The natural role of amino acids, proteins, and peptides in the proper functioning and renewal of the body

Amino acids of varying chain lengths and different sequences can form dimers and polymers. Depending on the number of amino acid residues located on the polymer chain, polymers are divided into peptides and proteins. Peptides contain about 50 amino acids in their structure, and proteins contain a larger number of amino acid residues than peptides in one or several chains. Both amino acids, proteins, and peptides play an important role in the proper functioning of the organism. Thanks to modern peptide therapies, regeneration of the body can be allowed.

Keywords: peptide · amino acid · protein · α-helix · β-structure · nonpolar chain · alanine · valine · leucine · isoleucine · phenylalanine · tryptophan · methionine · proline · glycine · serine · threonine · tyrosine · cysteine · asparagine · glutamine · aspartic acid · glutamic acid · configuration · conformation · dipeptide · oligopeptide · peptide bond · growth hormone

List of abbreviations: ACTH - adrenocorticotropin; CRH - corticoliberin; POMC - proopiomelanocortin; MMC - migrating motor complex; GRPP - glycentin-dependent pancreatic polypeptide; HGH - growth hormone. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body, presented below, will allow familiarization with their action and the possibilities they carry.

Characteristics of amino acids

Amino acids, as some of the best-known components of living organisms, occur as derivatives of organic acids, where at least one hydrogen atom is replaced by an amino group. They are components commonly found both in free form and bound - in the case of peptides or proteins. Each of the amino acids found in proteins, except for proline and hydroxyproline, has an amino group located at the α carbon and an R side chain, which can have different structures and is connected to the same carbon atom. 

General formula of an amino acid. 

A. In free form

B. In the form of a zwitterion. About 300 amino acids are known in the environment, but 22 are commonly found, of which 2 additional ones have been relatively recently discovered and occur only in certain proteins. The presence and location in the protein structure of the already known amino acids are determined by genetic properties; in some cases, this is the result of post-translational modification of amino acid residues that were previously incorporated into the protein chain. Other amino acids may occur in free form or in non-protein compounds. The role of an amino acid in a protein is determined by the structure of its side chain, through which the classification of amino acids is defined into several groups, depending on the nature of the side chains possessed by the amino acid.

Amino acids with nonpolar side chains

The group of amino acids with nonpolar side chains includes, in order: alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, proline, and glycine. There is a certain relationship between the last two mentioned amino acids. Proline, as an unusual example, does not have an α-amino group but an imino group, which is incorporated into the structure of the pyrrolidine ring. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body Glycine, on the other hand, does not have a side chain, which is replaced by a hydrogen atom. Each of the mentioned amino acids has a nonpolar side chain that does not have the ability to gain or lose protons and does not participate in forming hydrogen or ionic bonds. The side chain is most often treated as lipophilic, i.e., hydrophobic—not binding water. Such chains avoid aqueous environments by sticking to each other and are directed toward the interior of the protein molecule. When in an aqueous environment, their behavior is best compared to that of oil droplets, which combine into larger droplets, thereby reducing contact with water. 

Amino acids with polar side chains without charge

The group of amino acids with polar side chains without charge includes: serine, threonine, tyrosine, cysteine, asparagine, and glutamine. These amino acids have a zero charge at neutral pH, but in the case of cysteine and tyrosine, they can lose a proton at alkaline pH. Serine, threonine, and tyrosine are capable of forming hydrogen bonds due to the presence of a polar hydroxyl group. Also, in the case of the side chains of asparagine and glutamine, hydrogen bonds can be formed due to the presence of carbonyl and amide groups. The amide group of asparagine as well as the hydroxyl groups of serine and threonine can be sites for sugar component binding. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body.

Amino acids with acidic side chains

The group of amino acids with acidic side chains includes aspartic acid and glutamic acid. The side chains of these amino acids contain carboxyl groups. At neutral pH, they undergo complete dissociation, becoming carriers of a negative charge. The fully ionized forms of aspartic acid and glutamic acid are called aspartate and glutamate. The resulting transformed names, after ionization, indicate that at physiological pH they exist as anions. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body    

Amino acids with basic side chains

Amino acids with basic side chains. The group of amino acids with basic side chains includes: lysine, arginine, and histidine. The side chains of these amino acids contain groups capable of binding protons. These groups include the ε-amino group of lysine, the guanidino group of arginine, and the imidazole ring of histidine. At physiological pH, the R groups of lysine and arginine are fully ionized, thus acquiring a positive charge. The free amino acid histidine has a slightly basic character, existing in a neutral form at physiological pH. However, it can happen that histidine in a protein has an R group that is either positively charged or neutral, depending on the environment created by the protein. This plays an important role in the function of the protein hemoglobin.

Proteins

Characteristics of proteins

Proteins, as condensation polymers of amino acids that are abundant in the human body, are a fundamental structural component for its proper functioning. Composed exclusively of amino acid residues, they are called simple proteins or proteins. Complex proteins, proteids, additionally contain a prosthetic group that is not a protein component. As macromolecular products, they are formed by the interaction of the α-carboxyl group of one amino acid with the α-amino group of another amino acid, creating a peptide bond. Proteins with a molecular mass greater than 10,000 daltons (Da) can be called polypeptides. All proteins with a lower molecular mass are called oligopeptides. Each protein has a protein chain consisting of 100 to 1000 amino acid residues.

Primary structure

The primary structure of the polypeptide chain of a given protein determines the order (sequence) of the connection of amino acid residues in the polypeptide chain. Individual amino acids are covalently linked by peptide bonds. Only specific amino acid sequences occur in proteins due to the vast possibility of combinations. The arrangement of amino acid residues along the polypeptide chain is not strictly and clearly defined. Using the example of a protein molecule such as hemoglobin, one can point to the importance of the primary structure. In this case, replacing one amino acid with another results in the formation of pathological hemoglobin. To better understand the essence of its formation, for example, at position six, glutamic acid is replaced by another amino acid (valine or lysine), which leads to negative biological consequences. Red blood cells undergo a biologically altered state, causing the shape of the cells to change to an atypical form. The cells become susceptible to hemolysis, which simultaneously causes a decrease in the number of erythrocytes in the blood. The breakdown products of erythrocytes are captured by the liver and spleen, and the concentration of the bile pigment, bilirubin, increases as a result of heme breakdown in hemoglobin. The consequence of these processes is the development of a disease state known as hemolytic anemia.

Secondary structure

Speaking of secondary structure, the basic terms are configuration and conformation. While configuration refers to the geometric relationships between specific sets of atoms, conformation refers to the spatial structure of the protein. In the case of configuration, there is a mutual change in the construction of already formed bonds, for example, the transformation of D-alanine into L-arginine. Such a conversion can be achieved by breaking existing covalent bonds and forming them anew. Conformation, on the other hand, does not lead to the breaking of covalent bonds but to the breaking and reformation of non-covalent forces such as hydrogen bonds or hydrophobic interactions. Only some of the resulting conformations have biological significance. The most common form of protein secondary structure is the α-helix in spiral form. There are 3.6 amino acid residues per turn of the α-helix. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the organism. The specific and distinct spiral form allows the formation of hydrogen bonds, both intra-chain and inter-turn, with maximum strength due to the possibility of electrostatic interactions. The α-helix structure, which includes the peptide bond of the protein chain, allows it to participate in forming hydrogen bonds except for bonds involving the imino groups of proline. Polypeptides synthesized from L-amino acids or D-amino acids spontaneously form an α-helix structure. Polypeptides formed from amino acid racemates and polymers of certain amino acids, e.g., proline or hydroxyproline, do not have the ability to spontaneously form it. For example, α-keratin, a protein found, among other places, in hair and almost entirely composed of α-helix structure, whereas collagen or elastin, which contain the mentioned proline and hydroxyproline, have no ability to form this structure.

Tertiary structure 

The tertiary structure allows the preservation of the secondary structure while the protein molecule is folded in three dimensions. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the organism 7 The spatial packing of the protein molecule is mainly determined by the primary structure, and indirectly also by the secondary structure. The tertiary structure is stabilized by interactions between the side chains of amino acid residues, including covalent bonds, in this case hydrogen bridges, as well as by low-energy non-covalent bonds, i.e., hydrogen bonds. In aqueous solutions, the structure of globular proteins is compact. Hydrophobic side chains of amino acid residues are hidden inside the molecule, while hydrophilic groups are located on the molecule's surface. Polar groups, including those hidden inside the molecule, together with the components of peptide bonds, allow the formation of hydrogen bonds as well as electrostatic interactions. The tertiary structure forms only when bonds exist that allow the linking of amino acid residues that are linearly distant from each other.

Quaternary structure 

The last of the presented structures occurs only in some proteins and defines the spatial arrangement and subunit composition with respect to a single protein molecule. In this case, proteins have a high molecular weight and consist of two or more monomers, i.e., peptide chains. Usually, in the case of quaternary structure, the protein elements involved in its formation are connected by low-energy hydrogen bonds. In some cases, the structure is stabilized by disulfide bridges between cysteine residues. In the case of collagen and elastin, the covalent bonds between subunits are exceptionally stable. The biological properties of the quaternary structure can be modified by small molecules known as allosteric effectors. In the case of hemoglobin and enzymatic proteins, especially lactate dehydrogenase, the quaternary structure is very well understood. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the organism.

Peptides

Characteristics of peptides

Peptides are chemical compounds built similarly to proteins, from amino acids. They are the subject of wide interest, performing important biological functions. Many hormones as well as neurotransmitters are peptides. In the case of endogenous peptides, they act antimicrobial, serving as the body's defense system. Naturally occurring peptides and their synthetic analogs are considered attractive compounds of therapeutic significance due to their high activity, low toxicity, and lack of drug interactions. In medical practice, only a few peptides are used due to biological instability and rapid degradation, but peptide synthesis allows obtaining stable forms. Similarly, for example, in the synthesis of peptides from natural sources, which are used, among others, for vaccine production. The product formed from the reaction of two amino acids is called a dipeptide, maintaining a free amino group of one amino acid and a free carboxyl group of the other amino acid. Peptides composed of several to a dozen amino acids are called oligopeptides, while longer peptides containing several dozen amino acid residues are polypeptides. Peptide nomenclature begins with the name of the N-terminal amino acid residue, then lists the names of subsequent amino acid residues, and ends with the name of the C-terminal amino acid. The sequence of amino acids is written using three-letter or one-letter symbols. Peptides occur in an unbranched form, having only two specific ends. One is called the amino end, where the amino acid with a free α-amino group is present. The other is called the carboxyl end or C-terminus, where the amino acid with a free α-carboxyl group is present.

Peptide bond

The carbon atom from the α-carboxyl group binds to the nitrogen atom of the α-amino group through a single bond, the peptide bond. It is presumed that this bond exists in the form of two structures that remain in a specific mutual equilibrium. The C-N bond converts to C=N and vice versa. Rotation around the C=N axis is not possible, which makes the peptide bond rigid enough to exhibit characteristics of a double bond. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the organism 9 In the case of a peptide bond involving the imino group of proline or hydroxyproline with the carboxyl group of another amino acid, a different, distinct structure is formed. In this case, the nitrogen is incorporated into the pyrrolidine ring structure, there is no hydrogen substituent, and thus rotation around the bonds formed in the presence of nitrogen is not possible. Amino acids involved in forming the peptide bond lose fragments of their molecules. These are -OH molecules from the carboxyl group and -H from the amino group. Therefore, amino acids present in peptides and proteins are called amino acid residues. The resulting peptide bonds are stable and their breakdown can only occur under the action of strong bases and acids at simultaneously high temperatures. 

Biologically active peptides

Peptide hormones and protein hormones are commonly found in the environment around us. Previously, they were mostly known as unstable forms. Through synthesis, it is increasingly possible to select peptide therapy that will be durable and effective depending on the needs of the organism. That is why it is worth skillfully and safely experimenting with hormone stimulation. Considering some peptides that are biologically active, we can take glutathione as an example, which, being a tripeptide with a specific structure, is composed of glutamate, cysteine, and glycine. Glutamate occurs as the N-terminal amino acid. However, the bond between glutamate and cysteine is unusual for peptides and proteins because it does not involve the α-carboxyl group of glutamate but the γ-carboxyl group. Therefore, glutathione exists in reduced and oxidized forms, being γ-glutamylcysteinylglycine. In the reduced form, it has a free sulfhydryl group, and in the oxidized form, a pair of hydrogen atoms detach from the –SH groups. The sulfur atoms remain without hydrogen, resulting in the formation of a disulfide bridge. The modification ability of glutathione in its oxidized or reduced state is important in redox processes. Examples also include oxytocin and vasopressin, which are nanopeptides produced by hypothalamic neurons and released by the posterior pituitary gland, differing by only two amino acids. Cysteine occurs in two positions, leading to the formation of a disulfide bridge. Oxytocin acts as a hormone stimulating uterine contraction activity. Vasopressin, on the other hand, stimulates water reabsorption in the kidney tubules. Vasopressin also plays an important role in regulating the secretion of adrenocorticotropic hormone (ACTH) during stress situations. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the organism.

Peptide hormones

Adrenocorticotropic hormone (ACTH)

Adrenocorticotropic hormone, as a 39-amino acid peptide, is produced as a result of the degradation of a much larger precursor molecule called proopiomelanocortin (POMC). Proopiomelanocortin also serves as a source of other active peptides. Two peptides are contained within the ACTH structure. These include the α-melanotropin hormone (α-MSH), which is identical in structure to the first 13 amino acids of ACTH, and the intermediate lobe pituitary peptide similar to corticotropin—the 18-39 fragment of ACTH. The primary function of ACTH is considered to be the stimulation of the adrenal cortex so that it is capable of secreting steroid hormones. Adrenocorticotropic hormone is responsible for regulating activity at the level of the zona fasciculata and reticularis. The biological activity of ACTH is attributed to the first 18 amino acids. ACTH regulation occurs through corticoliberin (CRH), a hormone found in the hypothalamus, which releases corticotropin via cortisol through negative feedback. This means that cortisol deficiency stimulates CRH and ACTH, while its excess inhibits their secretion. Thus, by releasing cortisol, many vital functions are regulated, including mobilizing the body to stressful conditions, increasing blood pressure, and anti-inflammatory capabilities. ACTH is secreted in a pulsatile circadian rhythm, meaning its highest concentration is observed in the morning hours when it is most needed, then decreases throughout the day. Increased ACTH secretion is observed in pathological conditions such as adrenal cortex insufficiency, Cushing's disease, or Nelson's syndrome.

Insulin and C-peptide

Insulin and C-peptide are secreted in the pancreas by the human body continuously. During insulin production, in the process of its biosynthesis, C-peptide is produced. Pancreatic cells first produce preproinsulin, which undergoes further modification by the removal of amino acids, leading to the formation of proinsulin composed of two chains, A and B, which are connected by the C-peptide. Then, the C-peptide is detached from proinsulin, resulting in the final form. When glucose appears in the body, the pancreas receives a signal to release granules containing stored insulin and C-peptide molecules. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body. C-peptide is maintained in the liver much longer than insulin because it is not degraded there. Its breakdown mainly occurs in the kidneys. In the case of both insulin and C-peptide, elevated or too low concentrations lead to the development of type I or II diabetes as well as Cushing's disease. In the case of C-peptide, fluctuations in concentration may also indicate chronic kidney failure or the presence of metastases or local tumor recurrence, which is why maintaining proper concentration norms is so important.

Motilin

Motilin is a hormone associated with the smooth muscles of the stomach and intestines, controlled by vagus nerve fibers. It is synthesized in endocrine cells. As a peptide hormone composed of 22 amino acids arranged in a specific sequence, it is produced by cells of the small intestine. Produced by endocrine cells of the digestive system M (Mo), it participates in regulating gastrointestinal motility. Motilin is an important hormone involved in the initiation of phase III of the migrating motor complex (MMC), during which the stomach and small intestine are tasked with emptying the stomach of unnecessary food residues and exfoliated epithelial cells by stimulating peristaltic movements. The hormone also influences the emptying of the gallbladder during the interdigestive period at the highest motilin concentration.

Glucagon

Glucagon is one of the hormones involved in regulating glucose concentration; this peptide is secreted by the endocrine cells of the pancreas. It is a polypeptide composed of 29 amino acids, derived from a precursor consisting of 180 amino acids. Changes in glucose concentration allow for the secretion of glucagon. The production of the hormone glucagon occurs in the pancreatic islets, where glucagon as well as glicentin-related pancreatic polypeptide (GRPP) are formed from proglucagon. The main role of glucagon is to maintain the proper glucose concentration in the serum during its decrease between meals or during physical exertion. Its reserves in such situations are released from the liver to provide the body with adequate protection. Additionally, it may participate in regulation during food intake, which can cause the feeling of satiety to appear earlier. Glucagon potentially can inhibit the release of ghrelin and also inhibit intestinal peristalsis. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body

Protein hormones

Growth Hormone HGH Growth Hormone HGH is also called somatotropin. It is produced by acidophilic cells belonging to the anterior pituitary lobe. The hormone leads to increased proliferation of cells in various tissues, resulting in an increase in their number and size. HGH consists of 190 amino acids in the form of a simple polypeptide chain. In the body, it is released pulsatile every approx. 3-4 hours, with its highest concentrations recorded at night. The hormone secretion process is regulated by hypothalamic hormones characterized by opposing actions. These hormones include the growth hormone-releasing hormone GN-RH and the hormone inhibiting its release SRIF. During the release of somatotropin, this process is regulated by neurohormones: somatoliberin (GHRH), somatostatin (GHIH), ghrelin, glucocorticoids, fatty acids, glucose, insulin, and sex hormones. Growth hormone regulates metabolic processes, body growth modulation, stimulation, and proliferation of cells. The action of HGH is quite broad and includes, among others, stimulation of long bone growth, nucleic acid synthesis, and regulation of carbohydrate metabolism. Growth hormone has wide applications among athletes. Administration of somatotropin in athletes affects strengthening, muscle building, and minimizing injuries during training by developing connective tissue that forms cartilage. When deciding to take growth hormone, it is also important to maintain other factors such as sufficient sleep and a proper diet. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body

Conclusions

As mentioned above, amino acids, proteins, and peptides participate in the proper functioning of the body. In the case of peptides, it can be concluded that their skillful use allows for safe, effective, and satisfactory health therapy. Considering their action, they are recommended for use in almost all cases and for all people. They are especially recommended for athletes for regenerative and preventive purposes. Deficiencies of both protein hormones and peptide hormones can lead to serious disorders in the functioning of the body. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body.

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