Principles of Biological Structure Notes

Principles of Biological Structure

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

Small Molecules in Cells - 1

• Water and small inorganic ions comprise most of the small molecules.
• Major intracellular ions:
  • Potassium (K^+).
  • Chloride (Cl^-).
• 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.

Macromolecules and Their 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.
• 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^+, Cl^-.
  • Charged (ionic) groups on large molecules such as proteins, nucleic acids.

• Opposite Charges Attract

• Like Charges Repel

• Example:

  • Negatively charged group of a substrate interacts with a positively charged group of an enzyme.

Hydrogen Bonds

• Water molecules are polar. This means that 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 Dissolving Charged Molecules

• Water is Good at Dissolving Charged Molecules (such as salt)
• Electrostatic interactions with ions
• Example:
  • Sodium (Na^+) and Chloride (Cl^-) ions interacting with water molecules.

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 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.

Membranes

• 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.

Biological Structures and Water

Biological Structures Fold to Maximize Favorable and Minimize Unfavorable Interactions with Water

• Unfolded (denatured)
• Folded (native)

Van der Waals Interactions

• Short range interactions between molecules.
• Positive attraction between molecules.
• Repulsion of molecules when 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.
• Simplified:
  • H_2O H^+ + OH^-
  • {Keq} = {[H^+][OH^-] \over [H_2O]}
  • 1.8 X 10^{-16} M= 10^{-14} / 55.5 M
• When [H^+] increases, [OH^-] decreases.
• [H^+] x [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) H^+ + Conjugate base (A^−)
• Weak acids and bases are only partially dissociated in aqueous solution.
• Acetic acid (vinegar) is a weak acid:
  • CH3COOH + H2O H3O^+ + CH3COO^−
  • Vinegar has a pH of ~ 3.
• Ammonia (NH3) is a weak base. The conjugate acid is the ammonium ion (NH4^+)
  • NH4^+ H^+ + NH3
  • Household ammonia has a pH of ~ 11.
• Many biologically important molecules are weak acids or bases

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 Ka:

  • Ka = {[H^+][A^-] \over [HA]}
  • Dissociation constant (Ka) for a weak acid. HA = the undissociated acid, A- = the conjugated base.
  • 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 pKa.
  • pH = pKa + log{[A^-] \over [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 = pKa.

Physiological Buffers

• The carbon dioxide-bicarbonate acid-base couple is a major regulator of blood pH. Cell culture media often use CO2 as a buffer:

  • CO2 + H2O H2CO3 (carbonic acid)
  • H2CO3 H^+ + HCO_3^− (bicarbonate)

• Inorganic phosphate is a major regulator of cytosolic pH.

  • H2PO4^- H^+ + HPO_4^{-2}