Biochem L1 & 2-Amino Acids & Proteins chemistry -sem 241.pdf

PHYSL215 Block SEM 241- 2024/2025 Amino acids & Protein chemistry Definition of amino acids Classification of amino acids (polarity-metabolic-nutritional) Properties of amino acids  Amino Acids are the building blocks of proteins ONLY 20 amino acids (out...

PHYSL215 Block SEM 241- 2024/2025 Amino acids & Protein chemistry Definition of amino acids Classification of amino acids (polarity-metabolic-nutritional) Properties of amino acids  Amino Acids are the building blocks of proteins ONLY 20 amino acids (out of 500 in nature) are present in human body (that are coded for by DNA) Amino acid is an organic acid which contains both an acidic carboxyl group (-COOH) and a basic amino group (-NH2) and Unique side chain (R group) distinguishes one amino acid from another. In most natural amino acids, the amino group is attached to the a-carbon atom i.e. the carbon atom adjacent to the carboxyl group So, they are called a amino acids General Structure of amino acids  I- Polar or non polar Classification of amino acids according to side chains properties (R) In proteins: almost all of these carboxyl & amino groups are combined in peptide bond Carboxyl & amino groups of peptide bond do not share in chemical reactions of amino acids So, it is the nature of the side chains that determines the role of an amino acid in a protein. Accordingly, amino acids are classified according to properties of their side chains i.e. whether they are polar or nonpolar 1- Hydrophobic (nonpolar) : Side chains are insoluble in water, not form H or ionic bonds 2- Uncharged hydrophilic (polar) : form hydrogen bonds 3- Charged hydrophilic (polar) : form ionic and hydrogen bonds Location of nonpolar amino acids in proteins: in proteins found in aqueous solutions (a polar environment), the side chains of the nonpolar amino acids tend to cluster together in the interior of the protein. II- III-  Properties of amino acids 1- Optical activity of amino acids - The α-carbon of each amino acid is attached to four different chemical groups. So, they can exist in two forms called as D & L that are mirror images of each other - The two forms in each pair are termed optical isomers - All amino acids found in proteins are of the L-α -amino acids - D-amino acids are found in some antibiotics, plant & bacterial cell walls 2- The isoelectric point (pI): - At certain pH, an amino acid form Zwitterion (dipolar ions) i.e. an ion carrying both equal negative & positive charge & hence, is electrically neutral. So, it will not migrate to cathode or anode. - - The pH at which a zwitterion is formed is called isoelectric point Each amino acid has its own isoelectric point Protein Chemistry Definition of Proteins Biological importance of Proteins Structure of Proteins Denaturation of Proteins Protein misfolding Properties of Proteins Classification of Proteins  Structure of protein 1. Primary structure is linear sequence. 2. Secondary structure is α-helix and β-pleated sheets. 3. Tertiary structure is a final, stable, folded structure, including super secondary motifs. 4. Quaternary structure is functional association of two or more subunits. 1- Primary structure Definition: is the assembly of amino acids in a polypeptide chain linked together covalently by peptide bonds.. It includes number, types and sequence of these amino acids. Peptide bonds: (Primary bond of proteins) 1- formed by a linkage between α-carboxyl group of one amino acid and the α-amino group of adjacent amino acid 2- They are broken by enzymatic hydrolysis ( e.g Digestive proteolytic enzymes) 3- They are not lost by denaturation Polypeptide chain: is a chain formed from joining of amino acids by peptide bonds leaving two free ends : the amino terminal or N-terminal (with free amino group) and a carboxyl terminal , C-terminal (with a free carboxyl group). The sequence of a polypeptide chain starts from the amino terminal 2- Secondary structure Definition: the arrangement of amino acids in the linear sequence (polypeptide) Examples of these arrangements: α helix, β-sheet α-helix: - A spiral structure - Each turn of α-helix contains 3-4 amino acids - Helix is stabilized by hydrogen bonds. β-sheet Composed of segments of fully extended polypeptide chains joined with hydrogen bonding perpendicular to polypeptide backbone 3-Tertiary structure Definition:- The functional and three dimensional structural unit of a polypeptide. Final folding (Packing) of motifs and the final arrangement of domains in a polypeptide Tertiary structure is stabilized by: 1- Disulfide bonds: between –SH groups of two cysteine amino acids 2- Hydrophobic interactions: between amino acids with nonpolar side chains 3- Hydrogen bonds: between hydrogen and electronegative atoms 4- Ionic interactions: between COO- of aspartate or glutamate with –NH3+ of lysine Monomeric proteins: Proteins consists of only one polypeptide chain (subunit) (as for example Myoglobin) = tertiary level only  4- Quaternary structure Definition: The arrangements of more than one polypeptide subunit in a protein is called quaternary structure of protein - Polymeric proteins (dimeric, trimeric or tetrameric, etc): Proteins contain more than one polypeptide chain (subunits) example (Hemoglobin which is tetrameric) Subunits are held together by noncovalent interactions (as hydrogen, ionic bonds) Subunits may work cooperatively with each other (as in hemoglobin) or work independently of each other.  Protein misfolding Causes of protein mis-folding Alzheimer’s Deposits of amyloid beta Spontaneous. and tau disease Gene mutation →an altered protein. Abnormal proteolytic cleavage Type II diabetes Deposits of amylin Effects of protein mis-folding Parkinson’s Deposits of alpha synuclein. Accumulation of insoluble aggregates of disease misfolded protein. The misfolded protein may be degraded. Protein mis-folding diseases - Deposition of misfolded proteins → insoluble aggregates within the cell.  Denaturation of proteins Definition: It is unfolding of protein (loss of protein conformation) by the destruction of all the secondary bonds with loss of the secondary and tertiary structures (also quaternary if present) of protein molecule without loss of the primary structure (peptide bonds ) Effects of denaturation of proteins: 1-Loss of biological activities of proteins 2- Permanent disorder (irreversible) in common cases. 3- Heating of raw meat to increase its digestibility Denaturation can be produced by denaturating Factors: 1-Physical Factors: as heat, ultraviolet rays, X rays… etc 2-Chemical Factors: as strong acids, alkalies, heavy metals Applications of denaturation 70% alcohol solution is used as a disinfectant on the skin (denature the proteins inside the bacteria) Acidic gastric juices cause the denaturation of dietary protein (that helps protein digestion) Medical instruments are sterilized by heating (denature the proteins inside the bacteria)  Properties of Proteins 1- Solubility of proteins in water: Most proteins are soluble in water and insoluble in nonpolar fat solvents. Scleroproteins are insoluble in water. 2- Amphoteric properties of proteins: Proteins contain free carboxyl and amino groups at the ends of the peptide chains. This makes proteins react with acids and alkalies (i.e. amphoteric) Plasma proteins are amphoteric in nature. So they can buffer an acid or base in blood. It helps to maintain acid-base balance of blood and body fluid. The greatest buffering capacity at physiologic pH is provided by histidine. 1- Simple proteins (examples) On hydrolysis, simple proteins yield amino acids only. Albumin & globulins - In blood they are two of the plasma proteins. Histones - A basic protein as it is rich in histidine and lysine. - Available with nucleic acids in chromosomes and in the globin part of hemoglobin. Scleroproteins -They are the most resistant proteins to any solvents (water insoluble). -They form the protective and supportive proteins of the body include: 1-Collagen in tendons, cartilage, bones and connective tissue. 2- Elastin in elastic fibers in lung and big arteries 3- Reticulin in reticular connective tissues of liver, spleen and kidney 4- Keratin in hair, nails and skin (rich in cystiene and cystine)  2- Conjugated proteins (examples) These proteins on hydrolysis give amino acids and non protein parts called the prosthetic groups Phosphoproteins: Proteins that are combined with phosphoric acid Example: milk protein casein Glycoprotein: They consists of proteins + mucopolysaccharides (carbohydrates) They occur in mucous secretions, cartilage, bone & connective tissues. Examples: Receptors, immunoglobulins, mucin in stomach Chromoproteins: As hemoglobin in blood and myoglobin of muscles Hemoglobin & myoglobin are composed of protein part (globin) & non protein red colored part (heme). Lipoproteins: Lipoproteins are conjugated proteins containing proteins & lipids. Plasma lipoproteins transport lipids in blood and cell membranes. Nucleoproteins: They are composed of basic proteins and DNA (chromosomes) and cytoplasmic protein with rRNA (Ribosomes).