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}$$