyl group -COOH is capable of donating a proton, functioning as an acid, and the amino group - NH2 - can accept a proton, thus exhibiting the properties of a base.

Peptides. The amino group of one amino acid can react with the carboxyl group of another amino acid.

The resulting molecule is a dipeptide, and the -CO-NH- bond is called a peptide bond:

At one end of the dipeptide molecule there is a free amino group, and at the other there is a free carboxyl group. Thanks to this, the dipeptide can attach other amino acids to itself, forming oligopeptides. If many amino acids are combined in this way (more than ten), then it turns out polypeptide.

Peptides play an important role in the body. Many oligo- and polypeptides are hormones, antibiotics, and toxins.

Oligopeptides include oxytocin, vasopressin, thyrotropin, as well as bradykinin (pain peptide) and some opiates (human “natural drugs”) that act as pain relievers. Taking drugs destroys the body's opiate system, so an addict without a dose of drugs experiences severe pain - “withdrawal”, which is normally relieved by opiates. Some antibiotics (for example, gramicidin S) also belong to oligopeptides.

Many hormones (insulin, adrenocorticotropic hormone, etc.), antibiotics (for example, gramicidin A), toxins (for example, diphtheria toxin) are polypeptides.

Proteins are polypeptides, the molecule of which contains from fifty to several thousand amino acids with a relative molecular weight of over 10,000.

Structure of proteins. Each protein in a certain environment is characterized by a special spatial structure. When characterizing the spatial (three-dimensional) structure, four levels of organization of protein molecules are distinguished (Fig. 1.1).

lie-glu-tre-ala-ala-ala-liz-fen-glu-arg-gln-gis-met-asp-ser-
ser-tre-ser-ala-ala-ser-ser-ser-asn-tir-cis-asn-glu-met-met-
lis-ser-arg-asn-ley-tre-lys-asp-arg-cis-lys-pro-val-asn-tre-
fen--val-gis-glu-ser-ley-ala-asp-val-gln-ala-val-cis-ser-gln-
lys—asn—val—ala—cis—lys—asn—gli—gln—tre—asn—cis—tri—gln—ser—
tri-ser-tre-met-ser-ile-tre-asp-cis-arg-glu-tre-gli-ser-ser-
lie-tir-pro-asn-cis-ala-tir-lie-tre-tre-gln-ala-asn-liz-gis-
ile-ile-val-ala-cis-glu-gli-asn-pro-tir-val-pro-val-gis-fen-
asp-ala-ser-val

Rice. 1.1. Levels of protein structural organization: a — primary structure - amino acid sequence of protein ribonuclease (124 amino acid units); b — secondary structure — the polypeptide chain is twisted in the form of a spiral; V— tertiary structure of myoglobin protein; G — quaternary structure of hemoglobin.

Primary structure— the sequence of amino acids in a polypeptide chain. This structure is specific to each protein and is determined by genetic information, that is, it depends on the sequence of nucleotides in the section of the DNA molecule encoding the given protein. All properties and functions of proteins depend on the primary structure. Replacement of a single amino acid in the composition of protein molecules or disruption of their arrangement usually entails a change in the function of the protein.

Considering that proteins contain 20 types of amino acids, the number of options for their combinations in the polypeptide chain is truly limitless, which provides a huge number of types of proteins in living cells. For example, more than 10 thousand different proteins have been found in the human body, and they are all built from the same 20 basic amino acids.

In living cells, protein molecules or individual sections of them are not an elongated chain, but are twisted into a spiral, reminiscent of an extended spring (this is the so-called a-helix), or folded into a folded layer (p-layer). Such a-helices and p-sheets are secondary structure. It occurs as a result of the formation of hydrogen bonds within one polypeptide chain (helical configuration) or between two polypeptide chains (folded layers).

Keratin protein has a completely a-helical configuration. It is the structural protein of hair, nails, claws, beaks, feathers and horns; it is part of the outer layer of vertebrate skin.

In most proteins, the helical and non-helical sections of the polypeptide chain fold into a three-dimensional spherical formation - a globule (characteristic of globular proteins). A globule of a certain configuration is tertiary structure squirrel. This structure is stabilized by ionic, hydrogen, covalent disulfide bonds (formed between sulfur atoms that are part of cysteine, cystine and megionine), as well as hydrophobic interactions. The most important in the emergence of tertiary structure are hydrophobic interactions; In this case, the protein folds in such a way that its hydrophobic side chains are hidden inside the molecule, i.e., they are protected from contact with water, and the hydrophilic side chains, on the contrary, are exposed outside.

Many proteins with a particularly complex structure consist of several polypeptide chains (subunits), forming quaternary structure protein molecule. This structure is found, for example, in the globular protein hemoglobin. Its molecule consists of four separate polypeptide subunits (protomers), located in the tertiary structure, and a non-protein part - heme.

Only in this structure is hemoglobin able to perform its transport function.

Under the influence of various chemical and physical factors (treatment with alcohol, acetone, acids, alkalis, high temperature, irradiation, high pressure, etc.), a change occurs in the secondary, tertiary and quaternary structures of the protein due to the rupture of hydrogen and ionic bonds. The process of disrupting the native (natural) structure of a protein is called denaturation. In this case, there is a decrease in protein solubility, a change in the shape and size of molecules, loss of enzymatic activity, etc. The denaturation process can be complete or partial. In some cases, the transition to normal environmental conditions is accompanied by spontaneous restoration of the natural structure of the protein. This process is called renaturation.

Simple and complex proteins. Based on their chemical composition, proteins are divided into simple and complex. Forgive me include proteins consisting only of amino acids, and difficult- proteins containing a protein part and a non-protein part (prosthetic); a prosthetic group can be formed by metal ions, a phosphoric acid residue, carbohydrates, lipids, etc. Simple proteins are serum albumin, fibrin, some enzymes (trypsin), etc. Complex proteins include all proteolipids and glycoproteins; complex proteins are, for example, immunoglobulins (antibodies), hemoglobin, most enzymes, etc.

Functions of proteins.

Structural. Proteins are part of cell membranes and the matrix of cell organelles. The walls of blood vessels, cartilage, tendons, hair, nails, and claws in higher animals consist primarily of proteins.
Catalytic (enzymatic). Enzyme proteins catalyze all chemical reactions in the body. They ensure the breakdown of nutrients in the digestive tract, carbon fixation during photosynthesis, etc.
Transport. Some proteins are capable of attaching and transporting various substances. Blood albumins transport fatty acids, globulins transport metal ions and hormones, and hemoglobin transports oxygen and carbon dioxide. Protein molecules that make up the plasma membrane take part in the transport of substances into the cell.
Protective. It is performed by immunoglobulins (antibodies) in the blood, which provide the body’s immune defense. Fibrinogen and thrombin are involved in blood clotting and prevent bleeding.
Contractile. Due to the sliding of actin and myosin protofibrils relative to each other, muscle contraction occurs, as well as non-muscle intracellular contractions. The movement of cilia and flagella is associated with the sliding of microtubules of a protein nature relative to each other.
Regulatory. Many hormones are oligopeptides or peptides (eg, insulin, glucagon [insulin antagonist], adrenocorticotropic hormone, etc.).
Receptor. Some proteins embedded in the cell membrane are able to change their structure under the influence of the external environment. This is how signals are received from the outside and information is transmitted into the cell. An example would be phyto-chrome—- a light-sensitive protein that regulates the photoperiodic response of plants, and opsin - component rhodopsin, pigment found in the cells of the retina.
Energy. Proteins can serve as a source of energy in the cell (after their hydrolysis). Typically, proteins are used for energy needs in extreme cases, when reserves of carbohydrates and fats are exhausted.

Enzymes (enzymes). These are specific proteins that are present in all living organisms and play the role of biological catalysts.

Chemical reactions in a living cell occur at a certain temperature, normal pressure and appropriate acidity of the environment. Under such conditions, reactions of synthesis or breakdown of substances would proceed very slowly in the cell if they were not exposed to enzymes. Enzymes speed up a reaction without changing its overall result by reducing activation energy, that is, when they are present, significantly less energy is required to make the molecules that react reactive, or the reaction proceeds along a different path with a lower energy barrier.

All processes in a living organism are carried out directly or indirectly with the participation of enzymes. For example, under their influence, the constituent components of food (proteins, carbohydrates, lipids, etc.) are broken down into simpler compounds, and from them new macromolecules characteristic of this type are then synthesized. Therefore, disturbances in the formation and activity of enzymes often lead to the occurrence of serious diseases.

According to their spatial organization, enzymes consist of several sexes and peptide chains and usually have a quaternary structure. In addition, enzymes can also include non-protein structures. The protein part is name apoenzyme, and non-protein - cofactor(if these are cations or anions of inorganic substances, for example, Zn 2- Mn 2+, etc.) or coenzyme (coenzyme)(if it is a low molecular weight organic substance).

Vitamins are precursors or components of many coenzymes. Thus, pantothenic acid is a component of coenzyme A, nicotinic acid (vitamin PP) is a precursor of NAD and NADP, etc.

Enzymatic catalysis obeys the same laws as non-enzymatic catalysis in the chemical industry, but unlike it it is characterized by unusual high degree of specificity(an enzyme catalyzes only one reaction or acts on only one type of bond). This ensures fine regulation of all vital processes (respiration, digestion, photosynthesis, etc.) occurring in the cell and body. For example, the enzyme urease catalyzes the breakdown of only one substance - urea (H 2 N-CO-NH 2 + H 2 O -> -» 2NH 3 + CO 2), without exerting a catalytic effect on structurally related compounds.

To understand the mechanism of action of enzymes with high specificity, it is very The theory of the active center is important. According to her, V molecule everyone enzyme there are one a site or more in which catalysis occurs due to close (at many points) contact between the molecules of the enzyme and a specific substance (substrate). The active center is either a functional group (for example, the OH group of serine) or a separate amino acid. Typically, a catalytic effect requires a combination of several (on average from 3 to 12) amino acid residues located in a certain order. The active center is also formed by metal ions, vitamins and other non-protein compounds associated with the enzyme - coenzymes, or cofactors. Moreover, the shape and chemical structure of the active center are such that With Only certain substrates can bind to it due to their ideal correspondence (complementarity or complementarity) to each other. The role of the remaining amino acid residues in a large enzyme molecule is to provide its molecule with the appropriate globular shape, which is necessary for the effective operation of the active center. In addition, a strong electric field arises around a large enzyme molecule. In such a field, it becomes possible for the substrate molecules to be oriented and acquire an asymmetric shape. This leads to a weakening of chemical bonds, and the catalyzed reaction occurs with less initial energy expenditure, and therefore at a much higher rate. For example, one molecule of the catalase enzyme can break down in 1 minute more than 5 million molecules of hydrogen peroxide (H 2 0 2), which arises during the oxidation of various compounds in the body.

In some enzymes, in the presence of a substrate, the configuration of the active center undergoes changes, i.e., the enzyme orients its functional groups in such a way as to ensure the greatest catalytic activity.

At the final stage of the chemical reaction, the enzyme-substrate complex is separated to form the final products and free enzyme. The active center released in this case can accept new substrate molecules.

Rate of enzymatic reactions depends on many factors: the nature and concentration of the enzyme and substrate, temperature, pressure, acidity of the medium, the presence of inhibitors, etc. For example, at temperatures close to zero, the rate of biochemical reactions slows down to a minimum. This property is widely used in various sectors of the national economy, especially in agriculture and medicine. In particular, conservation Before transplantation of various organs (kidneys, heart, spleen, liver) to a patient, they are cooled in order to reduce the intensity of biochemical reactions and prolong the life of the organs. Rapid freezing of food products prevents the growth and reproduction of microorganisms (bacteria, fungi, etc.), and also inactivates their digestive enzymes, so that they are no longer able to cause decomposition of food products.

Source : ON THE. Lemeza L.V. Kamlyuk N.D. Lisov "A manual on biology for those entering universities"

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CHAPTER 1. INTRODUCTION

Reports about a revolution in biology have now become quite banal. It is also indisputable that these revolutionary changes were associated with the formation of a complex of sciences at the intersection of biology and chemistry, among which molecular biology and bioorganic chemistry occupied and still occupy a central position.

“Molecular biology is a science that aims to understand the nature of life phenomena by studying biological objects and systems at a level approaching the molecular... characteristic manifestations of life... are determined by the structure, properties and interaction of molecules of biologically important substances, primarily proteins and nucleic acids ”

“Bioorganic chemistry is a science that studies the substances underlying life processes... the main objects of bioorganic chemistry are biopolymers (proteins and peptides, nucleic acids and nucleotides, lipids, polysaccharides, etc.).

From this comparison it becomes obvious how important the study of proteins is for the development of modern biology.

biology protein biochemistry

CHAPTER 2. HISTORY OF PROTEIN RESEARCH

2.1 Initial stages in protein chemistry

Protein became an object of chemical research 250 years ago. In 1728, the Italian scientist Jacopo Bartolomeo Beccari obtained the first protein preparation - gluten - from wheat flour. He subjected gluten to dry distillation and became convinced that the products of such distillation were alkaline. This was the first proof of the unity of nature of the substances of the plant and animal kingdoms. He published the results of his work in 1745, and it was the first paper on the protein.

In the 18th - early 19th centuries, protein substances of plant and animal origin were repeatedly described. The peculiarity of such descriptions was the convergence of these substances and their comparison with inorganic substances.

It is important to note that at this time, even before the advent of elemental analysis, the idea had developed that proteins from various sources were a group of individual substances with similar general properties.

In 1810, J. Gay-Lussac and L. Thénard first determined the elemental composition of protein substances. In 1833, J. Gay-Lussac proved that proteins necessarily contain nitrogen, and it was soon shown that the nitrogen content in different proteins is approximately the same. At the same time, the English chemist D. Dalton tried to depict the first formulas of protein substances. He imagined them as fairly simply structured substances, but in order to emphasize their individual differences with the same composition, he resorted to depicting molecules that would now be called isomeric. However, the concept of isomerism did not yet exist in Dalton's time.

D. Dalton's protein formulas

The first empirical formulas of proteins were derived and the first hypotheses were put forward regarding the patterns of their composition. Thus, N. Liberkühn believed that albumin is described by the formula C 72 H 112 N 18 SO 22, and A. Danilevsky believed that the molecule of this protein is at least an order of magnitude larger: C 726 H 1171 N 194 S 3 O 214.

The German chemist J. Liebig suggested in 1841 that proteins of animal origin have analogues among plant proteins: the absorption of legumin protein in the animal’s body, according to Liebig, led to the accumulation of a similar protein - casein. One of the most widespread theories of prestructural organic chemistry was the theory of radicals - unchanged components of related substances. In 1836, the Dutchman G. Mulder suggested that all proteins contain the same radical, which he called protein (from the Greek word “first”, “taking first place”). The protein, according to Mulder, had the composition Pr = C 40 H 62 N 10 O 12. In 1838, G. Mulder published protein formulas based on the protein theory. These were the so-called dualistic formulas, where the protein radical served as a positive group, and the sulfur or phosphorus atoms served as a negative group. Together they formed an electrically neutral molecule: serum protein Pr 10 S 2 P, fibrin Pr 10 SP. However, an analytical check of G. Mulder’s data, carried out by the Russian chemist Lyaskovsky, as well as J. Liebig, showed that “protein radicals” do not exist.

In 1833, the German scientist F. Rose discovered the biuret reaction to proteins - one of the main color reactions to protein substances and their derivatives at the present time (more about color reactions on p. 53). It was also concluded that this was the most sensitive reaction to protein, which is why it received the most attention from chemists at the time.

In the mid-19th century, numerous methods were developed for protein extraction, purification and isolation in solutions of neutral salts. In 1847, K. Reichert discovered the ability of proteins to form crystals. In 1836, T. Schwann discovered pepsin, an enzyme that breaks down proteins. In 1856, L. Corvisart discovered another similar enzyme - trypsin. By studying the action of these enzymes on proteins, biochemists tried to unravel the mystery of digestion. However, the greatest attention was attracted by substances resulting from the action of protelytic enzymes (proteases, these include the above enzymes) on proteins: some of them were fragments of the original protein molecules (they were called peptones ), others were not subjected to further cleavage by proteases and belonged to a class of compounds known since the beginning of the century - amino acids (the first amino acid derivative - asparagine amide was discovered in 1806, and the first amino acid - cystine in 1810). Amino acids in proteins were first discovered in 1820 by the French chemist A. Braconneau. He used acid hydrolysis of protein and discovered a sweetish substance in the hydrolyzate, which he called glycine. In 1839, the existence of leucine in proteins was proven, and in 1849, F. Bopp isolated another amino acid from protein - tyrosine (for a complete list of dates of discoveries of amino acids in proteins, see Appendix II).

By the end of the 80s. In the 19th century, 19 amino acids had already been isolated from protein hydrolysates, and the opinion slowly began to strengthen that information about the products of protein hydrolysis carried important information about the structure of the protein molecule. However, amino acids were considered an essential but non-essential component of protein.

In connection with the discoveries of amino acids in proteins, the French scientist P. Schutzenberger in the 70s. XIX century proposed the so-called. ureide theory protein structure. According to it, the protein molecule consisted of a central core, the role of which was played by a tyrosine molecule, and complex groups called Schutzenberger attached to it (with the replacement of 4 hydrogen atoms). leucines . However, the hypothesis was very weakly supported experimentally, and further research showed it to be untenable.

2.2 Theory of “carbon-nitrogen complexes” A.Ya. Danilevsky

The original theory about the structure of protein was expressed in the 80s. 19th century Russian biochemist A. Ya. Danilevsky. He was the first chemist to draw attention to the possible polymeric nature of the structure of protein molecules. In the early 70s. he wrote to A.M. Butlerov that “albumin particles are a mixed polymeride”, that to define protein he does not find “a term more suitable than the word polymer in the broad sense.” While studying the biuret reaction, he suggested that this reaction is associated with the structure of alternating carbon and nitrogen atoms - N - C - N - C - N -, which are included in the so-called. carbon dioxide T complex R" - NH - CO - NH - CO - R". Based on this formula, Danilevsky believed that the protein molecule contains 40 such carbon-nitrogen complexes. Individual carbon-nitrogen amino acid complexes, according to Danilevsky, looked like this:

According to Danilevsky, carbon-nitrogen complexes could be connected by an ether or amide bond to form a high-molecular structure.

2.3 Theory of “Kirins” A. Kossel

The German physiologist and biochemist A. Kossel, studying protamines and histones, relatively simply structured proteins, found that their hydrolysis produces a large amount of arginine. In addition, he discovered a then unknown amino acid in the hydrolyzate - histidine. Based on this, Kossel suggested that these protein substances can be considered as some simple models of more complex proteins, built, in his opinion, according to the following principle: arginine and histidine form a central core (“protamine core”), which is surrounded by complexes of other amino acids.

Kossel's theory was the most perfect example of the development of the hypothesis about the fragmentary structure of proteins (first proposed, as mentioned above, by G. Mulder). This hypothesis was used by the German chemist M. Siegfried at the beginning of the 20th century. He believed that proteins were built from complexes of amino acids (arginine + lysine + glutamine acid), which he named kirins (from the Greek “kyrios” main). However, this hypothesis was expressed in 1903, when E. Fischer was actively developing his peptide theory , which gave the key to the secret of the structure of proteins.

2.4 Peptide theory E. Fisher

The German chemist Emil Fischer, already famous throughout the world for his studies of purine compounds (alkaloids of the caffeine group) and deciphering the structure of sugars, created a peptide theory, which was largely confirmed in practice and received universal recognition during his lifetime, for which he was awarded the second Nobel Prize in the history of chemistry prize (the first was received by J.G. Van't Hoff).

It is important that Fisher constructed a research plan that was sharply different from what had been undertaken before, but took into account all the facts known at that time. First of all, he accepted as the most probable hypothesis that proteins are built from amino acids connected by an amide bond:

Fisher called this type of bond (by analogy with peptones) peptide . He suggested that proteins are polymers of amino acids linked by peptide bonds . The idea of the polymeric nature of the structure of proteins, as is known, was expressed by Danilevsky and Hurt, but they believed that “monomers” were very complex formations - peptones or “carbon-nitrogen complexes”.

Proving the peptide type of connection of amino acid residues. E. Fischer proceeded from the following observations. Firstly, both during the hydrolysis of proteins and during their enzymatic decomposition, various amino acids were formed. Other compounds were extremely difficult to describe and even more difficult to obtain. In addition, Fischer knew that proteins do not have a predominance of either acidic or basic properties, which means, he reasoned, the amino and carboxyl groups in the composition of amino acids in protein molecules are closed and, as it were, mask each other (amphotericity of proteins, as they would say now ).

Fischer divided the solution to the problem of protein structure, reducing it to the following provisions:

Qualitative and quantitative determination of products of complete protein hydrolysis.

Establishment of the structure of these final products.

Synthesis of amino acid polymers with amide (peptide) type compounds.

Comparison of compounds obtained in this way with natural proteins.

From this plan it is clear that Fischer was the first to use a new methodological approach - the synthesis of model compounds as a method of proof by analogy.

2.5 Development of methods for amino acid synthesis

In order to move on to the synthesis of amino acid derivatives connected by peptide bonds, Fischer did a lot of work on studying the structure and synthesis of amino acids.

Before Fischer, the general method for the synthesis of amino acids was the cyanohydrin synthesis by A. Strecker:

Using the Strecker reaction, it was possible to synthesize alanine, serine and some other amino acids, and by its modification (Zelinsky-Stadnikov reaction) both -amino acids and their N-substituted ones.

However, Fischer himself sought to develop methods for the synthesis of all then known amino acids. He considered Strecker's method not universal enough. Therefore, E. Fischer had to look for a general method for the synthesis of amino acids, including amino acids with complex side radicals.

He proposed the amination of bromo-substituted carboxylic acids in the -position. To obtain bromo derivatives, he used, for example, in the synthesis of leucine, arylated or alkylated malonic acid:

But E. Fischer failed to create an absolutely universal method. More reliable reactions have also been developed. For example, Fischer's student G. Lakes proposed the following modification to obtain serine:

Fischer also proved that proteins consist of optically active amino acid residues (see p. 11). This forced him to develop a new nomenclature of optically active compounds, methods for the separation and synthesis of optical isomers of amino acids. Fischer also came to the conclusion that proteins contain residues of L-forms of optically active amino acids, and he proved this by first using the principle of diastereoisomerism. This principle was as follows: an optically active alkaloid (brucine, strychnine, cinchonine, quinidine, quinine) was added to the N-acyl derivative of a racemic amino acid. As a result, two stereoisomeric forms of salts with different solubilities were formed. After separation of these diastereoisomers, the alkaloid was regenerated and the acyl group was removed by hydrolysis.

Fischer was able to develop a method for the complete determination of amino acids in the products of protein hydrolysis: he converted hydrochlorides of amino acid esters by treatment with concentrated alkali in the cold into free esters, which were not noticeably saponified. Then the mixture of these esters was subjected to fractional distillation and individual amino acids were isolated from the resulting fractions by fractional crystallization.

The new analysis method not only finally confirmed that proteins consist of amino acid residues, but also made it possible to clarify and expand the list of amino acids found in proteins. But still, quantitative analyzes could not answer the main question: what are the principles of the structure of the protein molecule. And E. Fisher formulated one of the main tasks in the study of the structure and properties of proteins: development experimental memethods for the synthesis of compounds whose main components would be amino acidsOyou, connected by a peptide bond.

Thus, Fischer set a non-trivial task - to synthesize a new class of compounds in order to establish the principles of their structure.

Fisher solved this problem, and chemists received convincing evidence that proteins are polymers of amino acids connected by a peptide bond:

CO - CHR" - NH - CO - CHR"" - NH - CO CHR""" - NH -

This position was confirmed by biochemical evidence. Along the way, it turned out that proteases do not hydrolyze all bonds between amino acids at the same rate. Their ability to cleave the peptide bond was influenced by the optical configuration of amino acids, nitrogen substituents of the amino group, the length of the peptide chain, as well as the set of residues included in it.

The main proof of the peptide theory was the synthesis of model peptides and their comparison with peptones of protein hydrolysates. The results showed that peptides identical to those synthesized were isolated from protein hydrolysates.

In the process of carrying out these studies, E. Fisher and his student E. Abdergalden first developed a method for determining the amino acid sequence of a protein. Its essence was to establish the nature of the amino acid residue of a polypeptide having a free amino group (N-terminal amino acid). To do this, they proposed blocking the amino terminus of the peptide with a naphthalene sulfonyl group, which is not cleaved off during hydrolysis. By then isolating the amino acid labeled with such a group from the hydrolyzate, it was possible to determine which of the amino acids was N-terminal.

After E. Fisher's research, it became clear that proteins are polypeptides. This was an important achievement, including for the tasks of protein synthesis: it became clear what exactly needed to be synthesized. Only after these works the problem of protein synthesis acquired a certain focus and the necessary rigor.

Speaking about Fischer’s work as a whole, it should be noted that the approach to the research itself was more typical for the coming 20th century - it operated with a wide range of theoretical positions and methodological techniques; his syntheses looked less and less like an art based on intuition rather than on precise knowledge, and came closer to creating a series of precise, almost technological techniques.

2. 6 The crisis of the peptide theory

In connection with the use of new physical and physicochemical research methods in the early 20s. XX century doubts arose that the protein molecule represents a long polypeptide chain. The hypothesis about the possibility of compact folding of peptide chains was treated with skepticism. All this required a revision of E. Fisher's peptide theory.

In the 20-30s. The diketopiperazine theory became widespread. According to it, the central role in the construction of protein structure is played by diketopiperase rings formed during the cyclization of two amino acid residues. It was also assumed that these structures constitute the central core of the molecule, to which short peptides or amino acids are attached (“fillers” of the cyclic skeleton of the main structure). The most convincing schemes for the participation of diketopiperazines in the construction of protein structure were presented by N.D. Zelinsky and E. Fisher’s students.

However, attempts to synthesize model compounds containing diketopiperazines yielded little for protein chemistry; the peptide theory subsequently triumphed, but these works had a stimulating effect on the chemistry of piperazines in general.

After the peptide and diketopiperase theories, attempts continued to prove the existence of only peptide structures in the protein molecule. At the same time, they tried to imagine not only the type of molecule, but also its general outline.

The original hypothesis was expressed by the Soviet chemist D.L. Talmud. He suggested that the peptide chains within protein molecules are folded into large rings, which in turn was a step towards his creation of the idea of a protein globule.

At the same time, data appeared indicating a different set of amino acids in different proteins. But the patterns governing the sequence of amino acids in the protein structure were not clear.

M. Bergman and K. Niemann were the first to try to answer this question in the hypothesis of “intermittent frequencies” they developed. According to it, the sequence of amino acid residues in a protein molecule was subject to numerical patterns, the foundations of which were derived from the principles of the structure of the protein molecule of silk fibroin. But this choice was unsuccessful, because... this protein is fibrillar, while the structure of globular proteins obeys completely different laws.

According to M. Bergman and K. Niemann, each amino acid occurs in the polypeptide chain at a certain interval or, as M. Bergman said, has a certain “periodicity.” This periodicity is determined by the nature of the amino acid residues.

They imagined the silk fibroin molecule as follows:

GlyAlaGlyTyr GlyAlaGlyArg GlyAlaGlyx GlyAlaGlyx

(GlyAlaGlyTyr GlyAlaGlyx GlyAlaGlyx GlyAlaGlyx) 12

GlyAlaGlyTyr GlyAlaGlyx GlyAlaGlyx GlyAlaGlyArg

(GlyAlaGlyTyr GlyAlaGlyx GlyAlaGlyx GlyAlaGlyx) 13

The Bergmann-Niemann hypothesis had a significant impact on the development of amino acid chemistry; a large number of works were devoted to its verification.

In conclusion of this chapter, it should be noted that by the middle of the 20th century. sufficient evidence of the validity of the peptide theory has been accumulated, its main provisions have been supplemented and clarified. Therefore, the center for protein research in the 20th century. lay already in the field of research and search for methods of synthesizing protein artificially. This problem was successfully solved; reliable methods were developed for determining the primary structure of a protein - the sequence of amino acids in the peptide chain; methods for the chemical (abiogenic) synthesis of irregular polypeptides were developed (these methods are discussed in more detail in Chapter 8, p. 36), including methods for automatic synthesis of polypeptides. This allowed already in 1962 the leading English chemist F. Sanger to decipher the structure and artificially synthesize the hormone insulin, which marked a new era in the synthesis of polypeptides of functional proteins.

CHAPTER 3. CHEMICAL COMPOSITION OF PROTEINS

3.1 Peptide bond

Proteins are irregular polymers built from amino acid residues, the general formula of which in an aqueous solution at pH values close to neutral can be written as NH 3 + CHRCOO - . Amino acid residues in proteins are connected by an amide bond between the -amino and -carboxyl groups. Peptide bond between two-amino acid residues are usually called peptide bond , and polymers built from amino acid residues connected by peptide bonds are called polypeptides. A protein, as a biologically significant structure, can be either one polypeptide or several polypeptides that form a single complex as a result of non-covalent interactions.

3.2 Elemental composition of proteins

When studying the chemical composition of proteins, it is necessary to find out, firstly, what chemical elements they consist of, and secondly, the structure of their monomers. To answer the first question, the quantitative and qualitative composition of the chemical elements of the protein is determined. Chemical analysis showed present in all proteins carbon (50-55%), oxygen (21-23%), nitrogen (15-17%), hydrogen (6-7%), sulfur (0.3-2.5%). Phosphorus, iodine, iron, copper and some other macro- and microelements, in various, often very small quantities, were also found in the composition of individual proteins.

The content of basic chemical elements in proteins may vary, with the exception of nitrogen, the concentration of which is characterized by the greatest constancy and averages 16%. In addition, the nitrogen content of other organic matter is low. In accordance with this, it was proposed to determine the amount of protein by the nitrogen contained in it. Knowing that 1 g of nitrogen is contained in 6.25 g of protein, the found amount of nitrogen is multiplied by a factor of 6.25 and the amount of protein is obtained.

To determine the chemical nature of protein monomers, it is necessary to solve two problems: divide the protein into monomers and find out their chemical composition. The breakdown of protein into its component parts is achieved using hydrolysis - prolonged boiling of the protein with strong mineral acids (acid hydrolysis) or reasons (alkaline hydrolysis). The most commonly used method is boiling at 110 C with HCl for 24 hours. At the next stage, the substances included in the hydrolyzate are separated. For this purpose, various methods are used, most often chromatography (for more details, see the chapter “Research Methods...”). The main part of the separated hydrolysates are amino acids.

3.3. Amino acids

Currently, up to 200 different amino acids have been found in various objects of living nature. In the human body, for example, there are about 60 of them. However, proteins contain only 20 amino acids, sometimes called natural ones.

Amino acids are organic acids in which the hydrogen atom of the carbon atom is replaced by an amino group - NH 2. Therefore, by chemical nature these are amino acids with the general formula:

From this formula it is clear that all amino acids include the following general groups: - CH 2, - NH 2, - COOH. Side chains (radicals - R) amino acids differ. As can be seen from Appendix I, the chemical nature of radicals is diverse: from the hydrogen atom to cyclic compounds. It is radicals that determine the structural and functional characteristics of amino acids.

All amino acids, except for the simplest aminoacetic acid glycine (NH 3 + CH 2 COO) have a chiral C atom and can exist in the form of two enantiomers (optical isomers):

All currently studied proteins contain only L-series amino acids, in which, if we consider the chiral atom from the side of the H atom, the NH 3 +, COO and radical R groups are located clockwise. When constructing a biologically significant polymer molecule, the need to build it from a strictly defined enantiomer is obvious - from a racemic mixture of two enantiomers an unimaginably complex mixture of diastereoisomers would be obtained. The question of why life on Earth is based on proteins built specifically from L- rather than D-amino acids still remains an intriguing mystery. It should be noted that D-amino acids are quite widespread in living nature and, moreover, are part of biologically significant oligopeptides.

Proteins are built from twenty basic amino acids, but the rest, quite diverse amino acids, are formed from these 20 amino acid residues already in the protein molecule. Among such transformations, we should first of all note the formation disulfide bridges during the oxidation of two cysteine residues in already formed peptide chains. As a result, a diaminodicarboxylic acid residue is formed from two cysteine residues cystine (See Appendix I). In this case, cross-linking occurs either within one polypeptide chain or between two different chains. As a small protein having two polypeptide chains, connected by disulfide bridges, as well as cross-links within one of the polypeptide chains:

An important example of modification of amino acid residues is the conversion of proline residues into residues hydroxyproline :

This transformation occurs, and on a significant scale, with the formation of an important protein component of connective tissue - collagen .

Another very important type of protein modification is phosphorylation of hydroxyl groups of serine, threonine and tyrosine residues, for example:

Amino acids in an aqueous solution are in an ionized state due to the dissociation of amino and carboxyl groups that are part of the radicals. In other words, they are amphoteric compounds and can exist either as acids (proton donors) or bases (donor acceptors).

All amino acids, depending on their structure, are divided into several groups:

Acyclic. Monoaminomonocarboxylic amino acids They contain one amine and one carboxyl group; they are neutral in an aqueous solution. Some of them have common structural features, which allows us to consider them together:

Glycine and alanine. Glycine (glycocol or aminoacetic acid) is optically inactive - it is the only amino acid that does not have enantiomers. Glycine is involved in the formation of nucleic and bile acids, heme, and is necessary for the neutralization of toxic products in the liver. Alanine is used by the body in various processes of carbohydrate and energy metabolism. Its isomer, alanine, is a component of vitamin pantothenic acid, coenzyme A (CoA), and muscle extractives.

Serine and threonine. They belong to the group of hydroxy acids, because have a hydroxyl group. Serine is a component of various enzymes, the main protein of milk - casein, as well as many lipoproteins. Threonine is involved in protein biosynthesis, being an essential amino acid.

Cysteine and methionine. Amino acids containing a sulfur atom. The importance of cysteine is determined by the presence of a sulfhydryl (- SH) group in its composition, which gives it the ability to easily oxidize and protect the body from substances with high oxidative capacity (in case of radiation injury, phosphorus poisoning). Methionine is characterized by the presence of a readily mobile methyl group, which is used for the synthesis of important compounds in the body (choline, creatine, thymine, adrenaline, etc.)

Valine, leucine and isoleucine. They are branched amino acids that actively participate in metabolism and are not synthesized in the body.

Monoaminodicarboxylic amino acids have one amine and two carboxyl groups and give an acidic reaction in aqueous solution. These include aspartic and glutamic acids, asparagine and glutamine. They are part of the inhibitory mediators of the nervous system.

Diaminomonocarboxylic amino acids in an aqueous solution they have an alkaline reaction due to the presence of two amine groups. Lysine, which belongs to them, is necessary for the synthesis of histones and also in a number of enzymes. Arginine is involved in the synthesis of urea and creatine.

Cyclic. These amino acids have an aromatic or heterocyclic ring and, as a rule, are not synthesized in the human body and must be supplied with food. They actively participate in various metabolic processes. Thus, phenyl-alanine serves as the main source of the synthesis of tyrosine, a precursor to a number of biologically important substances: hormones (thyroxine, adrenaline), and some pigments. Tryptophan, in addition to participating in protein synthesis, serves as a component of vitamin PP, serotonin, tryptamine, and a number of pigments. Histidine is necessary for protein synthesis and is a precursor of histamine, which affects blood pressure and gastric juice secretion.

CHAPTER 4. STRUCTURE

When studying the composition of proteins, it was found that they are all built on a single principle and have four levels of organization: primary, secondary, tertiary, and some of them quaternary structures.

4.1 Primary structure

It is a linear chain of amino acids arranged in a specific sequence and connected by peptide bonds. Peptide bond is formed due to the -carboxyl group of one amino acid and the -amine group of another:

The peptide bond, due to the p, -conjugation - bond of the carbonyl group and the p-orbital of the N atom, which contains an unshared pair of electrons, cannot be considered as single and there is practically no rotation around it. For the same reason, the chiral atom C and the carbonyl atom C k of any i-th amino acid residue of the peptide chain and the N and C atoms of the (i+1)-th residue are in the same plane. In the same plane are the carbonyl atom O and the amide atom H (however, the material accumulated during the study of the structure of proteins shows that this statement is not entirely strict: the atoms associated with the peptide nitrogen atom are not in the same plane with it, but form a trihedral pyramid with angles between bonds very close to 120. Therefore, between the planes formed by the atoms C i, C i k, O i and N i +1, Hi +1, C i +1, there is some angle different from 0. But, as As a rule, it does not exceed 1 and does not play a special role). Therefore, geometrically, a polypeptide chain can be considered as formed by such flat fragments, each containing six atoms. The relative position of these fragments, like any relative position of two planes, must be determined by two angles. As such, it is customary to take torsion angles that characterize rotations around the N C and C C k -bonds.

The geometry of any molecule is determined by three groups of geometric characteristics of its chemical bonds - bond lengths, bond angles and torsion angles between bonds adjacent to neighboring atoms. The first two groups are decisively determined by the nature of the atoms involved and the bonds formed. Therefore, the spatial structure of polymers is mainly determined by the torsion angles between the links of the polymer backbone of the molecules, i.e. conformation of the polymer chain. That R sion angle , i.e. angle of rotation of the A-B bond around the B-C bond relative to the C- bondD, is defined as the angle between the planes containing atoms A, B, C and atomsB, C, D.

In such a system, it is possible that the A-B and C-D bonds are located in parallel and are located on one side of the B-C bond. If we consider this system along the St.Izi B-C, then the A-B connection seems to obscure the connectionC- D, therefore this conformation is calledsvariesobscured. According to the recommendations of the international chemistry unions IUPAC (International Union of Pure and Applied Chemistry) and IUB (International Union of Biochemistry), the angle between the ABC and BCD planes is considered positive if the conformation closest to the observer is brought to an eclipsed state by rotating through an angle of no more than 180 The connection must be turned clockwise. If this bond must be rotated counterclockwise to obtain the eclipsed conformation, then the angle is considered negative. It can be noted that this definition does not depend on which of the connections is closer to the observer.

In this case, as can be seen from the figure, the orientation of the fragment containing atoms C i -1 and C i [(i-1)-th fragment], and the fragment containing atoms C i and C i +1 (i-th fragment), is determined by torsion angles corresponding to rotation around the N i C i bond and the C i C i k bond. These angles are usually denoted as and, in the above case i and i respectively. Their values for all monomer units of a polypeptide chain mainly determine the geometry of this chain. There are no unambiguous values for either the value of each of these angles or their combinations, although restrictions are imposed on both of them, determined both by the properties of the peptide fragments themselves and by the nature of the side radicals, i.e. the nature of amino acid residues.

To date, amino acid sequences have been established for several thousand different proteins. Recording the structure of proteins in the form of detailed structural formulas is cumbersome and not clear. Therefore, an abbreviated form of notation is used - three-letter or one-letter (vasopressin molecule):

When writing the amino acid sequence in polypeptide or oligopeptide chains using abbreviated symbols, unless otherwise noted, it is assumed that the -amino group is on the left and the -carboxyl group is on the right. The corresponding sections of the polypeptide chain are called the N-terminus (amine end) and C-terminus (carboxyl end), and the amino acid residues are called N-terminal and C-terminal residues, respectively.

4.2 Secondary structure

Fragments of the spatial structure of a biopolymer, having a periodic structure of the polymer backbone, are considered as elements of the secondary structure.

If over a certain section of the chain the same type of angles discussed on page 15 are approximately the same, then the structure of the polypeptide chain becomes periodic. There are two classes of such structures - spiral and stretched (flat or folded).

Spiral a structure in which all atoms of the same type lie on the same helix is considered. In this case, the spiral is considered right-handed if, when observed along the axis of the spiral, it moves away from the observer clockwise, and left-handed if it moves away counterclockwise. A polypeptide chain has a helical conformation if all C atoms are on one helix, all C k carbonyl atoms are on another, all N atoms are on a third, and the helix pitch for all three groups of atoms must be the same. The number of atoms per turn of the spiral should be the same, regardless of whether we are talking about atoms C k, C or N. The distance to the common helix is different for each of these three types of atoms.

The main elements of the secondary structure of proteins are -helices and -folds.

Helical protein structures. Several different types of helices are known for polypeptide chains. Among them, the most common is the right-handed helix. An ideal -helix has a pitch of 0.54 nm and the number of atoms of the same type per turn of the helix is 3.6, which means complete periodicity over five turns of the helix every 18 amino acid residues. The values of torsion angles for an ideal -helix = - 57 = - 47, and the distances from the atoms forming the polypeptide chain to the helix axis are 0.15 nm for N, 0.23 nm for C, 0.17 nm for C k. Any conformation exists provided that there are factors that stabilize it. In the case of an -helix, such factors are the hydrogen bonds formed by each carbonyl atom of the (i+4) fragment. An important factor in the stabilization of the α-helix is also the parallel orientation of the dipole moments of the peptide bonds.

Folded protein structures. One common example of a folded periodic protein structure is the so-called. -folds, consisting of two fragments, each of which is represented by a polypeptide.

The folds are also stabilized by hydrogen bonds between the hydrogen atom of the amine group of one fragment and the oxygen atom of the carboxyl group of the other fragment. In this case, the fragments can have both parallel and antiparallel orientation relative to each other.

The structure resulting from such interactions is a corrugated structure. This affects the values of torsion angles and. If in a flat, fully stretched structure they should be 180, then in real -layers they have values = - 119 and = + 113. In order for two sections of the polypeptide chain to be located in an orientation favorable to the formation of -folds, there must be a an area that has a structure that is sharply different from the periodic one.

4.2.1 Factors influencing the formation of secondary structure

The structure of a particular section of a polypeptide chain significantly depends on the structure of the molecule as a whole. The factors influencing the formation of areas with a certain secondary structure are very diverse and are not completely identified in all cases. It is known that a number of amino acid residues preferentially occur in -helical fragments, a number of others - in -folds, and some amino acids - mainly in areas lacking a periodic structure. The secondary structure is largely determined by the primary structure. In some cases, the physical meaning of such a dependence can be understood from a stereochemical analysis of the spatial structure. For example, as can be seen from the figure in the -helix, not only the side radicals of amino acid residues adjacent along the chain are brought closer together, but also some pairs of residues located on adjacent turns of the helix, primarily each (i+1)th residue with (i+4) -th and with (i+5)th. Therefore, in positions (i+1) and (i+2), (i+1) and (i+4), (i+1) and (i+5) -helices, two bulky radicals rarely occur simultaneously, such as , as side radicals of tyrosine, tryptophan, isoleucine. The simultaneous presence of three bulky residues in positions (i+1), (i+2) and (i+5) or (i+1), (i+4) and (i+5) is even less compatible with the structure of the helix. Therefore, such combinations of amino acids in α-helical fragments are a rare exception.

4.3 Tertiary structure

This term refers to the complete spatial arrangement of the entire polypeptide chain, including the arrangement of side radicals. A complete picture of the tertiary structure is given by the coordinates of all atoms of the protein. Thanks to the enormous success of X-ray diffraction analysis, such data, with the exception of the coordinates of hydrogen atoms, have been obtained for a significant number of proteins. These are huge amounts of information stored in special data banks on machine-readable media, and their processing is unthinkable without the use of high-speed computers. The atomic coordinates obtained on computers provide complete information about the geometry of the polypeptide chain, including the values of torsion angles, which makes it possible to identify a helical structure, -folds or irregular fragments. An example of such a research approach is the following spatial model of the structure of the enzyme phosphoglycerate kinase:

General diagram of the structure of phosphoglycerate kinase. For clarity, the -helical regions are presented as cylinders, and the -folds are presented as ribbons with an arrow indicating the direction of the chain from the N-terminus to the C-terminus. Lines are irregular sections connecting structured fragments.

An image of the complete structure of even a small protein molecule on a plane, be it a book page or a display screen, is not very informative due to the extremely complex structure of the object. So that the researcher can visually represent the spatial structure of the molecules of complex substances, three-dimensional computer graphics methods are used, which make it possible to display individual parts of the molecules and manipulate them, in particular, rotate them in the desired angles.

The tertiary structure is formed as a result of non-covalent interactions (electrostatic, ionic, van der Waals forces, etc.) of side radicals framing -helices and -folds, and non-periodic fragments of the polypeptide chain. Among the bonds holding the tertiary structure, it should be noted:

a) disulfide bridge (- S - S -)

b) ester bridge (between the carboxyl group and the hydroxyl group)

c) salt bridge (between the carboxyl group and the amino group)

d) hydrogen bonds.

In accordance with the shape of the protein molecule, determined by the tertiary structure, the following groups of proteins are distinguished:

Globular proteins. The spatial structure of these proteins can be roughly represented as a sphere or a not too elongated ellipsoid - globatly. As a rule, a significant part of the polypeptide chain of such proteins forms -helices and -folds. The relationship between them can be very different. For example, at myoglobin(more about it on p. 28) there are 5 -spiral segments and not a single -fold. In immunoglobulins (more details on page 42), on the contrary, the main elements of the secondary structure are -folds, and -helices are completely absent. In the above structure of phosphoglycerate kinase, both types of structures are represented approximately equally. In some cases, as can be seen in the example of phosphoglycerate kinase, two or more parts clearly separated in space (but nevertheless, of course, connected by peptide bridges) are clearly visible - domains. Often, different functional regions of a protein are separated into different domains.

Fibrillar proteins. These proteins have an elongated thread-like shape; they perform a structural function in the body. In the primary structure, they have repeating regions and form a secondary structure that is fairly uniform for the entire polypeptide chain. Thus, the protein creatine (the main protein component of nails, hair, skin) is built from extended α-helices. Silk fibroin consists of periodically repeating fragments Gly - Ala - Gly - Ser, forming -folds. There are less common elements of secondary structure, for example, the polypeptide chains of collagen that form left-handed spirals with parameters that differ sharply from the parameters of -helices. In collagen fibers, three helical polypeptide chains are twisted into a single right-handed superhelix:

4.4 Quaternary structure

In most cases, for proteins to function, it is necessary for several polymer chains to be combined into a single complex. Such a complex is also considered as a protein consisting of several subunits. Subunit structure often appears in scientific literature as quaternary structure.

Proteins consisting of several subunits are widespread in nature. A classic example is the quaternary structure of hemoglobin (more details - p. 26). subunits are usually designated by Greek letters. Hemoglobin has two subunits. The presence of several subunits is functionally important - it increases the degree of oxygen saturation. The quaternary structure of hemoglobin is designated as 2 2.

The subunit structure is characteristic of many enzymes, primarily those that perform complex functions. For example, RNA polymerase from E. coli has a 2" subunit structure, i.e., it is built from four different types of subunits, and the -subunit is duplicated. This protein performs complex and diverse functions - it initiates DNA, binds substrates - ribonucleoside triphosphates, and also transfers nucleotide residues to the growing polyribonucleotide chain and some other functions .

The work of many proteins is subject to the so-called. allosteric regulation- special compounds (effectors) “turn off” or “turn on” the work of the active center of the enzyme. Such enzymes have special effector recognition regions. And there are even special regulatory subunits, which also includes the indicated areas. A classic example is protein kinase enzymes, which catalyze the transfer of a phosphorus residue from an ATP molecule to substrate proteins.

CHAPTER 5. PROPERTIES

Proteins have a high molecular weight, some are soluble in water, are capable of swelling, and are characterized by optical activity, mobility in an electric field, and some other properties.

Proteins are high molecular weight compounds. These are polymers consisting of hundreds and thousands of amino acid residues - monomers. Accordingly molecular mass proteins is in the range of 10,000 - 1,000,000. Thus, ribonuclease (an enzyme that breaks down RNA) contains 124 amino acid residues and its molecular weight is approximately 14,000. Myoglobin (muscle protein), consisting of 153 amino acid residues, has a molecular weight 17,000, and hemoglobin - 64,500 (574 amino acid residues). The molecular weights of other proteins are higher: -globulin (forms antibodies) consists of 1250 amino acids and has a molecular weight of about 150,000, and the molecular weight of the enzyme glutamate dehydrogenase exceeds 1,000,000.

Determination of molecular weight is carried out by various methods: osmometric, gel filtration, optical, etc. however, the most accurate is the sedimentation method proposed by T. Svedberg. It is based on the fact that during ultracentrifugation with acceleration up to 900,000 g, the sedimentation rate of proteins depends on their molecular weight.

The most important property of proteins is their ability to exhibit both acidic and basic properties, that is, to act as amphoteric electrolytes. This is ensured by various dissociating groups that are part of amino acid radicals. For example, the acidic properties of protein are imparted by the carboxyl groups of aspartic glutamic amino acids, and the alkaline ones are imparted by the radicals of arginine, lysine and histidine. The more dicarboxylic amino acids a protein contains, the more pronounced its acidic properties and vice versa.

These same groups also have electrical charges that form the overall charge of the protein molecule. In proteins where aspartic and glutamine amino acids predominate, the protein charge will be negative; an excess of basic amino acids gives a positive charge to the protein molecule. As a result, in an electric field, proteins will move towards the cathode or anode, depending on the magnitude of their total charge. Thus, in an alkaline environment (pH 7 - 14) the protein donates a proton and becomes negatively charged, while in an acidic environment (pH 1 - 7) the dissociation of acid groups is suppressed and the protein becomes a cation.

Thus, the factor determining the behavior of a protein as a cation or anion is the reaction of the environment, which is determined by the concentration of hydrogen ions and is expressed by the pH value. However, at certain pH values, the number of positive and negative charges is equalized and the molecule becomes electrically neutral, i.e. it will not move in an electric field. This pH value of the medium is defined as the isoelectric point of proteins. In this case, the protein is in the least stable state and with minor changes in pH to the acidic or alkaline side it easily precipitates. For most natural proteins, the isoelectric point is in a slightly acidic environment (pH 4.8 - 5.4), which indicates the predominance of dicarboxylic amino acids in their composition.

The property of amphotericity underlies the buffering properties of proteins and their participation in the regulation of blood pH. The pH value of human blood is constant and ranges from 7.36 to 7.4, despite various substances of an acidic or basic nature that are regularly supplied with food or formed in metabolic processes - therefore, there are special mechanisms for regulating the acid-base balance of the internal environment of the body. Such systems include the one discussed in Chapter. “Classification” hemoglobin buffer system (p. 28). A change in blood pH by more than 0.07 indicates the development of a pathological process. A pH shift to the acidic side is called acidosis, and to the alkaline side - alkalosis.

Of great importance for the body is the ability of proteins to adsorb on their surface certain substances and ions (hormones, vitamins, iron, copper), which are either poorly soluble in water or are toxic (bilirubin, free fatty acids). Proteins transport them through the blood to places of further transformation or neutralization.

Aqueous solutions of proteins have their own characteristics. Firstly, proteins have a high affinity for water, i.e. They hydrophilic. This means that protein molecules, like charged particles, attract water dipoles, which are located around the protein molecule and form a water or hydration shell. This shell protects the protein molecules from sticking together and precipitating. The size of the hydration shell depends on the structure of the protein. For example, albumins bind water more easily and have a relatively large water shell, while globulins and fibrinogen bind water less well, and the hydration shell is smaller. Thus, the stability of an aqueous protein solution is determined by two factors: the presence of a charge on the protein molecule and the aqueous shell around it. When these factors are removed, the protein precipitates. This process can be reversible or irreversible.

...

Proteins: starting with theory

As has been mentioned several times in previous materials, food enters the human body in the form of nutrients: proteins, fats, carbohydrates, vitamins, minerals. But information has never been mentioned about how much certain substances need to be consumed in order to achieve certain goals. Today we will talk about this too.

If we talk about the definition of protein, then the simplest and most understandable statement will be Engels’s statement that the existence of protein bodies is life. Here it immediately becomes clear: no protein - no life. If we consider this definition in terms of bodybuilding, then without protein there will be no sculpted muscles. Now it's time to dive a little into the science.

Protein (protein) is a high-molecular organic substance that consists of alpha acids. These tiny particles are connected into a single chain by peptide bonds. Protein contains 20 types of amino acids (9 of them are essential, that is, they are not synthesized in the body, and the remaining 11 are replaceable).

The irreplaceable ones include:

Leucine;
Valin;
Isoleucine;
Licin;
Tryptophan;
Histidine;
Threonine;
Methionine;
Phenylalanine.

Replaceable items include:

Alanine;
Serin;
Cystine;
Argenine;
Tyrosine;
Proline;
Glycine;
Asparagine;
Glutamine;
Aspartic and glutamic acids.

In addition to these amino acids included in the composition, there are others that are not included in the composition, but play an important role. For example, gamma-aminobutyric acid is involved in the transmission of nerve impulses in the nervous system. dioxyphenylalanine has the same function. Without these substances, the workout would turn into something incomprehensible, and the movements would be similar to the random jerks of an amoeba.

The most important amino acids for the body (if we consider it in terms of metabolism) are:

Isoleucine;

These amino acids are also known as BCAA.

Each of the three amino acids plays an important role in processes associated with the energy components of muscle function. And for these processes to take place as correctly and efficiently as possible, each of them (amino acids) must be part of the daily diet (together with natural food or as supplements). To get specific data on how much you need to consume important amino acids, check out the table:

All proteins contain elements such as:

Carbon;
Hydrogen;
Sulfur;
Oxygen;
Nitrogen;
Phosphorus.

In view of this, it is very important not to forget about such a concept as nitrogen balance. The human body can be called a kind of nitrogen processing station. And all because nitrogen not only enters the body along with food, but is also released from it (during the breakdown of proteins).

The difference between the amount of nitrogen consumed and released is the nitrogen balance. It can be either positive (when more is consumed than excreted) or negative (vice versa). And if you want to gain muscle mass and build beautiful, sculpted muscles, this will only be possible under conditions of a positive nitrogen balance.

Important:

Depending on how trained the athlete is, different amounts of nitrogen may be needed to maintain the required level of nitrogen balance (per 1 kg of body weight). The average numbers are:

An athlete with existing experience (about 2-3 years) - 2g per 1kg of body weight;
Beginner athlete (up to 1 year) - 2 or 3 g per 1 kg of body weight.

But protein is not only a structural element. It is also capable of performing a number of other important functions, which will be discussed in more detail below.

About the functions of proteins

Proteins are capable of performing not only the function of growth (which is so interesting to bodybuilders), but also many other, equally important ones:

The human body is a smart system that itself knows how and what should function. So, for example, the body knows that protein can act as a source of energy for work (reserve forces), but it will be inappropriate to spend these reserves, so it is better to break down carbohydrates. However, when the body contains a small amount of carbohydrates, the body has no choice but to break down protein. So it is very important to remember to have enough carbohydrates in your diet.

Each individual type of protein has a different effect on the body and promotes muscle growth in different ways. This is due to the different chemical composition and structural features of the molecules. This only leads to the fact that the athlete needs to remember the sources of high-quality proteins, which will act as building materials for muscles. Here the most important role is given to such a value as the biological value of proteins (the amount that is deposited in the body after consuming 100 grams of proteins). Another important nuance is that if the biological value is equal to one, then this protein contains the entire necessary set of essential amino acids.

Important: Let’s consider the importance of biological value using an example: in a chicken or quail egg the coefficient is 1, and in wheat it is exactly half (0.54). So it turns out that even if the products contain the same amount of necessary proteins per 100g of product, more of them will be absorbed from eggs than from wheat.

As soon as a person consumes proteins internally (with food or as food additives), they begin to break down in the gastrointestinal tract (thanks to enzymes) into simpler products (amino acids), and then into:

Water;
Carbon dioxide;
Ammonia.

After this, the substances are absorbed into the blood through the intestinal walls, and then transported to all organs and tissues.

Such different proteins

The best protein food is considered to be that of animal origin, as it contains more nutrients and amino acids, but plant proteins should not be neglected. Ideally the ratio should look like this:

70-80% of food is of animal origin;
20-30% of food is of plant origin.

If we consider proteins according to their degree of digestibility, they can be divided into two large categories:

Fast. Molecules are broken down to their simplest components very quickly:

Fish;
Chicken breast;
Eggs;
Seafood.

Slow. The molecule breaks down to its simplest components very slowly:

Cottage cheese.

If we look at protein through the lens of bodybuilding, it means highly concentrated protein (protein). The most common proteins are considered to be (depending on how they are obtained from foods):

From whey - is the fastest absorbed, extracted from whey and has the highest biological value;
From eggs - absorbed within 4-6 hours and is characterized by a high biological value;
From soybeans - a high level of biological value and rapid absorption;
Casein - takes longer to digest than others.

Vegetarian athletes need to remember one thing: vegetable protein (from soy and mushrooms) is incomplete (particularly in terms of amino acid composition).

Therefore, do not forget to take all this important information into account when shaping your diet. It is especially important to take into account essential amino acids and maintain their balance when consuming. Next, let's talk about the structure of proteins

Some information about the structure of proteins

As you already know, proteins are complex high-molecular organic substances that have a 4-level structural organization:

Primary;
Secondary;
Tertiary;
Quaternary.

It is not at all necessary for an athlete to delve into the details of how the elements and connections in protein structures are arranged, but we now have to deal with the practical part of this issue.

Some proteins are absorbed within a short period of time, while others require much more. And this depends, first of all, on the structure of proteins. For example, proteins in eggs and milk are absorbed very quickly due to the fact that they are in the form of individual molecules that are curled into balls. In the process of eating, some of these connections are lost, and it becomes much easier for the body to assimilate the changed (simplified) protein structure.

Of course, as a result of heat treatment, the nutritional value of foods decreases somewhat, but this is not a reason to eat foods raw (do not boil eggs or boil milk).

Important: if you want to eat raw eggs, then instead of chicken eggs you can eat quail eggs (quails are not susceptible to salmonellosis, since their body temperature is more than 42 degrees).

When it comes to meat, their fibers are not originally intended to be eaten. Their main task is to generate strength. It is because of this that the meat fibers are tough, cross-linked and difficult to digest. Cooking meat makes this process a little easier and helps the gastrointestinal tract break down the cross-links in the fibers. But even under such conditions, it will take from 3 to 6 hours to digest the meat. As a bonus for such “torture,” creatine is a natural source of increased performance and strength.

Most plant proteins are found in legumes and various seeds. The protein bonds in them are “hidden” quite tightly, so in order to get them out for the body to function, it takes a lot of time and effort. Mushroom protein is also difficult to digest. The golden mean in the world of plant proteins is soy, which is easily digestible and has sufficient biological value. But this does not mean that soy alone will be enough; its protein is incomplete, so it must be combined with proteins of animal origin.

And now is the time to take a closer look at the foods that have the highest protein content, because they will help build sculpted muscles:

After carefully studying the table, you can immediately create your ideal diet for the whole day. The main thing here is not to forget about the basic principles of rational nutrition, as well as the required amount of protein that is consumed during the day. To reinforce the material, here is an example:

It is very important not to forget that you need to consume a variety of protein foods. There is no need to torture yourself and eat one chicken breast or cottage cheese for the whole week. It is much more effective to alternate foods and then sculpted muscles are just around the corner.

And there is one more question that needs to be dealt with.

How to evaluate protein quality: criteria

The material has already mentioned the term “biological value”. If we consider its values from a chemical point of view, then this will be the amount of nitrogen that is retained in the body (of the total amount received). These measurements are based on the fact that the higher the content of essential essential amino acids, the higher the nitrogen retention rates.

But this is not the only indicator. Besides this, there are others:

Amino acid profile (full). All proteins in the body must be balanced in composition, that is, the proteins in food with essential amino acids must fully correspond to those proteins found in the human body. Only under such conditions will the synthesis of its own protein compounds not be disrupted and redirected not towards growth, but towards decay.

Availability of amino acids in proteins. Foods that contain large amounts of dyes and preservatives have fewer amino acids available. Strong heat treatment also causes the same effect.

Ability to assimilate. This indicator reflects how long it takes for proteins to be broken down into their simplest components and then absorbed into the blood.

Protein recycling (clean). This indicator provides information on how much nitrogen is retained, as well as the total amount of protein digested.

Efficiency of proteins. A special indicator that demonstrates the effectiveness of a particular protein on muscle growth.

Level of protein absorption based on amino acid composition. Here it is important to take into account both the chemical importance and value, as well as the biological one. When the coefficient is equal to one, it means that the product is optimally balanced and is an excellent source of protein. Now is the time to take a more specific look at the numbers for each product in an athlete’s diet (see figure):

And now it's time to take stock.

The most important thing to remember

It would be wrong not to summarize all of the above and not highlight the most important thing to remember for those who are trying to learn how to navigate the difficult issue of creating an optimal diet for the growth of sculpted muscles. So if you want to properly include protein in your diet, then do not forget about such features and nuances as:

It is important that the diet is dominated by proteins of animal rather than plant origin (in a ratio of 80% to 20%);
It is best to combine animal and plant proteins in your diet;
Always remember the required protein intake according to body weight (2-3g per 1 kg of body weight);
Be mindful of the quality of the protein you consume (i.e. watch where you get it from);
Don't overlook amino acids that the body cannot produce itself;
Try not to deplete your diet and avoid biases towards certain nutrients;
To ensure that proteins are best absorbed, take vitamins and whole complexes.

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Proteins are complex organic compounds consisting of amino acids. Chemical analysis showed that the proteins consist of the following elements:

Carbon 50-55%

Hydrogen 6-7%

Oxygen 21-23%

Nitrogen 15-17%

Sulfur 0.3-2.5%.

Phosphorus, iodine, iron, copper and other macro- and microsubstances were also found in the composition of individual proteins.

The content of basic chemical elements may vary in individual proteins, with the exception of nitrogen, the average amount of which is characterized by the greatest constancy and is 16%. In this regard, there is a method for determining the amount of protein based on the nitrogen contained in it. Knowing that 6.25 grams of protein contains 1 gram of nitrogen, you can find the amount of protein by multiplying the found amount of nitrogen by a factor of 6.25.

2. 4. Amino acids.

Amino acids – carboxylic acids whose alpha carbon hydrogen atom is replaced by an amino group. Proteins are made up of amino acids. Currently, more than 200 different amino acids are known. There are about 60 of them in the human body, and proteins contain only 20 amino acids, which are called natural or proteinogenic. 19 of them are alpha amino acids, meaning that an amino group is attached to the alpha carbon atom of the carboxylic acid. The general formula of these amino acids is as follows.

Only the amino acid proline does not correspond to this formula; it is classified as an imino acid.

The chemical names of amino acids are abbreviated for brevity, for example, glutamic acid GLU, serine SEP, etc. Recently, only one-letter symbols have been used to write the primary structure of proteins.

All amino acids have common groups: -CH2, -NH2, -COOH, they impart general chemical properties to proteins, and radicals, the chemical nature of which is diverse. They determine the structural and functional characteristics of amino acids.

The classification of amino acids is based on their physicochemical properties.

According to the structure of radicals:

Cyclic - homocyclic FEN, TIR, heterocyclic TRI, GIS.

Acyclic - monoaminomonocarboxylic GLY, ALA, SER, CIS, TRE, MET, VAL, LEI, ILEY, NLEY, monoaminodicarbonic ASP, GLU, diaminomonocarbonic LIZ, ARG.

By formation in the body:

Replaceable - can be synthesized in the body from substances of protein and non-protein nature.

Essential - cannot be synthesized in the body, therefore they must be supplied only with food - all cyclic amino acids, TRE, VAL, LEI, IL.

Biological significance of amino acids:

They are part of the proteins of the human body.

They are part of the peptides of the human body.

Many low molecular weight biologically active substances are formed in the body from amino acids: GABA, biogenic amines, etc.

Some hormones in the body are derivatives of amino acids (thyroid hormones, adrenaline).

Precursors of nitrogenous bases that make up nucleic acids.

Precursors of porphyrins used for heme biosynthesis for hemoglobin and myoglobin.

Precursors of nitrogenous bases that make up complex lipids (choline, ethanolamine).

Participate in the biosynthesis of mediators in the nervous system (acetylcholine, dopamine, serotonin, norepinephrine, etc.).

Properties of amino acids:

Well soluble in water.

In an aqueous solution they exist as an equilibrium mixture of a bipolar ion, cationic and anionic forms of the molecule. Equilibrium depends on the pH of the environment.

NH3-CH-COOH NH3-CH-COO NH2-CH-COO

R + OH R R + H

Cationic form Bipolar ion Anionic form

Alkaline pH Acidic environment

Capable of moving in an electric field, which is used to separate amino acids using electrophoresis.

They exhibit amphoteric properties.

They can play the role of a buffer system, because can react as a weak base and a weak acid.

Chemical composition of proteins.

3.1. Peptide bond

Proteins are irregular polymers built from α-amino acid residues, the general formula of which in an aqueous solution at pH values close to neutral can be written as NH 3 + CHRCOO – . Amino acid residues in proteins are connected by an amide bond between the α-amino and α-carboxyl groups. Peptide bond between two-amino acid residues are usually called peptide bond , and polymers built from α-amino acid residues connected by peptide bonds are called polypeptides. A protein, as a biologically significant structure, can be either one polypeptide or several polypeptides that form a single complex as a result of non-covalent interactions.

3.2. Elemental composition of proteins

When studying the chemical composition of proteins, it is necessary to find out, firstly, what chemical elements they consist of, and secondly, the structure of their monomers. To answer the first question, the quantitative and qualitative composition of the chemical elements of the protein is determined. Chemical analysis showed present in all proteins carbon (50-55%), oxygen (21-23%), nitrogen (15-17%), hydrogen (6-7%), sulfur (0.3-2.5%). Phosphorus, iodine, iron, copper and some other macro- and microelements, in various, often very small quantities, were also found in the composition of individual proteins.

To determine the chemical nature of protein monomers, it is necessary to solve two problems: divide the protein into monomers and find out their chemical composition. The breakdown of protein into its component parts is achieved through hydrolysis - prolonged boiling of the protein with strong mineral acids (acid hydrolysis) or reasons (alkaline hydrolysis). The most commonly used method is boiling at 110°C with HCl for 24 hours. At the next stage, the substances included in the hydrolyzate are separated. For this purpose, various methods are used, most often chromatography (for more details, see the chapter “Research Methods...”). The main part of the separated hydrolysates are amino acids.

3.3. Amino acids

Currently, up to 200 different amino acids have been found in various objects of living nature. In the human body, for example, there are about 60 of them. However, proteins contain only 20 amino acids, sometimes called natural ones.

Amino acids are organic acids in which the hydrogen atom of the -carbon atom is replaced by an amino group - NH 2. Therefore, by chemical nature these are α-amino acids with the general formula:

H – C  – NH 2

From this formula it is clear that all amino acids include the following general groups: – CH 2, – NH 2, – COOH. Side chains (radicals - R) amino acids differ. As can be seen from Appendix I, the chemical nature of radicals is diverse: from the hydrogen atom to cyclic compounds. It is radicals that determine the structural and functional characteristics of amino acids.

All amino acids, except for the simplest aminoacetic acid glycine (NH 3 + CH 2 COO ) have a chiral C atom and can exist in the form of two enantiomers (optical isomers):

COO – COO –

NH3+ RR NH3+

L-isomerD-isomer

All currently studied proteins contain only L-series amino acids, in which, if we consider the chiral atom from the side of the H atom, the NH 3 +, COO  groups and the R radical are located clockwise. When constructing a biologically significant polymer molecule, the need to build it from a strictly defined enantiomer is obvious - from a racemic mixture of two enantiomers an unimaginably complex mixture of diastereoisomers would be obtained. The question of why life on Earth is based on proteins built specifically from L-, and not D--amino acids, still remains an intriguing mystery. It should be noted that D-amino acids are quite widespread in living nature and, moreover, are part of biologically significant oligopeptides.

Proteins are built from twenty basic α-amino acids, but the rest, quite diverse amino acids, are formed from these 20 amino acid residues already in the protein molecule. Among such transformations, we should first of all note the formation disulfide bridges during the oxidation of two cysteine residues in already formed peptide chains. As a result, a diaminodicarboxylic acid residue is formed from two cysteine residues cystine (See Appendix I). In this case, cross-linking occurs either within one polypeptide chain or between two different chains. As a small protein having two polypeptide chains, connected by disulfide bridges, as well as cross-links within one of the polypeptide chains:

GIVEQCCASVCSLYQLENYCN

FVNQHLCGSHLVEALYLVCGERGFYTPKA

An important example of modification of amino acid residues is the conversion of proline residues into residues hydroxyproline :

N – CH – CO – N – CH – CO –

CH 2 CH 2 CH 2 CH 2

CH2CHOH

This transformation occurs, and on a significant scale, with the formation of an important protein component of connective tissue - collagen .

Another very important type of protein modification is phosphorylation of hydroxyl groups of serine, threonine and tyrosine residues, for example:

– NH – CH – CO – – NH – CH – CO –

CH 2 OH CH 2 OPO 3 2 –

Amino acids in an aqueous solution are in an ionized state due to the dissociation of amino and carboxyl groups that are part of the radicals. In other words, they are amphoteric compounds and can exist either as acids (proton donors) or bases (donor acceptors).

All amino acids, depending on their structure, are divided into several groups:

Acyclic. Monoaminomonocarboxylic amino acids They contain one amine and one carboxyl group; they are neutral in an aqueous solution. Some of them have common structural features, which allows us to consider them together:

Glycine and alanine. Glycine (glycocol or aminoacetic acid) is optically inactive - it is the only amino acid that does not have enantiomers. Glycine is involved in the formation of nucleic and bile acids, heme, and is necessary for the neutralization of toxic products in the liver. Alanine is used by the body in various processes of carbohydrate and energy metabolism. Its isomer -alanine is a component of vitamin pantothenic acid, coenzyme A (CoA), and muscle extractives.

Serine and threonine. They belong to the group of hydroxy acids, because have a hydroxyl group. Serine is a component of various enzymes, the main protein of milk - casein, as well as many lipoproteins. Threonine is involved in protein biosynthesis, being an essential amino acid.

Cysteine and methionine. Amino acids containing a sulfur atom. The importance of cysteine is determined by the presence of a sulfhydryl (– SH) group in its composition, which gives it the ability to easily oxidize and protect the body from substances with high oxidative capacity (in case of radiation injury, phosphorus poisoning). Methionine is characterized by the presence of a readily mobile methyl group, which is used for the synthesis of important compounds in the body (choline, creatine, thymine, adrenaline, etc.)

Valine, leucine and isoleucine. They are branched amino acids that actively participate in metabolism and are not synthesized in the body.

Monoaminodicarboxylic amino acids have one amine and two carboxyl groups and give an acidic reaction in aqueous solution. These include aspartic and glutamic acids, asparagine and glutamine. They are part of the inhibitory mediators of the nervous system.

Diaminomonocarboxylic amino acids in an aqueous solution they have an alkaline reaction due to the presence of two amine groups. Lysine, which belongs to them, is necessary for the synthesis of histones and also in a number of enzymes. Arginine is involved in the synthesis of urea and creatine.

Phenyl-alanine serves as the main source for the synthesis of tyrosine, a precursor to a number of biologically important substances: hormones (thyroxine, adrenaline), and some pigments. Tryptophan, in addition to participating in protein synthesis, serves as a component of vitamin PP, serotonin, tryptamine, and a number of pigments. Histidine is necessary for protein synthesis and is a precursor of histamine, which affects blood pressure and gastric juice secretion.

Properties

Proteins are high molecular weight compounds. These are polymers consisting of hundreds and thousands of amino acid residues - monomers.

Proteins have a high molecular weight, some are soluble in water, are capable of swelling, and are characterized by optical activity, mobility in an electric field, and some other properties.

Proteins actively enter into chemical reactions. This property is due to the fact that the amino acids that make up proteins contain different functional groups that can react with other substances. It is important that such interactions also occur inside the protein molecule, resulting in the formation of peptide, hydrogen disulfide and other types of bonds. To amino acid radicals, and Accordingly, molecular mass proteins ranges from 10,000 to 1,000,000. Thus, ribonuclease (an enzyme that breaks down RNA) contains 124 amino acid residues and its molecular weight is approximately 14,000. Myoglobin (muscle protein), consisting of 153 amino acid residues, has a molecular weight 17,000, and hemoglobin - 64,500 (574 amino acid residues). Other proteins have higher molecular weights: β-globulin (forms antibodies) consists of 1250 amino acids and has a molecular weight of about 150,000, and the molecular weight of the enzyme glutamate dehydrogenase exceeds 1,000,000.

Chemical elements necessarily included in a protein molecule. Protein composition: what do we know about it? Initial stages in protein chemistry

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2.2 Theory of “carbon-nitrogen complexes” A.Ya. Danilevsky

According to Danilevsky, carbon-nitrogen complexes could be connected by an ether or amide bond to form a high-molecular structure.

2.3 Theory of “Kirins” A. Kossel

2.4 Peptide theory E. Fisher

2.5 Development of methods for amino acid synthesis

In order to move on to the synthesis of amino acid derivatives connected by peptide bonds, Fischer did a lot of work on studying the structure and synthesis of amino acids.

2. 6 The crisis of the peptide theory

However, attempts to synthesize model compounds containing diketopiperazines yielded little for protein chemistry; the peptide theory subsequently triumphed, but these works had a stimulating effect on the chemistry of piperazines in general.

After the peptide and diketopiperase theories, attempts continued to prove the existence of only peptide structures in the protein molecule. At the same time, they tried to imagine not only the type of molecule, but also its general outline.

The original hypothesis was expressed by the Soviet chemist D.L. Talmud. He suggested that the peptide chains within protein molecules are folded into large rings, which in turn was a step towards his creation of the idea of ​​a protein globule.

At the same time, data appeared indicating a different set of amino acids in different proteins. But the patterns governing the sequence of amino acids in the protein structure were not clear.

According to M. Bergman and K. Niemann, each amino acid occurs in the polypeptide chain at a certain interval or, as M. Bergman said, has a certain “periodicity.” This periodicity is determined by the nature of the amino acid residues.

They imagined the silk fibroin molecule as follows:

GlyAlaGlyTyr GlyAlaGlyArg GlyAlaGlyx GlyAlaGlyx

(GlyAlaGlyTyr GlyAlaGlyx GlyAlaGlyx GlyAlaGlyx) 12

GlyAlaGlyTyr GlyAlaGlyx GlyAlaGlyx GlyAlaGlyArg

(GlyAlaGlyTyr GlyAlaGlyx GlyAlaGlyx GlyAlaGlyx) 13

The Bergmann-Niemann hypothesis had a significant impact on the development of amino acid chemistry; a large number of works were devoted to its verification.

CHAPTER 3. CHEMICAL COMPOSITION OF PROTEINS

3.1 Peptide bond

3.2 Elemental composition of proteins

3.3. Amino acids

Currently, up to 200 different amino acids have been found in various objects of living nature. In the human body, for example, there are about 60 of them. However, proteins contain only 20 amino acids, sometimes called natural ones.

Amino acids are organic acids in which the hydrogen atom of the carbon atom is replaced by an amino group - NH 2. Therefore, by chemical nature these are amino acids with the general formula:

All amino acids, except for the simplest aminoacetic acid glycine (NH 3 + CH 2 COO) have a chiral C atom and can exist in the form of two enantiomers (optical isomers):

An important example of modification of amino acid residues is the conversion of proline residues into residues hydroxyproline :

This transformation occurs, and on a significant scale, with the formation of an important protein component of connective tissue - collagen .

Another very important type of protein modification is phosphorylation of hydroxyl groups of serine, threonine and tyrosine residues, for example:

Amino acids in an aqueous solution are in an ionized state due to the dissociation of amino and carboxyl groups that are part of the radicals. In other words, they are amphoteric compounds and can exist either as acids (proton donors) or bases (donor acceptors).

All amino acids, depending on their structure, are divided into several groups:

Acyclic. Monoaminomonocarboxylic amino acids They contain one amine and one carboxyl group; they are neutral in an aqueous solution. Some of them have common structural features, which allows us to consider them together:

Serine and threonine. They belong to the group of hydroxy acids, because have a hydroxyl group. Serine is a component of various enzymes, the main protein of milk - casein, as well as many lipoproteins. Threonine is involved in protein biosynthesis, being an essential amino acid.

Valine, leucine and isoleucine. They are branched amino acids that actively participate in metabolism and are not synthesized in the body.

Monoaminodicarboxylic amino acids have one amine and two carboxyl groups and give an acidic reaction in aqueous solution. These include aspartic and glutamic acids, asparagine and glutamine. They are part of the inhibitory mediators of the nervous system.

Diaminomonocarboxylic amino acids in an aqueous solution they have an alkaline reaction due to the presence of two amine groups. Lysine, which belongs to them, is necessary for the synthesis of histones and also in a number of enzymes. Arginine is involved in the synthesis of urea and creatine.

CHAPTER 4. STRUCTURE

When studying the composition of proteins, it was found that they are all built on a single principle and have four levels of organization: primary, secondary, tertiary, and some of them quaternary structures.

4.1 Primary structure

It is a linear chain of amino acids arranged in a specific sequence and connected by peptide bonds. Peptide bond is formed due to the -carboxyl group of one amino acid and the -amine group of another:

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2. 4. Amino acids.

The original hypothesis was expressed by the Soviet chemist D.L. Talmud. He suggested that the peptide chains within protein molecules are folded into large rings, which in turn was a step towards his creation of the idea of a protein globule.