Biochemistry Lecture 1

Chemistry inside the cell is carried out by

organic and inorganic molecules. One of the most
important molecules to support life is H2O

Organic molecules in the origin of life:

H2O, N2, CO2, CH4, NH3. Reactions among these
small molecules are initiated by UV (sun light) or
electricity (lighting in thunderstorm)

Reaction can also be underwater in the

hydrothermal vent (volcanic), which can have high
temperature and pressure

Reactions lead to the formation of simple

organic molecules, which can be further elaborated to
form complex biological molecules

Condensation: elimination of water (amide

bond formation, glycoside bond formation)

Hydrolysis is cleavage via water or lysis by

H2O
Organic Functional Groups

Amine, carboxylic acid, alcohol, thiol, ester, amide are important function in amino
acids and used in modulating protein functions.
o These functions groups can all be involved in many noncovalent interactions,
including H-bonding.
o In the biological world, noncovalent interactions play key roles in many
processes.
Thioester is a high energy molecule and are important in metabolism
Aldehydes and ketones are important for carbohydrates
Amide is the bond used to form the backbone of all proteins (peptide bond)
Imine is important for crosslinking proteins (eg. elastin in lung tissue and collagen gets
their elastic property from the imine group)
Disulfide bonds play an important role in stabilizing protein structures (eg. the disulfide
bonds in insulin hold it together) or as in electron transfer (redox chemistry)
Phosphate esters are used to form the backbone of DNA and RNA- can be used as
signals
Phosphoanhydride bonds are high in energy and used as energy carrier in biology
(ATP)

There are 4 major types of biological molecules, 3 of these are biopolymers

Biopolymers are linked by covalent bonds

o Note that lipids are NOT polymers since they are not held together by covalent
bonds
Polymers can fold up into three dimensional shapes or conformations which give them
their function
o Polymers allow complexity to arise from few building blocks
o Biopolymers are important because of their diversity

Problem: It is proposed that ancient organisms only had 8 amino acids. If so, how many
possible different proteins of 100 amino acids in length could exist?
o # of possible oligomers = (# monomers)length
o # of possible proteins = 8100 = 2 x 1090 proteins

One of the most important features of biological system is that it can replicate itself =
self-replication - parent leads to daughter cells
Template based synthesis is key for the precise replication of DNA, or for the
transmitting of information encoded in DNA to RNA or proteins
o For example, either DNA replication or RNA synthesis is mediated by replication
through Complementarity = allows transfer and correction of information.
o Complementarity gives you two things: (1) it allows things to come back together
and (2) brings things back together in different shapes (this allows for correction
in DNA)

One of the key features of living organism is that they separate their components from the
environments by cell membranes, which is called compartmentalization
(compartmentation)
Advantages of compartmentation: (1) Separate the cellular environment from the
outside (2) Enrich the molecules of interest, for example, nutrients (3) Get rid of toxic
molecules by efflux
Prokaryotic cells does not have internal compartments. However, the cytoplasm is
not homogenous. The cytoplasm is a very viscous environment so there can still be colocalization of macromolecules and small molecules.
o Prokaryotic cells are in general 1 10 m in size. (Human hair = 20-200 um)

Eukaryotic cells are 10X bigger, 10 100 m in size.

The key difference between prokaryotic and eukaryotic cells are that the eukaryotic
cells have defined nucleus (separated by nuclear membrane).
Besides the nucleus, eukaryotic cells can also have the following membrane-separated
compartments:
o Endoplasmic reticulum: site for the synthesis of many cellular components
o Golgi apparatus: protein modification and secretion
o Mitochondria: aerobic metabolism (the power plant in eukaryotic cells)
o Chloroplast: photosynthesis (plants)
o Lysosomes: digestion
o Vacuoles: used for storage (plants, some bacteria)
The compartments are very organized and are all bounded by lipids which are bounded
together by non-covalent bonds
The Cytoplasm is a thick solution that fills each cell and is enclosed by the cell
membrane. It is mainly composed of water, salts, and proteins. In eukaryotic cells, the
cytoplasm includes all of the material inside the cell and outside of the nucleus.
The Cytosol is the part of the cytoplasm that is not held by any of the organelles in the
cell
Cytoplasm = cytosol + membrane-bound oraganelles. Organized by cytoskeleton
Prokaryotic and eukaryotic cells evolve to suit their living environments.
o Prokaryotic cell grow fast and can tolerate significant environmental fluctuations
o Eukaryotic cells evolved to suit stable environments.

*Know basic sizes of cells & conversion of units (m - m)

The tree shape is made from ribosomal RNA and is called a phylogeny tree
o Shows we are more closely related to plants than bacteria
o Compare species by looking at shared polymeric molecules = DNA, RNA,
proteins phylogeny tree
The biological systems are roughly divided into three kingdoms:
o Eukaryotic system: animals, plants and fungal. They are only a very small
portion of the organisms on earth
o Arachaebacteria (archaea): are groups of bacteria that are distantly related to
other prokaryotes; often extremophiles meaning they live in unusual & extreme
environments
Halobacteria: live in high salt concentration
Methanogens: produce CH4
Thermophiles: live in hot springs
o Bacteria
Principles:
o Evolution is not directed toward a particular goal = random changes; those that
are non-destructive continue
o Evolution requires certain degree of flexibility (bio-diversity = less susceptible to
one fungal blight)
o Evolutionary is constrained by its past, which means that evolution is a gradual
process
o Evolution is ongoing.

Thermodynamics
Gibbs Free Energy G
Gibbs Free energy = energy available for work, made up of:
Enthalpy H
Entropy S
G = H - TS
G, H, and S can be expressed as a change () over the course of a reaction: A + B C
Gproducts Greactants = G
q = heat = random motion of molecules
H = q
Change in Enthalpy = change in internal heat of the system

1st Law of Thermodynamics: Energy is conserved (heat + work = total)

Biological systems exist under constant pressure, H = q (heat)
Changes in enthalpy H = q
Exothermic = release of heat
Endothermic = absorption of heat
How to determine direction of flow of heat? Spontaneity (does reaction move forward?)

Entropy (S) is disorder in a system; heating a system can also increase disorder

2nd Law of Thermodynamics: Entropy of the universe is increasing

Ssys + Ssurr = Suniverse > 0
Entropy change can be calculated from changes in heat/temperature: S > q/T;
But since H = q
S > H/T
This law defines criteria for spontaneity

If the entropy in a system decreases, entropy in surroundings must INCREASE to satisfy

2nd law
For a process to be spontaneous, entropy must increase.
Free Energy
S > H/T
TS > H
0 > H TS = G
Gibbs Free Energy determines spontaneity
G < 0 (negative) for spontaneous processes = Exergonic
G > 0 (positive) for non-spontaneous = Endergonic
G = 0 at equilibrium = when forward and reverse reactions are equally balanced

Spontaneity

H, S, and G are state functions.

Only need initial and final values to calculate
Pathway-independent
Free energy has two components: the enthalpy and entropy
Enthalpy change in biological system equals to the heat released or absorbed in the
reaction
Entropy change in any system equals to the degree of randomness changes. For
example, same amount of material in large volume will have more freedom and have
higher randomness
Entropy increases with volume; therefore depends on concentrations.
Free energy depends on concentration

Problem: For the reaction A B at

298K, the change in enthalpy is -7
kJ/mol and the change in entropy is
-25 J/mol. Is the reaction
spontaneous?
o H TS = G -7000
J/mol (298K)(-25 J/mol) =
+450 J/mol
o Non-spontaneous because
G > 0; decrease
temperature to make
spontaneous
One of the ways cells move along is by coupling reactions and making the overall reaction
spontaneous (eg. how glycolysis works)

The biological system is an open system. There is constant exchange of material and
energy between the biosystem and its environment.
Biological system take up nutrient, release waste, generate work and heat. It does not
reach equilibrium. Equilibrium = Death.
Since biological system maintain high order inside the organism (S < 0), thus, S > 0
for the environment. Must compensate by making the environment more disordered.
Food = high enthalpy, low entropy Waste = low enthalpy, high entropy (CO2, H2O)

Energy input needed to maintain direction of G (with +S at constant T). To have

spontaneous process, enough H.
Couple energy releasing process to one that require energy input.
Steady state Flux in = flux out. No overall net change with time. Small perturbations
in molecules restore back to steady state.
Energy flow is downhill (G < 0), and not completely efficient, so some energy is lost
to surroundings (Suniverse > 0) and increases the overall entropy of the system. (ex: low
entropy inside our bodies to high entropy outside)
C6H12O6 + O2 6 CO2 + 6 H2O; G = -2870 kJ/mol only 1/3 of this energy is
converted into biochemical energy (ATP)

Photosynthesis couples favorable redox reactions to unfavorable reduction of CO2

o Photosynthesis is coupling the unfavorable reduction (adding hydrogens)
with favorable oxidation (adding oxygen)
Catabolism couples favorable redox reactions to unfavorable oxidation to CO2
Scale: formaldehyde is more reduced than carbon dioxide, etc.

Rate of biological process

Thermodynamic control = is a reaction spontaneous (possible)?

Kinetic control = how fast will a reaction occur?
o Its possible for a reaction to be very spontaneous but very, very slow. It depends
on the kinetics of the reaction
Biological catalyst = enzyme, helps the reaction get over the kinetic barrier
o Provide a more favorable pathway from reactants to products
o Enzymes provide kinetic control but NOT thermodynamic control
Thermodynamics is pathway independent. Kinetics is not.
Reaction coordinate to compare change in G vs pathway

Problem: True or False

o A reaction is said to be spontaneous when it can proceed in either the forward or
reverse direction.
False spontaneous only in 1 direction
o A spontaneous process always happens very quickly.
False kinetics not thermodynamics tells you the rate
o A non-spontaneous reaction will proceed spontaneously in the reverse direction.
True
o A spontaneous process can occur with a large decrease in entropy.

True, as long as S > H/T so G is negative.

Summary of Chapter 1

Polymeric structure of key biomolecules

Complementarity is important for self-replication
Thermodynamic control determines spontaneity (-G), can be adjusted by coupling
reactions
Biological systems are open and at steady state, NOT at equilibrium
Kinetic control determines rate
Suggested Book Problems: Ch 1: 1, 17, 23, 25, 29, 31, 33, 37, 39, 41