(1) Biological Organization, Water, Molecular Interactions, and Acid-Base Chemistry

Cellular Dimensions

• Size of these cells are going to be dependent on how much O2 needs to be transported from the external to internal part of the cell

• ALL cell need O2 for energy

• The size + shape of the cell is going to be dependent on how much O2 you need to get to the diff. compartments within the cell

• Upper limit of cell size is likely set by the rate of transport + need to deliver O2 to all parts of the cell

Structural Features of Animal Cells

• Each organelle enclosed within a lipid bilayer

• Cell has multiple biomolecules that must get from outside of the cell into the cell

• Cell is built on multiple biomolecules

Cells Build Supramolecular Structures

• Monomeric Units → Macromolecules → Supramolecular Complexes

  • Monomeric Units: most basic unit

  • Macromolecules: polymers utilize non-covalent bonds to accurately fold to form macromolecules

• Subunits held together by covalent bonds

• Supramolecules + Macromolecules are held together by large number of weaker interactions

  • Noncovalent interactions (hydrogen bonds)

  • Ionic interactions, van der Waals interactions, hydrophobic effect

Biomolecules

• Carbon = Major Component

• Chemistry of living things are organized around the properties and interactions of carbon

  • These bonds will determine the characteristic of the molecule that is formed

Geometry of Carbon Bonding

• The lightest elements form the strongest bonds

• Carbon can form covalent bonds w/ up to 4 other carbons to build linear and branched chain

  • Tetrahedral

  • Single C-C bond = flexible + can rotate b/t each molecule

  • C=C is very fixed

    • Planar = can both have cis + trans config.

• Carbon can form single bonds w/ hydrogen, sulfur, and phosphorus

  • Can form single and double bonds w/ oxygen and nitrogen

• When carbon interacts w/ something that is more electronegative, then there’s going to be a dipole

Functional Groups of Biomolecules

• Biomolecules = FGs attached to carbon

• FGs important in determining the chemistry / personality of protein

• Acetyl-coenzyme A → important for respiration + lipid oxidation + lipid synthesis

Molecular Composition of Human Cells

• # Molecules = use Avogadro’s number

• Molecule % = highest % of the cell is water

• Shape of the cell will depend on the requirement of diffusion of O2 as well as these biomolecules

  • Biomolecules restricted to stay within the cell by being phosphorylated

Limits on Cell Size

• Lower Limit = size of required biomolecules

• Upper Size = rate of solute molecular diffusion in an aqueous environment

Four Major Classes of Biological Macromolecules

1. Nucleic Acids, e.g. DNA

   • Store & transmit info.

2. Proteins, e.g. hemoglobin

   • Structure & catalysis

3. Lipids, e.g. phosphatidylcholine

   • Membranes & energy storage

     • Convert carbon-based molecules to energy

4. Polysaccharides, e.g. bacterial surface

   • Energy storage, structure, surface recognition

     • Carbohydrates form cellulose in plants

Building Blocks of Biochemistry

• All cellular activity are the foundation of life

• These building blocks are used to build polymers

• These polymers fold into their appropriate conformation, and when they fold, they’re going to use non-covalent bonds to build the supramolecular structures

• Parent Sugar = alpha-D-Glucose

Bioenergetics, Thermodynamics & Metabolism

• Gibbs Free Energy, G: amount of energy in a rxn at constant temp. and pressure

  • Required to do work

• Enthalpy, H: heat of a rxn reflecting the # and kind of chemical bonds in reactants and products

  • Heat energy ABSORBED = endothermic

  • Heart RELEASED = exothermic

    • Usually spontaneous

• Entropy, S: randomness or disorder in a system

  • Positive = increasing randomness

• Spontaneous rxns occur when ΔG is negative

  • Or when ΔH is highly negative, exothermic

• Reaction 1: if the product is still above the original energy of the starting product, ΔG is positive

• Reaction 2: if the product is below the energy of starting product, ΔG is negative

• Reaction 3: coupled rxn → ΔG is positive and it need energy

Coupling Reactions

• Energy-requiring (endergonic) rxns are often coupled to rxns that release free energy (exergonic)

• Breakage of phospho-anhydride bonds in ATP = Highly Exergonic

Structure of ATP

ΔG° = -RTlnK_eq

• K_eq and ΔG° are measures of a reaction’s tendency to proceed Spontaneously

Genetic Principles

• The structure of DNA allows its replication and repair w/ near-perfect fidelity

• Dexyribonucleotides (DNA) = monomeric subunit that make up the DNA polymer

  • The central dogma of pretty much every cell is the nucleic acid

• Each DNA NATIVE conformation = precise 3-D structure of protein

  • Crucial to protein function

  • Ribonucleotide in one strand pairs specifically w/ a complementary DNA in opposite strand

  • Strands are held together by hydrogen bonds

Changes in Hereditary allow Diversity

• Native Conformation = precise 3D structure of a protein

  • Crucial to protein function

• Mutation = changes in the nucleotide sequence of DNA

  • Changes the instructions for a cellular component

  • Can be beneficial

• Wild Type = unmutated cells

  • Original state of your protein

Water

• Most intermediates of metabolites, nucleic acids, and proteins are soluble in water

• Lipid bilayers form spontaneously in water + stabilized by their interaction w/ it

• Ionization Behavior of Water → Weak acids and bases dissolved in water can be represented by one or more equilibrium constants

• Buffer = aqueous solution of a weak acid + its salt

  • Resists changes in pH

• Hydrogen Bonds, Ionic Interactions, and Hydrophobic Effect = individually weak

  • Combined effect influence the 3D shape and stability of biological molecules and structures

Structure of Water & Hydrogen Bonding

• Dipolar Nature of Water

  • Hydrogen atoms = Localized partial positive charged

  • Oxygen atom = Partial negative charge

• Tetrahedral Arrangement

  • Electron pairs and hydrogen atoms around oxygen atoms

• Hydrogen Bonds

  • Longer and weaker than covalent O-H bond

Hydrogen Bonding in Water

• 4 hydrogen bonds possible per water molecule

• Entropy Effect: important for clathrate-like structure

• Lifetime of Hydrogen Bond: liquid water can be described as a flickering structure

• Water typically form these cage-like structures, especially around non-hydrophobic molecules

Thermodynamics of Water

• Melting or Evaporation

  • Require heat from environment

  • Entropy of the aqueous system increase (+ΔH)

• Room Temp. = Melting and evaporation occur spontaneously

  • ΔG must be negative

  • Because ΔH is positive

  • Increase in ΔS drives these changes

Hydrogen Bonds in Biochemistry

• Hydrogen bond donors

  • N-H

  • O-H

  • NOT C-H

    • Will NOT have hydrogen bonds b/t carbon and carbon → carbon share abt. the same electronegativity

• Hydrogen bond acceptors (N: and O:)

• Hydrogen bonds will form b/t a molecule that is more electronegative

Examples of Hydrogen Bonding b/t Molecules: Alcohol and Water

Water as the hydrogen bond acceptor

Examples of Hydrogen Bonding b/t Molecules: Ketone and Water

Water as the hydrogen bond donor

Hydrogen Bonds are Directional

• Hydrogen bonding is stronger when 3 atoms involved lie in a line

• At an angle → Weaker hydrogen bond

Weak Noncovalent Interactions

• Hydrophobic Interactions

  • Displacement of water

  • Largely formed by dipole b/t 2 hydrophobic molecules

• Pi Stacking

  • Aromatic ring stacking

  • Regions of opposite changes (polarity)

• Van der Waals Interactions

  • Weak but many

  • Based on the fact that molecules have multiple dipoles

• Hydrogen Bond

• Electrostatic

  • Opposites attract, like repel

• Salt Bridge (Hydrogen Bonding + Electrostatic)

  • Carboxylate amino side-chain (Asp, Glu) to basic amino side-chain (Arg, Lys)

  • Specifically b/t charged residues, NOT based on dipole, hydrogen bonding, or hydrophobic interaction

Amphipathic Compounds in Aqueous Solution

• Amphipathic

  • Both hydrophilic (likes water, polar / charged) and hydrophobic (dislikes water, nonpolar)

• Long-chain Fatty Acids

  • Hydrophobic alkyl chains surrounded by layer of highly ordered water molecules

Free Energy for Dissolving Non-Polar Molecule in Water

• Unfavorable

  • ΔH = positive

  • ΔS = negative

    • You’re going from a high entropy state to low energy state

  • ΔG = positive (unfavorable)

Dispersion of Lipids in H2O

• Each lipid molecule forces surrounding H2O molecules to become highly ordered

• Amphipathic molecules will typically come together to form these solid structures

Clusters of Lipid Molecules

• Only lipid portions at edge of cluster force the ordering of water

• Fewer H2O molecules are ordered

• Entropy increase

Micelles

• All hydrophobic groups are sequestered from water

• Ordered shell of H2O molecules is minimized

• Entropy increased

• Amphipathic molecules will typically aggregate to form micelles in water

  • Clustering together in micelles → Fatty acid molecules reduce hydrophobic surface area exposed to water

  • Fewer water molecules required to form shell of ordered water around hydrophobic surface

• Energy gained by freeing immobilized water molecules stabilizes the micelle

  • Entropy Increase

• Many amphipathic molecules stabilized by hydrophobic effects

• Dispersion of Lipids in H2O

• Clusters of Lipid Molecules

• Micelles

Effect of Water on Enzyme-Substrate Interactions

• Typically, the water molecules around the substrate will disperse and facilitate the formation of hydrogen bonding of substrate and enzyme

  • Favorable b/c water molecule will coat whatever molecule

• Enzyme-substrate interactions stabilized by hydrogen-bonding, ionic, and hydrophobic interactions

Cumulative Effect of Weak Interactions

• Macromolecules

  • Most stable structure usually maximizes weak interactions

• H2O molecules often bind tightly to biomolecules that they are part of crystal structure

Water is Partially Ionized

• H2O molecules → Slight tendency to undergo reversible ionization to yield hydrogen ion (a proton) and a hydroxide ion

• Hydrogen ions are immediately hydrated to form hydronium ions (H3O+)

  • These