Foundations of
Biochemistry
Doba Jackson, Ph.D.
Dept. of Chemistry & Biochemistry
Huntingdon College
What distinguishes living organisms
from other forms of matter?
• High degree of chemical complexity
and organization (muscle tissue)
• System for extracting energy from
the environment (bird)
• The ability to self-replicate (zebra)
• Ability to sense changes in the
surroundings and respond
• Defined functions of each
component and regulated
interactions
•
The ability to adapt with time (evolution)
Chemical Foundations
“What are the common chemical
principals important to all cells”
Only 30 of the 90 naturally
occuring elements are found in
biological systems
Components of macromolecules:
the ABC’s of Biochemistry
Proteins
Nucleic Acids
Lipids
Carbohydrates
Biomolecules
are hydrocarbons
You
must remember
all of these
with attached
functionalfunctional
groups!!!!!groups
What do these have in common?
Hydrocarbons
What do these have in common?
All have carbon-oxygen bonds
What do these have in common?
All have carbon-nitrogen bonds
What do these have in common?
All have carbon-sulfur bonds
What do these have in common?
All have carbon-phosphate bonds
Some Definitions
• Chiral center- a carbon atom with four different
a substituents (ie.- asymmetric carbon)
• Enantiomers- pairs of stereoisomers that are
mirror images of each other.
• Diastereomers- pairs of stereoisomers that are
not mirror images of each other.
Enantiomers
4 substituents
Same molecule
3 substituents
Example: 2,3 disubstituted butanes
Stereoisomers distinguisable by
taste
Aspartate
Phenylalanine
Summary of chemical
foundations
• Only 30 of the 90 naturally occuring elements are
found in biological systems
• 99.9% of biomolecules are considered organic
compounds
• Most biomolecules have more than one functional
group
• Conformation, configuration, and constitution are all
important factors for determination of biological
activity
Aqueous Solutions
By Doba D. Jackson, Ph.D.
Dept. of Chemistry & Biochemistry
Huntingdon College
Why study Water
• Water is the most abundant chemical in living
systems making up to 70% of the mass of most
organisms.
• The attractive forces between water molecules and
the slight tendency of water molecules to ionize are of
crucial importance to the structure and function of
biomolecules.
Outline of Discussion
• Weak interactions in aqueous solution
– Hydrogen Bond
– Nonpolar compounds and water insolubility
– Hydrophobic interactions, van Der waals interactions
• Ionization of water, weak acids and bases
– Review acids, bases, Kw and pKa
• Buffers, pH changes in biological systems
– Phosphate, Carbonate buffers in living organisms
– Tris, HEPES buffers commonly used in laboratories
Structure of a water molecule
Less than
109.5º
- The Oxygen bears two partial negative
charges each aligned with the p-orbitals.
- Each Hydrogen bears a positive charge
aligned 104.5º from the OH bond.
The Hydrogen Bond
“I believe that as the methods of Structural
chemistry (x-ray crystallography) are
further applied to physiological problems,
it will be found that the significance of the
hydrogen bond for physiology is greater
than that of any other single structural
feature”
-Linus Pauling, The Nature of the Chemical Bond (1939)
The Hydrogen Bond
- The hydrogen atom becomes between
covalently bound oxygen and the oxygen
aligned from its neighbor.
- The hydrogen bond has a dissociation
energy of 23 kJ/mol (compared to 470
kJ/mol).
- Based on orbital overlap, the hydrogen
bond is 10% covalent and 90%
electrostatic.
- The total hydrogen bond length is
approximately 2.8 Ǻ (~ 3 Ǻ).
Hydrogen bonding in ice
-Solid ice
2 covalent bonds
4 hydrogen bonds
6 total bonds
-Liquid water
2 covalent bonds
2.4 hydrogen bonds
4.4 total bonds
Hydrogen Bonds other than water
Any electronegative atom (usually N, O) with a pair
of electrons can attract a hydrogen attached to another
electronegative atom.
Examples of Biologically
important hydrogen bonds
Alcohol
& water
Ketone
& water
Between amino
acids in proteins
DNA
strands
Water as a solvent
- Polar solutes: compounds that have
polar bonds; usually dissolve
easily in water.
- Nonpolar solutes: compounds that
do not have polar bonds; usually
difficult to dissolve in water but
dissolves easily in nonpolar solvents
(hexane, chloroform or benzene).
- Amphipathic solutes: compounds
with polar and nonpolar groups;
solubility will vary.
What happens to the structure of
water at a hydrophobic interface?
– Water at a hydrophobic surface
loses a hydrogen bond.
– Water molecules compensate for
this by creating a low-density water
network with lower entropy directly
surrounding the hydrophobic solute.
– Water covers the surface with
clathrate-like hexagons, so avoiding
the loss of most of the hydrogen
bonds.
Hydrophobic Effect
Release of ordered water can drive the
formation of an enzyme-substrate
complex
Review weak (noncovalent)
molecular interactions
• Electrostatic (ionic) interactions- The attractive forces
between oppositely charges molecules or functional groups.
• Hydrogen Bonds- an interaction between a hydrogen
covalently attached to an electronegative atom and the electron pair
of another electronegative atom.
• Hydrophobic interactions- the strong tendency of water to
minimize the surface area surrounding nonpolar groups or
molecules.
• Van der Waals forces- are the result of induced electrical
interactions of closely approaching atoms as their negative electron
clouds fluctuate with time.
Van der Waals forces
Weak chemical forces and their
strengths and distances
Strength
(kJ/mol)
strength
Van der Waals forces
Hydrogen bonds
Ionic interactions
Hydrophobic
interactions
Distance
(nm)
.4 – 4.0
12 – 30
.3 - .6
.3
20
<40
.25
>1
Hydrophobic interactions can act across very large
distances which makes these interactions very dominant
in determining macromolecular structure and function
“Proton hopping” common in enzymes that
translocate protons across cell membranes
Cytochrome f; in photosynthesis
Weak interactions are crucial to
macromolecular structure and function
• For macromolecules (DNA, RNA & proteins)
the most stable structure is one that
maximizes the weak bonding possibilities.
Titration curves can reveal dissociation
constants (pKa) and buffer ranges
Henderson-Hasselbalch Equation: relationship
between pH, pKa and buffer concentrations
CH3COO- +
CH3COOH
K
a
H+
CH 3COO    H  

CH 3COOH 
 Log K a   Log
 Log K a   Log
CH 3COO    H  
CH 3COOH 
CH 3COO  
 Log  H  
CH 3COOH 
pK a   Log K a
pH   Log  H  
pK a   Log
CH 3COO  
 pH
CH
COOH
 3

pH  pK a  Log
CH 3COO  
CH 3COOH 
Typically a buffer is best when
it is within .5 units of its pKa
Blood, Lungs and extracellular
fluid is buffered by carbonate
Vigorous
Exercise
(lactic acid)
Typical
catabolism
raises pH
Blood,
extracellular Fluid
Vigorous
Exercise
Lungs, Air space
Typical
catabolism
raises pH
Enzymes have specific pH optimums due to
the combination of many functional groups