MOUDLE 4: PROTEINS AND ENZYMES

• VARIOUS FUNCTIONS OF PROTEINS:

  • Transport of small molecules or ions
  • Structural framework
  • Muscle contraction
  • Immune response
  • Blood clotting
  • Biological Catalysis
• Proteins as Building Blocks:

  Amino Acids is the basic unit of protein connected via polypeptide bond
• Proteins came from the greek word, “proteios” meaning “of first importance”. It composes 50% of the dry weight of the human body. The Recommended Dietary Intake or RDI for adults is 0.8 grams of protein per kg of body weight
• Amino acids contain two functional groups:

  an amino group (NH2 ) and carboxyl group (COOH
• The R group is called the side chain, determines the identity of the amino acid.
• If R is an additional COOH group, it is an acidic amino acid.
• If R is a basic N atom, it is a basic amino acid
• • Glycine is the simplest amino acid
  • All amino acids have common names, which are abbreviated by a 3- or 1-letter designation.
  • 20 amino acids occur naturally in proteins.
  • Humans can synthesize only 10 of the 20 amino acids needed for proteins.
  • The remaining 10, called essential amino acids, must be obtained from the diet and consumed on a regular, almost daily basis
• Essential Amino Acids:

  • standard amino acids needed for protein synthesis that must be obtained from dietary sources because the human body cannot synthesize in adequate amounts from other substances
  • Isoleucine, Leucine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine, Arginine, Histidine, and Lysine
• All amino acids (except glycine) have a chirality center on the α-carbon. L amino acids have the –NH3+ group on the left. D amino acids have the –NH3+ group on the right.
• Amino acids NEVER exist in neutral form. They exist as ZWITTERION (“double ion”)
• Proton transfer from the acid to the base and produces a salt
• ZWITTERION is a molecule that has a positive charge and a negative charge but has no net charge
• PEPTIDES

  • short chains of amino acids joined together by peptide bonds
  • PEPTIDE BOND = AMIDE BOND
• Enkephalins are pentapeptides made in the brain and act as pain killers and sedatives by binding to pain receptors
• Enkephalins are addictive drugs morphine and heroin bind to these same pain receptors, thus producing a similar physiological response, though longer lasting.
• Endorphins are known for their pain reducing and mood enhancing effects
• Oxytocin and vasopressin are cyclic peptide hormones, which have identical sequences except for two amino acids
• Vasopressin aka Antidiuretic Hormone (ADH) targets the kidneys and helps to limit urine production to keep body fluids up during dehydration. It also decreases the volume of urine by increasing the reabsorption of water in the kidneys
• Oxytocin stimulates the contraction of uterine muscles, and signals for milk production; it is often used to induce labor
• The primary structure of a protein is the sequence of amino acids joined by peptide bonds. All bond angles are 120°, giving the protein a zigzag arrangement
• SECONDARY STRUCTURE are 3-D arrangement of localized regions of a protein. These regions arise due to hydrogen bonding between the N—H group of one amide with the C═O group of another. Two stable arrangemen ts are the α-helix and the β-pleated sheet
• α-helix - Intramolecular hydrogen bonding forms within the polypeptide chain to create a spiral structure
• β-pleated sheet are formed by linking two or more β-strands by intermolecular hydrogen bond
• In α-Helix, Amino acids exist in the right handed coiled rod-like structure. 3 to 6 amino acids residues are winded to form an α-helix polypeptide. this structure can be a single chain polypeptide. Alkyl groups of α-helix are oriented outside of the helix
• In β-Pleated Sheet, amino acids exist in an almost entirely extended conformation linear or sheet-like structure. 3 to 10 amino acids are combined to form a β-strand polypeptide. β-Sheet cannot be in a single chain Polypeptide and there must be two or more β-strands. Alkyl groups are oriented both inside and outside of the sheet.
• Shorthand symbols, called ribbon diagrams, are used to indicate these regions of secondary structure Most proteins have regions of α-helix and β-pleated sheet, as well as regions that cannot be characterized.
• The quaternary structure of the protein is the shape adopted when two or more folded polypeptide chains come together into one complex. Insulin consists of two separate polypeptide chains linked by intermolecular disulfide bonds. Hemoglobin consists of four subunits held together by intermolecular forces into a compact 3-D shape
• α-Keratins

  • Proteins found in hair, hooves, nails, skin, and wool.
  • They are composed of long sections of α-helix units, having large numbers of alanine and leucine.
  • These coils wind around other coils making larger and stronger structures (like hair).
  • Two keratin helices coil around each other forming supercoil or superhelix.
• The most abundant protein in vertebrates and found in connective tissues such as bones, cartilage, tendons, teeth and blood vessels. Glycine and Proline account for large fraction of its amino acid residues. Collagen requires three chains in a superhelix. Vitamin C helps stabilize the chains, and, when missing, poorly formed collagen fibers result
• Hemoglobin (Hgb)

  • transports oxygen via blood.
  • It is a conjugated protein (protein + non-protein part)
  • Its non-protein part is called HEME, a complex organic compound containing Fe2+ ion complex with large nitrogen-containing ring system
  • It consists of four polypeptide chains (two alpha subunits and two beta subunits).
• Myoglobin is also a conjugated protein. Its non-protein part is also heme. It stores oxygen in tissues. It also has 153 amino acid residues in a single polypeptide chain and 8 separate alpha-helical sections.
• Carbon monoxide (CO) is poisonous because it binds 200 times more strongly to the Fe 2+ than does O2 . Hemoglobin complexed with CO cannot carry O2 , and cells will die from lack of O2
• Hemoglobin & Myoglobin

  • Sickle cell anemia is a disease where a single amino acid is different in two of the subunits of hemoglobin
  • Red blood cells containing these mutated hemoglobin units become elongated and crescent (sickle) shaped
  • These red blood cells will rupture capillaries, causing pain and inflammation, leading to organ damage, and eventually a painful death.
• Denaturation is the process of altering the shape of a protein without breaking the amide bonds that form the primary structure
• Denaturation often makes globular proteins less water soluble. High temperature, acid, base, and even agitation can disrupt the non-covalent interactions that hold a protein in a specific shape.
• Hydrolysis of the amide bonds in a protein forms the individual amino acids of the primary structure. In the body, the enzyme pepsin in gastric juice cleaves some of the peptide bonds of large proteins to make smaller peptide chains. In the intestines, enzymes trypsin and chymotrypsin hydrolyze the remainder of the amide bond resulting in individual amino acids.
• Catalysis is the process of increasing the rate of a chemical reaction through a catalyst
• Enzymes are proteins that serve as biological catalysts for reactions in all living organisms. They are Water-soluble and Globular proteins
• Active Site is a small cavity that contains AA that are attracted to the substrate with various types of intermolecular forces