Principles of Biological Structure Notes

Principles of Biological Structure

Readings

  • No specific assignment in Stryer for this lecture.
  • Two PDF files posted:
    • Chapters 4 and 5 of Mark’s Basic Medical Biochemistry (Smith, C. et al., 2005).
    • Chapter 4: Basic discussion of water, acids, bases, and buffers in biological systems (review).
    • Chapter 5: Brief overview of essential organic chemistry.

Introduction to Chemistry of Human Cells

  • Introduction to the chemistry of human cells.
  • Types of molecules providing structural basis for cellular function.
  • Basic properties of water as a solvent, and acid-base changes in an aqueous environment.

Abundance of Molecules and Ions

  • Water is the most abundant molecule inside a human cell.
  • Most abundant intracellular small cation: potassium.
  • Intracellular anions: chloride and phosphate (H2PO4^-).
  • Cells are bathed in an aqueous environment in vivo.
  • Cell culture maintains physiological environment by providing extracellular ions:
    • Sodium, calcium, chloride, and bicarbonate.

Carbon-Based Life and Organic Molecules

  • Life on earth is carbon-based; all organic molecules contain carbon.
  • Sugars (e.g., glucose) and fatty acids (e.g., myristate, palmitate) contain carbon, hydrogen, and oxygen.
  • Amino acids also contain nitrogen.
  • Nucleotides contain sugars, nitrogenous bases, and phosphate.
  • Small organic molecules are held together by covalent bonds (sharing electrons).
  • Covalent bonds are strong and broken only during specific chemical reactions.

Macromolecules and Subunits

  • Macromolecules are assembled using small organic molecules as building blocks/subunits.
  • Proteins: covalently-bound chains of amino acids.
  • Polysaccharides: assembled from sugar units.
  • Nucleic acids (DNA and RNA): chains of nucleotides.
  • Physical and functional characteristics are determined by specific subunits.
  • Amino acid sequence determines protein properties.

Hydrolysis

  • Hydrolysis is a common process for breaking down macromolecules into building blocks.
  • Digestive enzymes catalyze hydrolysis of macromolecules.

Molecular Shapes

  • Molecules have different shapes.
  • DNA is usually a double helix.
  • Protein molecules vary greatly in shape/size.
  • Space-filling models: atoms as colored spheres.
  • Ball-and-stick models: depict bonds between atoms.
  • Color codes: White=H, red=O, gray=C, yellow=P, blue=N, and green=S.

Covalent vs. Non-Covalent Bonds/Forces

  • Covalent bonds hold together individual organic molecules.
  • Non-covalent bonds/forces affect interactions between molecules and maintain macromolecules in specific 3D structures.
  • DNA molecule example: nucleotide bases are bound covalently into long chains.
  • Binding of two long strands to each other and their joint formation of a double helix is mediation by hydrogen bonds, which are one type of non-covalent interaction.

Electrostatic Interactions

  • Occur between charged atoms or molecules.
  • Opposite charges attract; similar charges repel.
  • Sodium chloride (table salt): inorganic molecule held together by an ionic bond.
  • In aqueous solution, ionic bonds are weakened; ions are separated and surrounded by water molecules.
  • Electrostatic interactions also occur between charged groups on larger molecules (same macromolecule or between two macromolecules).
  • Example: attraction between DNA (net negative charge) and positively charged proteins (e.g., histones).

Hydrogen Bonds Between Water Molecules

  • In each water (H_2O) molecule, the two H atoms are linked to the O atom by covalent bonds.
  • Covalent bonds are highly polar because O has a stronger attraction for shared electrons.
  • Symbols \delta+ and \delta- indicate partial charge differences.
  • Hydrogen bonds form between a positively charged H from one water molecule and a negatively charged O from a second water molecule.
  • Water is liquid because of the strength of hydrogen bonds.
  • Hydrogen bonds: a special type of polar interaction where an electropositive hydrogen atom is partially shared by two electronegative atoms.
  • Other molecules (e.g., alcohols) containing polar bonds can form hydrogen bonds with water and dissolve readily.

Water as a Solvent

  • Water is good at dissolving polar molecules (e.g., inorganic salts).
  • Water molecules surround each ion: negative O portions attracted to cations (positive); positive H portions attracted to anions (negative).

Hydrogen Bonds in Biological Macromolecules

  • Positively charged hydrogen atoms bound in hydroxyl (–OH) or amino (–NH) bonds interact with negatively charged oxygen or nitrogen atoms.
  • Hydrogen bonds between nucleotide bases provide structural basis for DNA double helix pairing.
  • Important in stabilizing the secondary structure of proteins.

Water's Interaction with Other Molecules

  • Water can form hydrogen bonds with other molecules.
  • Example: hydrogen bond between carboxyl group (-C=O) and amide group (-NH) within proteins.
  • Water molecules break hydrogen bonds and replace them with new bonds to the water molecule, changing macromolecule conformation.

Hydrophobic Effect

  • Unlike -C=O, -N-H, and H-O-H bonds, bonds between carbon and hydrogen atoms are non-polar and do not associate with water molecules.
  • Non-polar molecules (and portions of molecules) are pushed out of the hydrogen-bonded water network (hydrophobic).
  • This causes non-polar molecules to be pushed together.
  • Fats (triacylglycerols/triglycerides) are completely non-polar/hydrophobic.
  • When mixed with water, they separate out (oil and vinegar example).

Amphipathic Molecules

  • Molecules with both hydrophilic and hydrophobic portions aggregate in aqueous solutions.
  • They form structures where non-polar portions are internal and polar portions are associated with the aqueous environment.
  • Cellular membranes are formed by phospholipids (polar head group and two long, non-polar, hydrocarbon chains).
  • Membrane: sandwich with two layers of phospholipids; non-polar chains form the inner part; polar head groups face outwards.

Biological Structure and Water Interactions

  • Biological structures fold to minimize unfavorable interactions with water.
  • Protein molecule example: polar and non-polar side chains.
  • In native protein, non-polar chains are folded into the core; polar groups are on the surface, hydrogen bonding with water or other polar groups.
  • When native folding is disrupted, the protein is denatured and loses function.

Van der Waals Attractions

  • Occur because electrons around nonpolar atoms produce flickering polarization and transiently induce polarization in nearby atoms.
  • Individually weak, but aggregate effect is significant when surfaces are in close contact.
  • van der Waals forces attract atoms to each other until they get too close and are repelled.

Ionization of Water

  • Positively charged hydrogen atoms move from one water molecule to another.
  • Produces hydronium ions (H_3O^+) and hydroxyl ions (OH^-).
  • Process is spontaneous and reversible.
  • Ionization is in equilibrium: [H^+][OH^-] = 10^{-14}.
  • Square brackets denote concentration.
  • Hydronium ion (H_30^+) often written as H^+ for simplicity.

pH Scale

  • When water ionizes, equal numbers of hydronium and hydroxyl ions are formed.
  • Concentration of each is 10^{-7} M.
  • pH scale uses the negative logarithm of the hydronium or hydrogen ion concentration.
  • Pure water has a pH of 7.
  • Acidic substance addition increases hydrogen ion concentration; pH values less than 7.0.
  • Basic/alkaline solutions have [OH^-] > [H_3O^+]; pH values greater than 7.0; hydrogen ion concentrations less than those of acidic solutions.
  • Higher pH means lower hydrogen ion concentration.

pH of Biological Fluids

  • Cytoplasm (cytosol) is essentially neutral.
  • Lysosomes are acid (low pH) compartments for breaking down macromolecules.
  • Stomach acid provides a low pH environment for digestion.

Strong vs. Weak Acids and Bases

  • Strong acids and bases are completely dissociated/ionized in aqueous solutions (e.g., HCl, H2SO4, NaOH).
  • Biologically important acids/bases are “weak” and only partially ionized.
  • Acetic acid is in equilibrium with acetate ion (conjugate base).
  • Acid (HA) + H2O \rightleftharpoons H3O^+ + Conjugate base (A^-)
  • CH3COOH + H2O \rightleftharpoons H3O^+ + CH3COO^-
  • Ammonia is a weak base in equilibrium with ammonium ion (conjugate acid).

Buffering

  • Weak acids and bases can accept or donate hydrogen ions (H^+), aka protons.
  • They can buffer solutions and maintain a relatively constant pH.

Henderson-Hasselbalch Equation

  • Expresses the quantitative equilibrium between an acid and its conjugate base.
  • Usually expressed in negative log form using pKa rather than Ka.
  • When pH = pK_a, concentrations of acid (HA) and conjugate base (A^-) are equal.
  • Under these circumstances, the acid-conjugate base pair has the greatest capacity to accept or donate hydrogen ions, and is most effective as a buffer.

Biological Buffers

  • The carbon dioxide – bicarbonate acid-base couple is an effective buffer of blood pH.
  • Proteins in blood also provide significant buffering capability.
  • Some culture media contain organic buffers (e.g., HEPES) to enhance buffering capacity and decrease dependence on carbon dioxide environment.
  • Inorganic phosphate is a major intracellular buffer.
  • Cell culture media cannot use phosphate buffers because they mimic the higher extracellular concentration of calcium.
  • Calcium ions are necessary for cell adhesion and other functions.
  • In the presence of millimolar concentrations of calcium, the phosphate ions form insoluble calcium phosphate complexes.