UNIT- 3 (MID TERM).pdf

AMINO ACIDS- Amino acids are the building blocks of proteins and play a vital role in biological processes. Structurally, they consist of a central carbon atom (called the alpha carbon), which is bonded to four distinct groups: 1. Amino Group (-NH₂): This functional group contains nit...

AMINO ACIDS- Amino acids are the building blocks of proteins and play a vital role in biological processes. Structurally, they consist of a central carbon atom (called the alpha carbon), which is bonded to four distinct groups: 1. Amino Group (-NH₂): This functional group contains nitrogen and is basic in nature, giving amino acids their name. 2. Carboxyl Group (-COOH): This is an acidic group, consisting of a carbon atom double-bonded to an oxygen atom and single-bonded to a hydroxyl group (OH). It can donate a proton (H⁺) in solution, making amino acids amphoteric (acting as both acids and bases). 3. Hydrogen Atom (H): A single hydrogen atom is bonded to the central alpha carbon. 4. R Group (Side Chain): The R group (or side chain) is unique to each amino acid and determines its specific properties. There are 20 standard amino acids, and the structure of their R groups varies, ranging from a single hydrogen atom in glycine to more complex structures like the indole ring in tryptophan. Classes of Amino Acids Amino acids can be grouped into different categories based on the properties of their side chains: 1. Nonpolar (Hydrophobic) Amino Acids: These amino acids have side chains that are nonpolar and do not interact well with water. Examples include glycine, alanine, valine, leucine, and phenylalanine. 2. Polar (Uncharged) Amino Acids: These have polar side chains that can form hydrogen bonds with water but do not carry a charge at physiological pH. Examples include serine, threonine, and glutamine. 3. Charged Amino Acids: These can be either positively or negatively charged. Positively charged (basic) amino acids, such as lysine, arginine, and histidine, have side chains that accept protons. Negatively charged (acidic) amino acids, such as aspartate and glutamate, have side chains that can donate protons. Zwitterions and Ionization In aqueous solutions, amino acids typically exist in a zwitterionic form, where both the amino and carboxyl groups are ionized. The amino group is protonated (-NH₃⁺), while the carboxyl group is deprotonated (-COO⁻). This gives the amino acid no net charge at its isoelectric point, which varies for each amino acid depending on the R group. The ionization state of amino acids can change with pH. At low pH (acidic conditions), the amino acid carries a positive charge because the amino group is protonated, and the carboxyl group remains protonated. At high pH (basic conditions), the carboxyl group is deprotonated, and the amino acid carries a negative charge. Peptide Bond Formation Amino acids link together through peptide bonds to form proteins. A peptide bond is formed in a dehydration synthesis reaction between the carboxyl group of one amino acid and the amino group of another. The result is a covalent bond that links the amino acids in a polypeptide chain. This chain then folds into specific structures to form proteins with distinct functions, influenced by the properties of the side chains. Biological Importance Amino acids are not only fundamental in protein synthesis but also play roles in metabolic pathways, neurotransmitter functions, and other cellular activities. For example, glutamate acts as a neurotransmitter in the brain, while arginine is a precursor for nitric oxide, a signaling molecule. Understanding the structure of amino acids is crucial for grasping their diverse roles in biology. Their distinct chemical properties, determined by their side chains, allow them to fold into complex structures that form the basis of life’s molecular machinery. Amino acids nomenclature- Amino acid nomenclature is essential for identifying and distinguishing the 20 standard amino acids that are the building blocks of proteins. The naming system is derived from their chemical structures and origins, and there are three main ways to refer to amino acids: common names, three-letter abbreviations, and one-letter codes. The systematic names are based on the rules of organic chemistry, while common names are often based on the source or the discovery of the amino acid. Common Names Each amino acid has a common name, which is typically derived from its source or historical background. For example: Glycine: Named after the Greek word "glykys," meaning sweet, due to its taste. Tyrosine: Named after the Greek word "tyros," meaning cheese, as it was first isolated from cheese. Glutamine: Derived from the word "gluten," as it was first isolated from wheat gluten. These names provide a convenient and widely recognized way to refer to amino acids, even though they don’t directly describe the structure. Three-Letter Abbreviations To simplify the representation of amino acids in biochemical literature, each amino acid has a standardized three-letter abbreviation. This is especially useful when discussing polypeptides or proteins, as it allows for more concise notation. The three-letter codes are usually derived from the amino acid’s common name. For example:  Glycine = Gly Alanine = Ala Leucine = Leu Tryptophan = Trp Some abbreviations are intuitive, like "Val" for valine or "Met" for methionine, while others are less obvious, such as "Asn" for asparagine or "Gln" for glutamine. These three-letter codes are internationally accepted and make communication in biochemistry more efficient. One-Letter Codes In addition to the three-letter abbreviations, amino acids are also represented by a single-letter code. This system was developed by Dr. Margaret Dayhoff in the 1960s to simplify the representation of amino acid sequences, especially for large proteins. The one-letter codes are primarily derived from the initial letter of the amino acid’s name, but some letters are reserved to avoid confusion. For instance: G = Glycine A = Alanine L = Leucine T = Threonine Since some amino acids share the same initial letter, certain letters are assigned based on other features of the amino acid. For example, K is used for lysine (to avoid confusion with leucine), and W is used for tryptophan (because "T" is already taken by threonine). Systematic Nomenclature The systematic names for amino acids are based on the rules of organic chemistry, specifically the IUPAC (International Union of Pure and Applied Chemistry) naming system. These names describe the structure of the amino acid in a more detailed manner, focusing on the functional groups attached to the central (alpha) carbon. For instance, alanine is systematically named 2-aminopropanoic acid, indicating the amino group (-NH₂) is attached to the second carbon of the three-carbon backbone, which is a propanoic acid. Similarly, glycine is called aminoethanoic acid, reflecting its simpler two-carbon structure. While systematic names are precise, they are rarely used in daily biochemical discussions due to their complexity. Chirality and D/L Nomenclature Amino acids, except glycine, are chiral molecules, meaning they have two enantiomers (mirror-image forms). The L- and D- forms (L for "levo" and D for "dextro") refer to the configuration around the alpha carbon. In biological systems, only L-amino acids are used in protein synthesis. For example, L-alanine refers to the biologically active form of alanine. The  D/L nomenclature originates from the similarity of these molecules to D- and L-glyceraldehyde in terms of their optical rotation. Summary Amino acid nomenclature incorporates common names, three-letter abbreviations, and one-letter codes to simplify the representation of these molecules. Systematic names provide structural details but are less frequently used. The D- and L- notation highlights the chirality of amino acids, with the L-form being dominant in nature. Together, these systems ensure clear and efficient communication in biochemistry. general properties of amino acids Amino acids are organic compounds that serve as the building blocks of proteins, playing a central role in biochemistry and physiology. Their general properties arise from their common structure, which includes a central carbon atom (the alpha carbon) bonded to four distinct groups: an amino group (-NH₂), a carboxyl group (-COOH), a hydrogen atom, and a variable side chain (R group). These features impart specific chemical and physical properties to amino acids, making them fundamental to biological processes. 1. Acid-Base Properties Amino acids are amphoteric, meaning they can act as both acids and bases. This is due to the presence of both an acidic carboxyl group (-COOH) and a basic amino group (-NH₂). In solution, amino acids typically exist as zwitterions, where the carboxyl group loses a proton (-COO⁻) and the amino group gains a proton (-NH₃⁺). The overall charge of the amino acid depends on the pH of the environment: At low pH (acidic conditions), the amino acid is protonated and carries a positive charge. At high pH (basic conditions), the carboxyl group is deprotonated, and the amino acid carries a negative charge. At a specific pH (the isoelectric point, pI), the amino acid exists as a neutral zwitterion with no net charge. 2. Chirality Most amino acids (except glycine) are chiral molecules, meaning they have two mirror-image forms called enantiomers: L and D forms. In biological systems, only L-amino acids are incorporated into proteins. This chirality is essential for the specific three-dimensional structure and function of proteins. The L-form of amino acids has the amino group on the left when the molecule is depicted in a Fischer projection. 3. Hydrophilic and Hydrophobic Properties The side chain (R group) of an amino acid largely determines its hydrophilic (water-loving) or hydrophobic (water-repelling) nature:  Hydrophobic amino acids have nonpolar side chains that do not interact well with water. Examples include alanine, valine, and leucine. These amino acids are often found in the interior of proteins, away from the aqueous environment. Hydrophilic amino acids have polar or charged side chains that readily form hydrogen bonds with water. Examples include serine, threonine, and lysine. These amino acids are usually found on the surface of proteins, interacting with the surrounding water or participating in biochemical reactions. 4. Optical Activity Due to their chirality, amino acids (except glycine) can rotate plane-polarized light, a property known as optical activity. L-amino acids, which are predominant in nature, rotate light in a specific direction. This optical property is important for studying protein structures and functions. 5. Peptide Bond Formation Amino acids link together through peptide bonds to form proteins. This bond is formed in a dehydration synthesis reaction between the carboxyl group of one amino acid and the amino group of another, releasing water. The resulting chain of amino acids, called a polypeptide, folds into specific three-dimensional shapes to become functional proteins. 6. Buffering Capacity Due to their ability to donate or accept protons, amino acids can buffer solutions, helping to maintain pH stability. This property is especially important in biological systems, where maintaining a stable pH is crucial for proper enzyme function and metabolic processes. 7. Diversity of Side Chains The variability of the R group gives each amino acid unique chemical properties. Some side chains are small and simple (like in glycine), while others are large and complex (like in tryptophan). This diversity allows proteins to have a wide range of functions, from structural support to enzymatic activity. Conclusion Amino acids possess versatile properties due to their amphoteric nature, chirality, and diverse side chains. These general properties underlie their essential roles in forming proteins and participating in numerous biochemical processes within living organisms. Peptide bond - A peptide bond is a covalent bond that links two amino acids together in a protein or peptide. This bond is fundamental to the structure of proteins, which are polymers composed of long chains of amino acids. The peptide bond is formed through a condensation reaction (also known  as a dehydration synthesis), where the carboxyl group (-COOH) of one amino acid reacts with the amino group (-NH₂) of another, releasing a molecule of water (H₂O) and creating a bond between the two amino acids. Formation of the Peptide Bond The process begins when the carboxyl group (-COOH) of one amino acid interacts with the amino group (-NH₂) of another. During this interaction, a hydroxyl group (-OH) from the carboxyl group and a hydrogen atom (H) from the amino group are removed, combining to form water (H₂O). This reaction results in the formation of a peptide bond, which has the structure (-C(=O)-NH-). This bond is quite stable and resistant to hydrolysis, which is essential for maintaining the integrity of proteins in biological systems. The newly formed peptide bond links the nitrogen of the amino group to the carbonyl carbon of the carboxyl group, creating a dipeptide. Further addition of amino acids leads to the formation of longer chains called polypeptides, which are the primary structures of proteins. Characteristics of the Peptide Bond 1. Planar and Rigid Structure: The peptide bond has partial double-bond character due to resonance between the carbonyl oxygen and the nitrogen of the amino group. This resonance gives the peptide bond a planar and rigid structure, restricting rotation around the bond. As a result, the six atoms involved in the peptide bond (the alpha carbon, carbonyl carbon, carbonyl oxygen, nitrogen, and two alpha carbon hydrogens) lie in the same plane. This rigidity contributes to the overall structure of proteins by limiting the ways in which polypeptide chains can fold. 2. Trans Configuration: The atoms in a peptide bond typically adopt a trans configuration, where the alpha carbons of adjacent amino acids are positioned on opposite sides of the peptide bond. This arrangement minimizes steric hindrance between the side chains of the amino acids. In rare cases, particularly with the amino acid proline, the cis configuration may occur. 3. Stability: Peptide bonds are chemically stable under physiological conditions, meaning they are not easily broken without the assistance of enzymes. In the body, specific enzymes called proteases are responsible for catalyzing the hydrolysis of peptide bonds, allowing for the breakdown of proteins during digestion or other cellular processes. Peptide Bond in Protein Structure The formation of peptide bonds between amino acids is crucial for building the primary structure of proteins, which is the linear sequence of amino acids in a polypeptide chain. The sequence of amino acids and the formation of peptide bonds determine the protein’s overall structure and function. Proteins can consist of hundreds or even thousands of amino acids, linked by peptide bonds, and their complex three-dimensional shapes arise due to the folding and interaction of these polypeptide chains. Hydrolysis of Peptide Bonds  While peptide bonds are stable under normal physiological conditions, they can be hydrolyzed (broken down) under specific conditions, such as in the presence of strong acids or bases, or with the help of enzymes like peptidases or proteases. This process is important in digestion, where dietary proteins are broken down into individual amino acids that can be absorbed and used by the body. Biological Significance Peptide bonds are the backbone of protein structure and are vital for all biological functions that involve proteins, including enzymatic catalysis, cell signaling, immune response, and structural integrity. Proteins owe their stability, function, and diverse roles in living organisms to the formation and maintenance of peptide bonds. In summary, the peptide bond is a fundamental chemical bond that connects amino acids, forming the building blocks of proteins. Its stability, rigidity, and planarity are crucial for the overall structure and function of proteins, playing a key role in nearly every biological process. Essential and Non Essential Amino Acid With Examples- Amino acids, the building blocks of proteins, are categorized into two main types based on whether the human body can synthesize them: essential amino acids and non-essential amino acids. This classification is important because it informs nutritional needs and dietary requirements. Essential Amino Acids Essential amino acids are those that cannot be synthesized by the human body in sufficient quantities, so they must be obtained from the diet. These amino acids are crucial for normal growth, tissue repair, enzyme production, and many other vital biological processes. There are 9 essential amino acids: 1. Histidine: Plays a role in the production of histamine, a neurotransmitter involved in immune responses and sleep regulation. 2. Isoleucine: Important for muscle metabolism, energy regulation, and immune function. 3. Leucine: Promotes muscle growth and repair and plays a role in regulating blood sugar levels. 4. Lysine: Involved in protein synthesis, calcium absorption, and hormone production. 5. Methionine: A precursor to cysteine and important for tissue growth, metabolism, and detoxification. 6. Phenylalanine: A precursor to neurotransmitters like dopamine, epinephrine, and norepinephrine. 7. Threonine: Important for the formation of collagen and elastin, which are key structural proteins in skin and connective tissues. 8. Tryptophan: A precursor to serotonin, which is crucial for mood regulation and sleep.  9. Valine: Plays a role in muscle repair and energy production, especially during physical activity. These amino acids must be consumed through foods rich in protein, such as meat, eggs, dairy products, soy, quinoa, and legumes. Non-Essential Amino Acids Non-essential amino acids can be synthesized by the body from other compounds, so it is not necessary to obtain them directly from the diet. While they are still crucial for various bodily functions, the body can make these amino acids when needed, provided that there is a sufficient supply of the raw materials. There are 11 non-essential amino acids: 1. Alanine: Plays a role in energy production and the metabolism of glucose. 2. Arginine: Involved in wound healing, immune function, and the production of nitric oxide, which helps dilate blood vessels. 3. Asparagine: Important for protein synthesis and maintaining proper cell function. 4. Aspartic Acid (Aspartate): Participates in the citric acid cycle, a key part of cellular energy production. 5. Cysteine: Essential for the production of antioxidants like glutathione and important for detoxification. 6. Glutamic Acid (Glutamate): Functions as a neurotransmitter and is crucial for cognitive functions like learning and memory. 7. Glutamine: Supports immune function and intestinal health and is a major energy source for cells in the gut. 8. Glycine: Involved in the synthesis of collagen and important for maintaining healthy skin and connective tissue. 9. Proline: Important for the production of collagen, supporting skin, cartilage, and joint health. 10. Serine: Involved in metabolism, cell signaling, and the synthesis of other amino acids. 11. Tyrosine: A precursor to important neurotransmitters like dopamine, epinephrine, and thyroid hormones. Non-essential amino acids can be synthesized from intermediates in various metabolic pathways or from other amino acids, such as glutamate or glycine. Conditionally Essential Amino Acids Some amino acids are classified as conditionally essential because they may become essential under specific circumstances, such as illness, stress, or rapid growth, when the body’s demand exceeds its ability to produce them. Examples of conditionally essential amino acids include: Arginine: Essential during times of rapid growth, illness, or recovery from trauma. Cysteine: Essential when the body’s demand for antioxidant defense is high.  Glutamine: Becomes essential during extreme stress or illness, such as after surgery or during infection. Tyrosine: If phenylalanine levels are low, tyrosine can become essential, as it is synthesized from phenylalanine. Summary Essential amino acids (e.g., leucine, lysine, methionine) must be obtained through the diet because the body cannot synthesize them. Non-essential amino acids (e.g., alanine, glutamate, serine) are synthesized by the body and do not need to come directly from dietary sources. Some amino acids become conditionally essential in situations where the body's production cannot meet increased demands. Understanding the difference between essential and non-essential amino acids is important for maintaining a balanced diet, especially for those following vegetarian or vegan diets, as some plant-based foods may lack certain essential amino acids. Protein Primary structure, Secondary structure, Tertiary structure, Quaternary Structure of protein, Ramachandran diagram, Protein stability.- Proteins are complex macromolecules that perform a wide range of functions in biological systems. Their structure is hierarchically organized into four levels: primary, secondary, tertiary, and quaternary structures. Understanding each level is key to understanding how proteins function. Additionally, tools like the Ramachandran diagram and concepts like protein stability are critical for studying protein folding and structure. 1. Primary Structure The primary structure of a protein refers to its linear sequence of amino acids. Each protein is made up of amino acids linked together by peptide bonds, forming a polypeptide chain. The sequence of amino acids is determined by the genetic code and dictates the protein’s overall structure and function. Even small changes in the primary structure, such as a single amino acid substitution (e.g., sickle cell anemia caused by the substitution of valine for glutamic acid in hemoglobin), can have significant effects on a protein's activity and function. 2. Secondary Structure The secondary structure of a protein refers to the local spatial arrangement of the polypeptide backbone, stabilized by hydrogen bonds between the carbonyl oxygen and amide hydrogen of the peptide backbone. The two most common types of secondary structures are: Alpha-helix (α-helix): A coiled structure where the polypeptide chain twists into a right-handed helix. In this structure, every fourth amino acid forms a hydrogen bond with an amino acid located earlier in the chain, stabilizing the helix.  Beta-pleated sheet (β-sheet): A more extended, sheet-like structure where segments of the polypeptide chain line up next to each other, either in a parallel or antiparallel fashion. Hydrogen bonds form between neighboring strands, creating a stable, sheet-like arrangement. Other less common secondary structures include beta-turns and random coils. These elements combine to give the protein its overall shape in specific regions. 3. Tertiary Structure The tertiary structure refers to the overall three-dimensional folding of a polypeptide chain. This structure results from interactions between the side chains (R groups) of amino acids. Various forces contribute to stabilizing the tertiary structure: Hydrophobic interactions: Nonpolar side chains tend to cluster in the interior of the protein, away from the aqueous environment. Hydrogen bonds: These occur between polar side chains and stabilize the structure. Disulfide bridges: Covalent bonds form between sulfur atoms in cysteine residues, creating loops or links between different parts of the chain. Ionic bonds (salt bridges): Form between positively and negatively charged side chains. Van der Waals forces: Weak interactions that stabilize close-packed regions. The tertiary structure is crucial for the protein's function, as it determines the active sites, binding pockets, and overall shape. 4. Quaternary Structure The quaternary structure applies to proteins that consist of more than one polypeptide chain. These separate chains, called subunits, assemble to form a functional protein complex. The arrangement of these subunits is referred to as the quaternary structure. Examples include hemoglobin, which consists of four subunits (two alpha and two beta chains). Like the tertiary structure, quaternary structures are stabilized by various non-covalent interactions and, in some cases, disulfide bridges. 5. Ramachandran Diagram The Ramachandran diagram is a graphical representation used to visualize the allowed and forbidden regions of dihedral angles (phi φ and psi ψ) in the polypeptide backbone. Since the peptide bond is planar and rigid, the rotations around the α-carbon (Cα) are constrained. The diagram shows which combinations of φ and ψ angles are sterically allowed for amino acids in a protein, highlighting regions where secondary structures like alpha helices and beta sheets are most likely to occur. It helps predict protein folding patterns and assess the quality of experimentally determined protein structures. 6. Protein Stability  Protein stability refers to the ability of a protein to maintain its native structure under physiological conditions. Several factors contribute to a protein’s stability: Hydrophobic effect: The tendency of hydrophobic side chains to cluster in the protein core, away from water, is a major driving force in protein folding. Hydrogen bonds: These stabilize secondary and tertiary structures. Disulfide bonds: Covalent bonds between cysteine residues enhance stability, especially in proteins that function in harsh environments. Electrostatic interactions: Salt bridges between charged side chains can contribute to stability. Van der Waals interactions: These weak interactions between closely packed atoms stabilize the protein’s structure. Proteins can lose their stability and unfold or misfold due to changes in temperature, pH, or chemical denaturants, leading to loss of function. This process is known as denaturation. Proper folding and stability are essential for protein function, and misfolding can lead to diseases such as Alzheimer's or prion diseases. Summary Primary structure: Linear sequence of amino acids. Secondary structure: Local folding patterns like alpha helices and beta sheets. Tertiary structure: Three-dimensional folding due to interactions between side chains. Quaternary structure: Arrangement of multiple polypeptide subunits in a protein complex. Ramachandran diagram: A plot that shows the allowed phi (φ) and psi (ψ) angles in the protein backbone. Protein stability: A balance of forces that maintain a protein’s functional conformation.