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# Protein composition and structure Proteins are essential biopolymers composed of amino acid monomers arranged into specific structures that dictate their function. ## 1. Protein composition and structure Proteins, also known as proteins (from the Greek "protos" meaning primary), are the most abundant biopolymers in cells, constituting approximately 50% of their dry weight. This high proportion is due to the multitude of crucial functions they perform, making them indispensable for life. Despite their vast diversity, protein molecules share fundamental similarities at the molecular level, characterized by a unity in their composition and structure [1](#page=1). ### 1.1 Amino acids: the building blocks of proteins The monomers of proteins are amino acids, which are small organic molecules with a similar structural framework. Each amino acid possesses an amino group (–NH$_{2}$), which imparts an alkaline character, and a carboxyl group (–COOH), which confers acidic properties. The presence of both groups results in the amphoteric nature of amino acid molecules [1](#page=1). There are numerous types of amino acids, but only 20 participate in protein synthesis. All these 20 amino acids are alpha-amino acids, meaning that the –NH$_{2}$ and –COOH groups are attached to the same carbon atom, known as the alpha-carbon. This alpha-carbon is also bonded to a third group, called the side chain or radical (R-group). The R-groups are what confer individuality to each amino acid. Some radicals are hydrophobic (nonpolar), while others are hydrophilic. Among the hydrophilic radicals, there are polar uncharged, positively charged (with an additional amino group), and negatively charged (with an additional carboxyl group) types. Two of the 20 standard amino acids contain sulfur. The specific characteristics of these amino acids influence the properties of the polymers they form [1](#page=1). > **Tip:** While 20 amino acids are commonly found in proteins, understanding the properties of their R-groups (hydrophobic, hydrophilic, charged) is crucial for predicting protein folding and interactions. ### 1.2 Polypeptide chains and the peptide bond Proteins are synthesized through condensation reactions. In this process, the carboxyl group (–COOH) of one amino acid reacts with the amino group (–NH$_{2}$) of another amino acid. This interaction results in the release of a water molecule and the formation of a covalent bond known as a peptide bond (–CO–NH–) between the two amino acids [3](#page=3). > **Example:** The formation of a peptide bond can be visualized as: > Amino acid 1 (R$_{1}$-COOH) + Amino acid 2 (H$_{2}$N-R$_{2}$) $\rightarrow$ R$_{1}$-CO-NH-R$_{2}$ + H$_{2}$O When two amino acids are linked by a peptide bond, they form a dipeptide; three amino acids form a tripeptide, and so on. The sequential linkage of a large number of amino acids results in the formation of a polypeptide, also known as a polypeptide chain. A protein molecule can consist of one or more polypeptide chains [3](#page=3). These polypeptide chains are linear and unbranched. Their "backbone" is formed by the repeating sequence of the fragment –NH–CH–CO–, with the R-groups projecting outwards. The chain begins with an amino group (N-terminus, or "nitrogen end") and terminates with a carboxyl group (C-terminus, or "carbon end"). Proteins are thus classified as hetero-biopolymers constructed from polypeptide chains made up of 20 different types of amino acids [3](#page=3). ### 1.3 Levels of protein structure The spatial arrangement of a protein molecule is described by four distinct levels of organization: primary, secondary, tertiary, and quaternary structure [4](#page=4). #### 1.3.1 Primary structure The primary structure of a protein refers to the specific number, type, and sequence of amino acids in its polypeptide chain. This sequence is maintained by the peptide bonds. For a polypeptide chain of average length (100–150 amino acid residues), a vast number of combinations are theoretically possible. However, only a small subset of these combinations are realized, which are not random but dictated by the cell's genetic program [4](#page=4). The primary structure is fundamental, as it determines all subsequent levels of organization, and consequently, the protein's properties and functions [4](#page=4). > **Example:** A single amino acid substitution in the hemoglobin protein can alter subsequent organizational levels, change its properties and function, modify red blood cell shape, and lead to sickle cell anemia [4](#page=4). #### 1.3.2 Secondary structure The repeating –NH–CH–CO– fragment in the polypeptide backbone allows for the formation of numerous hydrogen bonds between the –NH– and –CO– groups. This results in the regular folding of the polypeptide chain, known as the secondary structure. There are two primary types of secondary structure: the alpha-helix ($\alpha$-helix) and the beta-sheet ($\beta$-sheet) [4](#page=4). In an $\alpha$-helix, hydrogen bonds form between the –NH– and –CO– groups of amino acids that are separated by approximately three residues. In a $\beta$-sheet, hydrogen bonds form between amino acids that are further apart. Depending on the primary structure, a polypeptide chain can fold into $\alpha$-helices, $\beta$-sheets, or a combination of both [4](#page=4). #### 1.3.3 Tertiary structure and the active center Beyond the $\alpha$-helices and $\beta$-sheets, portions of the polypeptide chain that do not participate in these regular structures can bend at various angles, imparting an additional three-dimensional shape to the molecule. This further folding of the polypeptide chain in space is termed the tertiary structure [4](#page=4). The tertiary structure is primarily stabilized by various types of bonds and interactions between the R-groups of different amino acids. These include [5](#page=5): * **Hydrogen bonds:** Between polar R-groups [5](#page=5). * **Ionic bonds:** Between oppositely charged R-groups [5](#page=5). * **Hydrophobic interactions:** Hydrophobic side chains tend to orient towards the interior of the molecule, away from water, while hydrophilic side chains are oriented towards the surface [5](#page=5). * **Disulfide bridges:** Covalent bonds formed between the sulfur atoms of two cysteine amino acids [5](#page=5). Based on the overall shape of the polypeptide chain in its tertiary structure, proteins are classified as globular or fibrous [5](#page=5). * **Globular proteins:** These proteins are compact and spherical. The spatial proximity of distant amino acids in globular proteins creates an active center, a region containing functionally active groups that is crucial for the protein's function. Often, other centers, such as regulatory centers, also arise. Examples of globular proteins include enzymes, membrane proteins, and myoglobin (a protein that binds oxygen in muscle cells) [5](#page=5). * **Fibrous proteins:** These proteins have a more elongated, thread-like shape. Keratin, a protein found in hair, nails, and the stratum corneum of the skin, is an example of a fibrous protein [5](#page=5). > **Tip:** The active center of an enzyme, a type of globular protein, is where the substrate binds and the catalytic reaction occurs. Its specific 3D conformation is critical for enzymatic activity. #### 1.3.4 Quaternary structure and non-protein components Many proteins function solely based on their tertiary structure, being composed of a single polypeptide chain (e.g., myoglobin). However, other proteins are assembled from two or more polypeptide chains, which can be identical or different. Each of these individual polypeptide chains, possessing its own tertiary structure, is called a subunit. Proteins composed of multiple subunits exhibit quaternary structure [6](#page=6). Hemoglobin is a prime example of a protein with quaternary structure. It is composed of four polypeptide chains, two of which are identical to each other, and the other two are also identical to each other. The interactions that stabilize quaternary structure are similar to those in tertiary structure, including weak interactions and disulfide bridges. At the quaternary level, globular proteins can develop additional regulatory centers, while fibrous proteins can associate into stable bundles [6](#page=6). Some proteins also contain non-protein components in addition to their polypeptide chains. These non-protein parts can be metal atoms, carbohydrates, lipids, or other molecules. For instance, both myoglobin and each of the four polypeptide chains in hemoglobin are associated with a smaller, iron-containing organic molecule called a heme group [6](#page=6). --- # Protein functions and properties Proteins are essential macromolecules that perform a vast array of critical functions within biological systems and possess distinct chemical and physical properties. ### 2.1 Protein functions Proteins fulfill diverse roles, encompassing structural support, protection, movement, transport, signaling, regulation, and catalysis. Autotrophic organisms synthesize their own proteins, while heterotrophs obtain them through diet [8](#page=8). #### 2.1.1 Structural function Proteins are fundamental components of cellular structure, forming part of cell membranes, cytoplasm, and organelles. They also contribute to the assembly of supramolecular complexes within the cell [8](#page=8). * **Examples:** Glycoproteins and lipoproteins in the cell membrane, ribosomes (RNA and proteins), chromatin (DNA and proteins) [8](#page=8). #### 2.1.2 Protective function Proteins provide both passive (mechanical) and active (immune) defense. They contribute to the formation of protective structures and actively neutralize foreign substances and cells [8](#page=8). * **Examples:** Keratin (in scales, feathers, nails, horns, hair), fibrinogen (involved in blood clotting), antibodies [8](#page=8). #### 2.1.3 Motor function Proteins are integral to the structure of specialized organelles in muscle cells and are involved in the movement of cilia and flagella [8](#page=8). * **Examples:** Actin and myosin (form myofibrils and enable muscle cell contraction), dynein (contractile protein in cilia and flagella) [8](#page=8). #### 2.1.4 Transport function These proteins facilitate the movement of substances across the cell membrane and between the cell and its environment [8](#page=8). * **Examples:** Transport proteins in the cell membrane, hemoglobin [8](#page=8). #### 2.1.5 Receptor function Proteins embedded in the cell membrane are responsible for receiving signals from the external environment [8](#page=8). * **Examples:** Proteins in the cell membrane [8](#page=8). #### 2.1.6 Regulatory function Proteins play a crucial role in regulating various processes within the organism [8](#page=8). * **Examples:** Insulin, growth hormone [8](#page=8). #### 2.1.7 Catalytic function Similar to chemical catalysts, proteins, specifically enzymes, accelerate the rate of biochemical reactions within the cell [8](#page=8). * **Examples:** Oxidases, reductases, hydrolases [8](#page=8). ### 2.2 Protein properties Proteins exhibit several key physical and chemical properties, including hydrolysis, denaturation, renaturation, precipitation, and solubility. #### 2.2.1 Hydrolysis Under suitable conditions (appropriate pH, enzymes), the peptide bonds within a protein molecule can break, yielding constituent α-amino acids. This process requires water and is termed hydrolysis [9](#page=9). #### 2.2.2 Denaturation and renaturation Denaturation occurs when proteins are exposed to agents such as heat, radiation, strong acids and bases, concentrated salt solutions, heavy metals, and organic solvents. These factors disrupt the bonds that maintain the protein's native three-dimensional (native conformation) structure [9](#page=9). * Denaturation affects the quaternary (if present), tertiary, and secondary structures of a protein, leading to a loss of its biological activity [9](#page=9). * It is a graded process that can be temporary or permanent [9](#page=9). Renaturation is the process by which a denatured protein can regain its native conformation under appropriate conditions. This ability to renature demonstrates that the protein's primary structure fully dictates its spatial conformation. Within cells, denaturation and renaturation are involved in regulating protein activity and dependent processes. Denatured proteins have altered properties and lose their functions, readily aggregating and precipitating [10](#page=10) [9](#page=9). #### 2.2.3 Precipitation Precipitation is the aggregation of protein molecules resulting from the disruption of their aqueous (hydrational) shell. This can occur at high salt concentrations, where salt ions strip away these hydration shells, a process known as salting out [10](#page=10). * Precipitation is often reversible [10](#page=10). * Precipitated proteins are not denatured and can be redissolved [10](#page=10). #### 2.2.4 Solubility of globular proteins in water Most globular proteins are soluble in water because water forms a hydration shell around them. In contrast, fibrous proteins are insoluble in water due to their tendency to aggregate into fibers [10](#page=10). --- # Molecular basis of sickle cell anemia Sickle cell anemia arises from a single point mutation in a gene on chromosome 11, which dictates the production of the beta-globin chain of hemoglobin. This mutation causes glutamic acid, normally found at the sixth position of the polypeptide chain, to be replaced by the amino acid valine. This alteration leads to the synthesis of an abnormal hemoglobin, known as hemoglobin S, which is less soluble and has a reduced capacity to bind oxygen [7](#page=7). ### The molecular defect and its consequences #### Hemoglobin S structure and function The fundamental cause of sickle cell anemia is a specific genetic mutation. Normally, the sixth amino acid in the beta-globin chain of hemoglobin is glutamic acid. In individuals with sickle cell anemia, this is replaced by valine due to a single nucleotide substitution in the corresponding gene. This single amino acid change has profound effects on the hemoglobin molecule's properties. Hemoglobin S is less soluble than normal hemoglobin (hemoglobin A) and exhibits a decreased affinity for oxygen [7](#page=7). #### Red blood cell deformation The structural alteration in the hemoglobin S molecule leads to the deformation of red blood cells. Under conditions of low oxygen, hemoglobin S molecules tend to polymerize, forming rigid, rod-like structures within the red blood cell. This polymerization distorts the normally flexible, biconcave disc shape of red blood cells into a characteristic sickle or crescent shape [7](#page=7). #### Pathological outcomes The sickled red blood cells are less pliable and can obstruct blood flow in small blood vessels, leading to vaso-occlusion. This blockage can cause pain crises, organ damage, and other severe complications associated with the disease. Furthermore, the abnormal shape and rigidity of sickled cells make them more fragile and prone to premature destruction, both in the bloodstream and the spleen. This increased rate of red blood cell breakdown results in a chronic hemolytic anemia [7](#page=7). > **Tip:** The normal lifespan of a red blood cell is approximately 120 days. In sickle cell anemia, this lifespan is drastically reduced to only 10-20 days, contributing significantly to the anemic syndrome [7](#page=7). --- ## Common mistakes to avoid - Review all topics thoroughly before exams - Pay attention to formulas and key definitions - Practice with examples provided in each section - Don't memorize without understanding the underlying concepts

| Term | Definition | |------|------------| | Proteins | Also known as proteins, these are the most abundant biopolymers in cells, making up about 50% of their dry weight, and are essential for life due to their numerous important functions. | | Amino acids | Small organic molecules with a similar structure that serve as the monomers of proteins; each contains an amino group (alkaline) and a carboxyl group (acidic), giving it an amphoteric character. | | Alpha-amino acids | Amino acids where the amino group (–NH2) and the carboxyl group (–COOH) are attached to the same carbon atom, which is also bonded to a third group called the side chain or radical (R-group). | | Side chain (R-group) | The variable part of an amino acid that determines its individual properties; radicals can be hydrophobic, hydrophilic (polar uncharged, positively charged, or negatively charged), and some contain sulfur. | | Peptide bond | A covalent bond formed by a condensation reaction between the carboxyl group of one amino acid and the amino group of another, with the release of a water molecule (–CO–NH–). | | Polypeptide chain | A linear, unbranched chain formed by the sequential linking of many amino acids through peptide bonds; it has an N-terminus (with a free –NH2 group) and a C-terminus (with a free –COOH group). | | Primary structure | The specific sequence of amino acids in a polypeptide chain, determined by the number, type, and order of amino acids, and maintained by peptide bonds. | | Secondary structure | The regular folding of a polypeptide chain due to numerous hydrogen bonds forming between the –NH– and –CO– groups in the polypeptide backbone, resulting in either an alpha-helix or a beta-sheet. | | Alpha-helix | A type of secondary protein structure where the polypeptide chain coils into a spiral shape, stabilized by hydrogen bonds that form approximately every three amino acids. | | Beta-sheet | A type of secondary protein structure where the polypeptide chain folds into a pleated, accordion-like pattern, stabilized by hydrogen bonds formed across more than three amino acids. | | Tertiary structure | The additional three-dimensional folding of a polypeptide chain beyond its secondary structure, stabilized mainly by hydrogen bonds, ionic bonds between R-groups, hydrophobic interactions, and disulfide bridges. | | Active center | A specific region within the tertiary structure of a globular protein that contains functionally active groups crucial for the protein's function, often formed by the spatial proximity of distant amino acids. | | Globular proteins | Proteins with a compact, spherical three-dimensional shape, characterized by the spatial folding of their polypeptide chains, often containing an active center and playing roles like enzymes and transport proteins. | | Fibrillar proteins | Proteins with a relatively unfolded, thread-like molecular shape, such as keratin, which forms structural components like hair and nails. | | Disulfide bridges | Covalent bonds formed between the sulfur atoms of two cysteine amino acid residues, which help to stabilize the tertiary and quaternary structures of proteins. | | Quaternary structure | The arrangement of two or more polypeptide chains (subunits), each with its own tertiary structure, to form a functional protein complex, maintained by weak interactions and disulfide bridges. | | Hemoglobin | A protein with quaternary structure, composed of four polypeptide chains, responsible for oxygen transport in the blood. | | Myoglobin | A globular protein that binds oxygen in muscle cells, consisting of a single polypeptide chain. | | Non-protein components | Parts of a protein molecule that are not polypeptide chains, such as metal atoms, carbohydrates, or lipids (e.g., the heme group in myoglobin and hemoglobin). | | Sickle cell anemia | A genetic disorder caused by a point mutation in the gene for the beta-globin chain of hemoglobin, leading to the production of abnormal hemoglobin S and characteristic sickle-shaped red blood cells. | | Hydrolysis | A process where peptide bonds in a protein molecule are broken down into constituent alpha-amino acids through the addition of water, often facilitated by suitable pH conditions or enzymes. | | Denaturation | The process where a protein loses its natural spatial structure (native conformation) due to the disruption of stabilizing bonds by factors like heat, radiation, strong acids/bases, or organic solvents, leading to loss of biological activity. | | Renaturation | The process by which a denatured protein can regain its native conformation and biological activity under suitable conditions, demonstrating that the primary structure dictates the protein's final form. | | Precipitation | The clumping and settling of protein molecules, often caused by the disruption of their hydration shell by high salt concentrations (salting out) or other agents, which can be reversible if the protein is not denatured. |