The biological role of amino acids, proteins and peptides in the proper functioning and regeneration of the body

Amino acids of different 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 approximately 50 amino acids in their structure, while proteins contain a greater number of amino acid residues in one or more chains than peptides. Amino acids, proteins, and peptides all play an essential role in the proper functioning of the body. Modern peptide therapies allow for the regeneration of the body.

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- glicentin-related pancreatic polypeptide; HGH- human growth hormone. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body, presented in the following manner, will allow for familiarization with their action and the possibilities they carry.

Characteristics of Amino Acids

Amino acids, as one 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 commonly occurring components, present in both free and bound form — in the case of peptides or proteins. Each of the amino acids occurring in proteins, with the exception of proline and hydroxyproline, has an amino group located at the α carbon and a side chain R, which can have a different structure and is connected by the same carbon atom.

General formula of an amino acid.

A. In free form

B. In the form of a zwitterion. Approximately 300 amino acids are known in the environment, however 22 commonly occur in it, of which 2 additional ones have been discovered relatively recently and occur only in certain proteins. The presence and location in the protein structure of already known amino acids is 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. The remaining amino acids may occur in free form or in non-protein combinations. The role of an amino acid in a protein is determined by the structure of its side chain, whereby 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 Chains

The group of amino acids with nonpolar chains includes, in order: alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, proline, and glycine. In the case of the last two mentioned amino acids, a certain dependency exists. Proline, as an atypical example, does not possess an α-amino group but rather 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 possess a side chain, where it is replaced by a hydrogen atom. Each of the mentioned amino acids has a nonpolar side chain, which has no ability to acquire or lose protons and does not participate in the formation of hydrogen or ionic bonds. The side chain is most often treated as lipophilic, i.e. hydrophobic — not binding water. Such chains avoid the aqueous environment by adhering to each other and are directed toward the interior of the protein molecule. When found in an aqueous environment, their behavior is best compared to the behavior of oil droplets — they combine into larger droplets, simultaneously reducing contact with water in this way.

Amino Acids with Uncharged Polar Side Chains

The group of amino acids with uncharged polar side chains includes: serine, threonine, tyrosine, cysteine, asparagine, and glutamine. The presented amino acids have zero charge in an environment with neutral pH, however in the case of cysteine and tyrosine, at alkaline pH, they may lose a proton. Serine, threonine, and tyrosine are capable of forming a hydrogen bond due to possessing a polar hydroxyl group. Hydrogen bonds can also be formed in the case of the side chains of asparagine and glutamine due to their possessed carbonyl and amide groups. The amide group of asparagine as well as the hydroxyl groups of serine and threonine may be sites of binding of sugar components. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body.

Amino Acids with Acidic Chains

The group of amino acids with acidic chains includes aspartic acid and glutamic acid. Carboxyl groups are visible in the structure of the side chains of these amino acids. In an environment of neutral pH they undergo complete dissociation, becoming carriers of a negative charge. The completely ionized forms of aspartic acid and glutamic acid are called aspartate and glutamate. The resulting, transformed names, after ionization, indicate that in an environment with a physiological pH value they are anions. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body.

Amino Acids with Basic Chains

Amino acids with basic chains. The group of amino acids with basic 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 have been completely ionized, thereby gaining a positive charge. The free amino acid histidine has a slightly basic character, occurring in the environment in a neutral form at physiological pH. It may happen, however, that histidine in a protein will have an R group that is positively charged or neutral, depending on the environment created by the protein. This plays an essential role in the functioning of the protein known as hemoglobin.

Proteins

Characteristics of Proteins

Proteins, as condensation polymers of amino acids that occur abundantly in the human body, are the primary structural component for its proper functioning. Those built exclusively from amino acid residues are referred to as simple proteins, i.e. proteines. Complex proteins, proteids, additionally contain a prosthetic group that is not a protein component. As high-molecular-weight products, they are formed as a result of the interaction of the α-carboxyl group of an amino acid with the α-amino group of an amino acid, forming a peptide bond. Proteins whose molecular weight is greater than 10,000 daltons (Da) can be called polypeptides. All proteins with a lower molecular weight are referred to as oligopeptides. Each protein has a protein chain consisting of between 100 and 1,000 amino acid residues.

Primary Structure

The primary structure of the polypeptide chain of a given protein determines the order (sequence) of connection of amino acid residues in the polypeptide chain. Individual amino acids are connected covalently through peptide bonds. Only specific amino acid sequences occur in proteins due to the large possibility of combinations. The arrangement of amino acid residues along the polypeptide chain is not strictly and clearly defined. Using the protein molecule hemoglobin as an example, one can point to the importance of the primary structure. In this case, the replacement of one amino acid with another subsequently causes the formation of pathological hemoglobin. To better understand the essence of its formation, for example, in the sixth position, glutamate is replaced by another amino acid (valine or lysine), which leads to the development of negative biological consequences. Red blood cells transition into a biologically altered state, leading to a change in the shape of the blood cells to an atypical one. The blood cells become susceptible to hemolysis, which simultaneously causes a reduction 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, i.e. bilirubin, is increased as a result of the breakdown of heme in hemoglobin. The consequence of these processes is the development of the pathological condition known as hemolytic anemia.

Secondary Structure

When speaking of secondary structure, the fundamental terms are the concepts of 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, a mutual change in the construction of already formed bonds occurs, for example, the transformation of D-alanine into L-arginine. Such a conversion can be achieved by breaking the existing covalent bonds and re-forming them. Conformation, on the other hand, will not lead to the breaking of covalent bonds, but to the breaking and re-formation of non-covalent forces, i.e. hydrogen bridges or hydrophobic interactions. Only some of the resulting conformations have biological significance. The most commonly encountered form of the secondary structure of a protein is the α helix in spiral form. One turn of the α helix corresponds to 3.6 amino acid residues. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body. The specific and distinct spiral form allows for the formation of hydrogen bonds, both intrachain and interturn, of maximum strength, due to the possibility of electrostatic interactions. The α helix structure encompassing the peptide bond of the protein chain allows for its participation in the formation of hydrogen bonds, with the exception of bonds involving the imino groups of proline. Polypeptides obtained by synthesis from L-amino acids or D-amino acids spontaneously form the α helix structure. In the case of polypeptides formed from amino acid racemates and polymers of certain amino acids, e.g. proline or hydroxyproline, they do not possess the ability to spontaneously form it. For example, α-keratin, which is a protein occurring in, among others, hair, is covered almost entirely by the α helix structure, whereas collagen or elastin, in which the aforementioned proline and hydroxyproline are present, has no ability whatsoever to form this structure.

Tertiary Structure

The tertiary structure allows for the preservation of the secondary structure, with the three-dimensional folding of the protein molecule. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body. The spatial packing of the protein molecule is primarily the responsibility of the primary structure, and indirectly also the secondary structure. The tertiary structure is stabilized by interactions between the side chains of amino acid residues, in the case of covalent bonds, including hydrogen bridges, as well as by non-covalent bonds possessing low energy, i.e. hydrogen bonds. In aqueous solutions, the structure of globular proteins is compact. The hydrophobic side chains of amino acid residues are hidden inside the molecule and hydrophilic groups are located on the surface of the molecule. Polar groups, including those hidden in the interior of the molecule, together with the constituent elements of peptide bonds, allow for the formation of hydrogen bonds as well as electrostatic interactions. The tertiary structure is formed only when bonds exist that allow for the joining of amino acid residues that are linearly distant from each other.

Quaternary Structure

The last of the presented structures occurs only in certain proteins and defines the spatial arrangement and subunit composition in reference to a single protein molecule. Proteins in this case have a high molecular weight and consist of two or more monomers, i.e. peptide chains. Usually in the case of the quaternary structure, the protein elements participating 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-molecule substances known as allosteric effectors. In the case of hemoglobin and enzymatic proteins, particularly 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 body.

Peptides

Characteristics of Peptides

Peptides are chemical compounds built, similarly to proteins, from amino acids. They are the subject of broad interest, fulfilling important biological functions. Many hormones as well as neurotransmitters are in fact peptides. In the case of endogenous peptides, they act antimicrobially, functioning as a defense system of the body. Naturally occurring peptides and their synthetic analogues are considered attractive compounds of therapeutic significance due to their high degree of activity, low toxicity, and lack of drug interactions. In medical practice, only a few peptides find application due to biological instability and rapid breakdown; however, peptide synthesis allows for the obtaining of stable forms. Similarly, for example, in the case of the synthesis of peptides from natural sources, which are used, among others, in the production of vaccines. The product formed from the reaction of two amino acids is called a dipeptide, with the free amino group of one amino acid and the free carboxyl group of the other amino acid preserved. Peptides that are composed of several to more than a dozen amino acids are referred to as oligopeptides, while longer peptides, containing several dozen amino acid residues, are called polypeptides. The nomenclature of peptides begins with the name of the residue of the N-terminal amino acid, followed by the names of the 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, possessing only two specific ends. One of them is called the amino terminus, where the amino acid with a free α-amino group occurs. The other is called the carboxyl terminus or C-terminus, where the amino acid with a free α-carboxyl group occurs.

Peptide Bond

Carbon, as a result of the reaction of the α-carboxyl group, binds to the nitrogen of the α-amino group by means of a single bond, a peptide bond. It is presumed that this bond forms in the form of two structures that remain in a specific, mutual equilibrium. The C-N bond transitions to C=N and vice versa. Rotation relative to the C=N axis is not possible, by which the peptide bond is sufficiently rigid that it possesses the characteristics of a double bond. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body. In the case of a peptide bond with the participation of the imino group of proline or hydroxyproline with the carboxyl group of another amino acid, a different, distinct structure is formed. The nitrogen in this case is incorporated into the structure of the pyrrolidine ring; the hydrogen substituent does not occur, by which there is no possibility of rotation relative to the bonds that form in the presence of nitrogen. Amino acids that participate in the formation of the peptide bond lose fragments of molecules. These are the -OH molecules from the carboxyl group and -H from the amino group. Therefore, amino acids that are found 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 temperature.

Biologically Active Peptides

Peptide hormones and protein hormones are commonly present in the surrounding environment. Previously known mostly as unstable forms. Under the influence of synthesis, peptide therapy can be increasingly boldly selected, which will be durable and effective depending on the needs of the body. That is precisely why it is worthwhile to skillfully and safely engage with hormone stimulation. Taking into account certain biologically active peptides, we can use glutathione as an example, which, being a tripeptide of specific structure, is built from glutamate, cysteine, and glycine. Glutamate occurs as the N-terminal amino acid. The connection of glutamate with cysteine is, however, atypical for peptides and proteins, because the α-carboxyl group of glutamate does not occur here, only the γ-carboxyl group. Glutathione, therefore, occurs in reduced and oxidized form, being γ-glutamylcysteinylglycine. In its reduced form it possesses a free sulfhydryl group, and in its oxidized form, a pair of hydrogen atoms is detached from the -SH groups. The sulfur atoms remain devoid of hydrogen, the consequence of which is the formation of a disulfide bridge. The ability of glutathione to be modified into an oxidized or reduced state is important in oxidation-reduction processes. Another example is also oxytocin and vasopressin, which, being nonapeptides produced by hypothalamic neurons and released by the posterior lobe of the pituitary gland, differ by only two amino acids. Cysteine occurs in two positions, thereby leading to the formation of a disulfide bridge. Oxytocin occurs as a hormone stimulating the contractile activity of the uterus. Vasopressin, on the other hand, stimulates the absorption of water in the renal tubules. Vasopressin also plays an important role in the regulation of adrenocorticotropic hormone (ACTH) secretion in stressful situations. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body.

Peptide Hormones

Adrenocorticotropic Hormone (ACTH)

Adrenocorticotropic hormone, as a 39-amino acid peptide, arises as a result of the degradation of a much larger precursor molecule, proopiomelanocortin (POMC). Proopiomelanocortin also serves as a source of other active peptides. Two peptides are contained within the structure of ACTH. These include α-melanotropic hormone (α-MSH), which is structurally identical to the first 13 amino acids of ACTH, and the corticotropin-like intermediate lobe peptide — fragment 18-39 of ACTH. The primary function of ACTH is considered to be the stimulation of the adrenal cortex in such a way that it is capable of secreting steroid hormones. Adrenocorticotropic hormone is responsible for the regulation of activity at the level of the zona fasciculata and zona reticularis. The first 18 amino acids are responsible for the biological activity of ACTH. The regulation of ACTH occurs through corticoliberin (CRH), a hormone present in the hypothalamus, releasing corticotropin through cortisol via negative feedback. This means that cortisol deficiency causes stimulation of CRH and ACTH, while its excess inhibits this secretion. In turn, by releasing cortisol, many important vital functions are regulated, including mobilization of the body to stressful conditions, elevation of blood pressure, and anti-inflammatory capabilities. ACTH secreted pulsatilely in a circadian rhythm means that its highest concentration is observed in the morning hours when it is most desired, then decreasing as the day progresses. An increase in ACTH secretion is observed in such pathological cases 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 at all times. During the production of insulin, in the process of its biosynthesis, C-peptide is produced. Pancreatic cells produce preproinsulin in the first stage, which is subjected to further modification through the detachment of amino acids, leading to the formation of proinsulin composed of two chains A and B, which are connected by C-peptide; subsequently, the detachment of the C-peptide from proinsulin occurs, which causes the formation of the final form. At the moment glucose appears in the body, the pancreas receives a signal to release granules with the stored insulin and C-peptide molecule. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body. C-peptide is retained in the liver much longer than insulin, due to the fact that it is not degraded there. Its breakdown occurs primarily in the kidneys. In the case of both insulin and C-peptide, elevated or excessively low concentration leads to the development of type I or type II diabetes as well as Cushing's disease. In the case of C-peptide, concentration fluctuations may also indicate chronic renal insufficiency or the presence of metastases or local tumor recurrence, which is why maintaining correct concentration norms is so important.

Motilin

Motilin is a hormone associated with the smooth muscles of the stomach and intestines, controlled by vagal nerve fibers. Synthesized in endocrine cells. As a peptide hormone built from 22 amino acids located 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 the regulation of gastrointestinal motility. Motilin is an important hormone participating in the formation of phase III of the migrating motor complex (MMC), in which the stomach and small intestine are tasked with emptying the stomach of unnecessary food remnants and exfoliated epithelial cells through the stimulation of peristaltic movements. The hormone additionally affects the emptying of the gallbladder during the interdigestive period at the highest concentration of motilin.

Glucagon

Glucagon is one of the hormones involved in the regulation of glucose concentration; this peptide is secreted by endocrine cells of the pancreas. It is a polypeptide composed of 29 amino acids, formed from a precursor of 180 amino acids in structure. Changes in glucose concentration allow for the secretion of glucagon. The production of the hormone glucagon occurs in the pancreatic islets, in which glucagon as well as glicentin-related pancreatic polypeptide (GRPP) are formed from proglucagon. The primary task of glucagon is to maintain the proper concentration of glucose in the serum during its decline between meals or during physical exertion. Its reserves in such situations are released from the liver to provide the body with appropriate protection. Additionally, it may participate in the regulation of food intake, whereby the feeling of satiety may appear earlier. Glucagon can potentially 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 lobe of the pituitary gland. The hormone leads to increased proliferation of cells of 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 pulsatilely approximately every 3-4 hours, and its highest concentrations are recorded at night. The process of hormone secretion is regulated by hypothalamic hormones characterized by opposing actions. These hormones include the hormone causing the release of growth 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, glucocorticosteroids, fatty acids, glucose, insulin, and sex hormones. Growth hormone regulates metabolic processes, modulation of body growth, and stimulation and proliferation of cells. The action of HGH is quite broad and includes, among others, stimulation of long bone growth, synthesis of nucleic acids, and regulation of carbohydrate metabolism. Growth hormone has broad application among people engaged in sport. Administration of somatotropin in athletes affects the strengthening and building of muscles as well as the minimization of injuries during training, through the development of connective tissue that forms cartilage. When making the decision to take growth hormone, it is also important to maintain other factors such as sufficient sleep and an appropriate 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 satisfying health therapy. Taking into account their action, they are indicated for use in almost all cases and for all persons. They are particularly recommended for athletes for regenerative and preventive purposes. Deficiencies of both protein hormones and peptide hormones can lead to serious disturbances in the functioning of the body. The biological role of amino acids, proteins, and peptides in the proper functioning and regeneration of the body.

Bibliography:

1. Bańkowski.E, Biochemia. 2020; 160(1-3):33-41
2. Dryweń.M, Dźwigała J, Znaczenie aminokwasów rozgałęzionych w żywieniu człowieka oraz w profilaktyce i przebiegu niektórych chorób. Medycyna Ogólna i Nauki o Zdrowiu; 2013; 3(1) 379-384
3. Darewicz.M, Borawska J, Minkiewicz P, Biologicznie aktywne peptydy uwalniane z białek żywności. 2015; 3(100) 26-41; DOI:10.15193/zntj/2015/100/037
4. Miyamoto.T, Detection and quantification of d-amino acid residues in peptides and proteins using acid hydrolysis. 2018; 775-782; DOI:10.1016/j.bbapap.2017.12.010
5. Bottecchia.C, Photocatalytic Modification of Amino Acids, Peptides, and Proteins. 2018; 26-42; DOI:10.1002/chem.201803074
6. Rutherfurd M, Amino acid analysis. 2009; 11.9.1-11.9.37; DOI:10.1002/0471140864.ps1109s58
7. Rob.M, Liskamp.J, Peptides and Proteins as a Continuing Exciting Source of Inspiration for Peptidomimetics. 2011; 1626-1653; DOI:10.1002/cbic.201000717
8. Lewandowski K, Lewiński A, Hormony peptydowe wydzielane w przewodzie pokarmowym. 2012: 12(1) 10-14
9. Klein A. Molekularne mechanizmy regulacji hormonalnej. Wydawnictwo Uniwersytetu Jagiellońskiego. 2010; 200-233
10. Marciniak. P, Szymczak.M, Hormony peptydowe. Postępy biologii komórki. 2011; 43-63
11. O'Neill.R, Murphy.R, Endocrinology. 2012; 30-45
12. Siewko.K, Szelachowska.M, Peptyd C jako czynnik ryzyka rozwoju cukrzycy typu 1 u krewnych I stopnia osób chorych na cukrzycę autoimmunologiczną. P2009; 60(5) 26-43
13. Romański.K, Goździewska.K, Grelina i motylina podobieństwa i różnice w regulacji aktywności motorycznej przewodu pokarmowego. 2008; 64(11) 5-19
14. Nylec.M, Olszanecka.M, Rola glukagonu w patogenezie cukrzycy typu II. 2010; 1734-3321
15. Hsiao.Y, Yamada.M, The Roles of Peptide Hormones and Their Receptors during Plant Root Development. 2020; 12(1) 22; DOI:10.3390/genes12010022
16. Imura.H, Nakai Y, Tanaka N, ACTH and related peptides. 2000; 41(5) 949-56
17. Brownstein M, Adrenocorticotropic hormone in the central nervous system. 2000; 22: 93-9
18. Itoh. A, Motilin and Clinical Application. 2001; 593-608; DOI:10.1016/S0196-9781(96)00333-6 19. Chen.C, Ghrelin and Motylin in The Gastrointestinal System. 2012; DOI:10.2174/138161212803216915
19. Drucker.D, Mechanisms of Action and Therapeutic Application of Glukagon like Peptide-1. Cell metabolism, 2018: 740-756; DOI:10.1016/j.cmet.2018.03.001
20. Bildingmaier. M, Growth hormone. 2009; 187-200
21. Lee.S, Park.H, Evaluation of the Bioefficacy of a Stabilized Form of Human Growth Hormone (SP-hGH). 2013; 45(10):722-727; DOI:10.1055/s-0033-1345126
22. Maciejewska.Z, Korek.E, Rola hormonu wzrostu, insulinopodobnego czynnika wzrostu typu 1 oraz greliny. 2016; 216-220