Principles of Biological Structure - Detailed Notes

Principles of Biological Structure

Basis for Understanding

  • Provide the basis for understanding the structure and function of cells and organisms.
  • Provide the basis for understanding biological specificity.
  • Examples of relationships of function to structure:
    • Enzyme specificity
    • Genetic information
    • Membrane properties

Small Molecules in Cells - 1

  • Water and small inorganic ions comprise most of the small molecules.
  • The major intracellular ions are:
    • potassium (K^+
    • chloride (Cl^-
  • The major extracellular cation (positively charged ion) in biological fluids and culture media is sodium (Na^+

Small Molecules in Cells - 2

  • Cells contain a variety of small organic molecules.
  • These molecules are comprised primarily of carbon (C), hydrogen (H), oxygen (O) and often nitrogen (N) atoms, held together by covalent bonds.

Macromolecules in Cells

  • Macromolecules are built by covalent binding together a series of smaller molecules.
  • Macromolecules of cells:
    • Proteins
    • Nucleic Acids (DNA, RNA)
    • Polysaccharides
    • Lipids
  • Many molecules contain more than one of the above components:
    • Example: Glycoproteins have carbohydrate (sugar) chains attached to the protein.

Hydrolysis of Macromolecules

  • Macromolecules are formed by adding subunits to one end. A molecule of water is removed with each addition or condensation reaction.
  • The reverse reaction – the breakdown of the polymer – occurs by hydrolysis which involves the addition of water.

Macromolecule Shapes

  • DNA forms a double helix.
  • Proteins are found in many shapes and sizes.

Non-covalent Interactions

  • Non-covalent forces affect the interactions between molecules. They also serve to maintain macromolecules in their characteristic shapes.
  • There are several types of non-covalent interactions:
    • Electrostatic (Ionic) Interactions
    • Hydrogen Bonds
    • Hydrophobic Interactions
    • Van der Waals Interactions

Electrostatic (ionic) interactions

  • Occur between charged molecules (ions):
    • Small ions: Na^+, CI^-
    • Charged (ionic) groups on large molecules such as proteins, nucleic acids
  • Opposite Charges Attract
  • Like Charges Repel
  • Example illustrating attraction between negatively charged group of a substrate and positively charged group of an enzyme.

Hydrogen bonds

  • Water molecules are polar; the oxygen atom has a small negative charge due the larger electronegativity and hydrogen atoms have a partial positive charge.
  • Partially positively charged hydrogen atoms are attracted to the negatively charged unshared electron pairs of oxygen.
  • Hydrogen bonds between water molecules are responsible for many of the physical properties of water, including its high melting and boiling points.

Water as a Solvent

  • Water is good at dissolving charged molecules (such as salt).
  • Electrostatic interactions with ions.

Types of Hydrogen Bonds

  • Hydrogen bonds occur between many types of polar groups
  • Hydrogen bonding occurs between groups that contain oxygen or nitrogen with unshared electron pairs and partially positively charged hydrogen:
    • -OH
    • -NH
  • Hydrogen bonds stabilize many biological molecules:
    • DNA
    • proteins

Water's Role in Breaking Hydrogen Bonds

  • Hydrogen bonds often stabilize the folded structure of macromolecules such as proteins.
  • Water can open up and replace these hydrogen bonds.

Hydrophobic Molecules

  • Nonpolar molecules are hydrophobic.
  • Triacylglycerols (fats) are nonpolar molecules with long hydrocarbon chains.
  • Hydrophobic molecules attract each other and dissolve poorly in water.

Membrane Structure

  • Membranes have a hydrophobic interior and a hydrophilic exterior.
  • Phospholipids provide the basic structure of cellular membranes. They have polar (or sometimes charged) head groups and nonpolar tails.

Folding and Interactions with Water

  • Biological Structures Fold to Maximize Favorable and Minimize Unfavorable Interactions with Water
  • Illustrates the transition from unfolded (denatured) to folded (native) states.

Van der Waals Interactions

  • Short range interactions between molecules.
  • Positive attraction between molecules.
  • Repulsion of molecules when they get too close.

Ionization of Water

  • Positively charged hydrogen atoms move readily from one water molecule to another creating hydronium (H_3O^+$) and hydroxyl (OH^−) ions.

  • H_2O
    amelongrightarrow H^+ + OH^-

  • K{eq} = [H^+] [OH^-] / [H2O]
  • 1.8 \times 10^{-16} M = 10^{-14} / 55.5 M
  • When [H^+] increases, [OH^-] decreases.
  • [H^+] \times [OH^-] = 10^{-14}

The pH Scale

  • Pure water: [H^+] = [OH^-] = 10^{-7} M
  • The pH scale reflects logarithmic changes in [H^+]
  • Pure water is neutral, and has a pH of 7.
  • Solutions with higher [H^+] (and lower [OH^-]) are acidic.

pH of Biological Fluids

  • The cytosol is neutral.
  • Lysosomes are acidic.
  • Most culture media are slightly basic, with a pH of 7.2 – 7.4
  • Phenol red is used as an indicator of pH in culture media.
    • Red at pH 7.4
    • Turns yellow with acidity (↓pH)
    • Turns purple with ↑ pH.

Acids and Bases

  • Acid (HA) \rightleftharpoons H+ + Conjugate base (A-)
  • Weak acids and bases are only partially dissociated in aqueous solution.
  • Acetic acid (vinegar) is a weak acid:
    • CH3COOH + H2O \rightleftharpoons H3O^+ + CH3COO^-
    • Vinegar has a pH of ~ 3.
  • Ammonia (NH3) is a weak base. The conjugate acid is the ammonium ion (NH4^+
    • NH4^+ \rightleftharpoons H^+ + NH3
    • Household ammonia has a pH of ~ 11.
  • Many biologically important molecules are weak acids or bases

Buffers

  • Weak acids and bases are buffers
  • There is an equilibrium between an acid and its conjugate base. This means that the pair can either donate or accept protons (H^+
  • Weak acids and bases can thus act as buffers by binding excess H^+ or OH^- ions, and maintain a relatively constant pH, or [H^+]

The Henderson-Hasselbalch Equation

  • Each weak acid has a characteristic dissociation constant or K_a
    • The pKa is the negative log of Ka.
  • A compound is most effective as a buffer when the pH of the solution is within one unit of its pK_a.
  • K_a = [H^+] [A^-] / [HA]
  • Dissociation constant (K_a) for a weak acid. HA = the undissociated acid; A- = the conjugated base.
  • pH = pK_a + log ([A^-] / [HA])
  • Henderson-Hasselbalch equation.
  • pKa, analogous to pH, is the negative log of the dissociation constant Ka.
  • Note that when the concentration of HA and A- are equal, pH = pK_a.

Physiological Buffers

  • The carbon dioxide-bicarbonate acid-base couple is a major regulator of blood pH. Cell culture media often use CO_2 as a buffer:
    • CO2 + H2O \rightleftharpoons H2CO3 (carbonic acid)
    • H2CO3 \rightleftharpoons H^+ + HCO_3^- (bicarbonate)
  • Inorganic phosphate is a major regulator of cytosolic pH.
    • H2PO4^- \rightleftharpoons H^+ + HPO_4^{-2}$$