Introduction to Biochemistry

1
Introduction to Biochemistry

• Why am I here?
• How can the world become a better place?

2
Why study Biochemistry

• The chemistry basics of many important processes
  are now elucidated
• Flow of genetic information conversion of energy
  forms, molecular motors
• Common chemical principles are the bases of all
  life forms
• Genetic information, conversion of energy
• Biochemistry is the basis of medical science and
  technology
• Enzymes, cell growth, protein structure, DNA
  mutations
• Biochemistry is the basis of all advances in
  medical science and technology
• bioengineering, biochemical engineering,
  biomedical engineering, biotechnology, tissue
  engineering, etc.

3
What will this class be like

• Unlike your traditional CHME classes
• Not as much problem solving
• Not as many equations
• Not as much calculator use
• A lot more memorization
• More like your organic chemistry class but way
  more fun and interesting!
• NOT like your P-Chem or Thermo class (but there
  is a lot of P-Chem and Thermo in biochemistry)
• This class will prepare you for future studies in
  advanced topics in Biochemical Engineering (CHME
  474/874, Bioseparations Engineering (CHME
  475/875), Tissue Engineering (TBA), Biomolecular
  Engineering (TBA)

4
Bio-organic Chemistry

• Remember important functional moieties and their
  basic properties (e.g., pKa, etc.)
• Amines, acids, aldehydes, esters, etc.
• Carbohydrates, polymers, etc.
• You will have to memorize this information
• Molecular models
• Text website has numerous molecular structures
  that use Chime, Rasmol, PBD viewer, etc. you
  must understand how to manipulate structures with
  this software.
• Understand ball-stick, space-filled, skeletal,
  how to highlight amino acids, etc.

5
Molecular Dimensions

• Biochemists were the first real
  nanotechnologists all the rest are wannabe
  copycats.
• C-C bond 1.54 Å
• Monosaccharides, amino acids 10 Å
• Proteins 2-8 nm (20-80 Å)
• Macromolecular assemblies viruses, ribosomes,
  phage 10-100 nm
• Cells
• Eukaryotes 1 - 10 microns
• Prokaryotes 0.5 - 2 microns

6
Molecular Interactions - electrostatics

• Biochemistry is ruled by non-covalent
  interactions (although covalent bonds are
  important)
• Electrostatic bonds - Coulombs law
• Important in protein folding, protein
  interactions, protein purification, DNA physical
  properties, etc.
• In biomolecules, r 2.8 Å 3-7 kcal/mol
• Dielectric constant (D, e) plays a major role
• water 78.54 at 25oC
• Methanol 32.63
• Ethanol 24.3
• Cyclohexane 2.02

7
Molecular Interactions H bonding

• Hydrogen bond sharing of a H atom between two
  other atoms (molecular menage a trois) - in
  biochem usually O and N
• Orientation is very important colinear is
  strongest
• Typical H-bond strengths 3-7 kcal/mol (vs. 83
  kcal/mol for C-C bonds)
• Prevalence protein folding, DNA structure,
  enzyme mechanics, etc.

8
Molecular Interactions Van der Waals

• Non-specific attractive forces
• appear when atoms are 3-4Å apart LJ potential
  diagram
• 1 kcal/mol similar to weak induced dipole
  interactions
• Very weak individually, but number of VdW bonds,
  geometry, and steric complimentarity in
  biomolecules make it a major contributor to
  interactions

9
Importance of water

• When looking at the periodic table, the closest
  related compounds to water (H2O) would be H2S or
  maybe H3N (i.e. NH3, or ammonia) or HF
  (hydrofluoric acid).
• It is important to understand the nature of
  hydrogen bonding, particularly between water
  molecules

10
Dipole Oxygen is more electronegative than
hydrogen, therefore, the oxygen-hydrogen bonds
are polar. Due to the bent geometry, the overall
molecule has a dipole.

• Molecular dimensions
• The O-H bond length is 1.0Å (0.1nm)
• The van der Waals distance for hydrogen is 1.2Å
• The van der Waals distance for oxygen is 1.4Å

However, in simple calculations water is often
represented as a sphere with a radius of 1.4Å.
This is because the oxygen will withdraw the
electron cloud from the hydrogen, and thus, the
van der Waals distance of hydrogen is reduced.
11
Water Structure

• Water has a "structure"
• Each water molecule can participate in up to four
  hydrogen bonding interactions
• The two hydrogens are potential "donors" in a
  hydrogen bond interaction
• The two oxygen lone pairs are each potential
  "acceptors" in a hydrogen bond interaction
• Each H-bond is about 23kJ/mol in strength
• As a liquid, neighbor molecules move around and
  H-bonds are constantly breaking and new ones
  reforming
• average lifespan of a single H-bond in water is
  about 10ps
• The combination of so many H-bonds between the
  water molecules results in the unusually high
  boiling point and melting point of water

12
Water structure

• The distance between Oxygen atoms in a typical
  H-bond between water molecules is about 2.8Å
  (0.28nm)
• The O-H covalent bond length is 1.0Å. Therefore
  the H-bond distance between the donor H and the
  acceptor O is typically 1.8Å, but can vary from
  1.6Å to 2.4Å.
• The typical distance of 2.8Å between O atoms in
  adjacent water molecules explains why a 1.4Å
  radius sphere model for waters can be useful
• The orientation is important the O-H bond vector
  points directly at the acceptor lone pair, and
  vice versa

13
Ice

• Cooling reduces thermal energy and you can get a
  phase transition to a solid form of water (i.e.
  "ice")
• A regular (crystalline) H-bond lattice forms (as
  opposed to the transient nature in the liquid
  form). This regular lattice is actually
  less-densely packed than the liquid form. Thus,
  ice floats in liquid water.
• The lattice is a regular arrangement based on the
  near-tetrahedral geometry of the Oxygen
• Six molecules can form a closed H-bond ring in
  ice, resulting in hexagonal appearance of
  snowflakes
• Water molecules in ice have low entropy

14
Water as a polar solvent

• Water molecules will separate, surround and
  disperse a polar solute
• Water molecules surrounding a polar or charged
  solute will orient according to H-bonding or
  electrostatic principles of dipole-dipole
  interactions (i.e. oppositely charged ends of
  dipoles will orient towards each other)
• The water molecules surrounding a solute are
  referred to as the "hydration or solvation shell"
  of waters
• The ability of water molecules to surround and
  separate oppositely charged ion pairs in a
  solution is referred to as the dielectric
  constant of water.
• What this equation says is that if a substance
  can prevent opposite charges from attracting each
  other (i.e. ions in water are "shielded" by the
  solvation shell from other ions) then it has a
  high dielectric (i.e. Attractive force between
  ions is small)
• Water has a dielectric of 78.5, and Hexane has a
  dielectric of 1.9 (will not shield charged ions
  from each other)

15
Hydrophobic Interactions

• Water cannot hydrogen bond with non-polar
  molecules (aliphatic, aromatic hydrocarbons)
• Water will form an ice-like lattice arrangement
  ("clathrate") around non-polar solutes in
  solution.

• This arrangements of water molecules is
  entropically costly.
• Entropic cost will be minimized if the non-polar
  solute adopts a shape with the smallest surface
  area (i.e. a sphere). This is why oil forms a
  sphere in water.
• Remember, nature wants to maximize entropy 2nd
  Law of Thermodynamics

Removing non-polar groups from aqueous solution
frees up water molecules in the clathrate,
increases entropy, and is a lower free energy
condition (i.e. spontaneous). Oil drops in an
aqueous environment will coalesce into a single
large spherical drop (i.e. the "hydrophobic
effect").
16
Amphipathic molecules

• Amphipathic and amphipathic molecules possess
  both polar and nonpolar groups
• "amphi" means both, "pathos" means passion,
  "philos" means loving
• Such molecules have both a polar region and a
  non-polar region
• In aqueous solution they have the ability to self
  organize according to the hydrophobic effect,
  i.e. they will assemble to as to remove the
  non-polar group from solution

All of these properties of water and concepts of
intermolecular interactions of water/solutes are
extremely important in the consideration of
molecular properties of DNA, RNA, proteins,
carbohydrates, lipids, and supramolecular
assemblies
17
Thermodynamics and Kinetics

• First Law total energy of system and
  surroundings is constant
• Second Law total entropy of a system and
  surroundings always increases
• Biochemistry usually only think about system,
  but remember the surroundings
• DG DH TDS lt 0 for spontaneous process.
• Thermodynamics systems at equilibrium
• Kinetics not at equilibrium, rates

18
Acid/Base in Biochem

• Why? pH and pKa can be hugely important in
  biochemical reactions.
• pH, pKa, Henderson-Hasselbalch equation, etc.

19
Genomic sciences

• Sequencing of genomes of humans, E. coli,
  nematodes, fruit flies, etc. has led to an
  explosion in biochemical understanding at all
  levels.
• More on this in CHME 474