Chapter 1 9/4/2013 6:37:00 AM
Office hours: Monday, 3:00pm-4:00pm, 12 Waverly Place Room 306
The relationship between structure and function is crucial when
Each cell type is specialized to do a particular job.
Red blood cells don’t have a nucleus.
Microvilli have a particular function for nutrient uptake
All these different human cell types come from the coming together of two
different kind of cells (egg and sperm)
How do cells know where they are?
They listen to each other and their external environment (they send
and respond to signals)
All cells are aware of where they are in the body
There will be a protein that is responsible for receiving a
signal from the outside and sending it to the cell via other
This signaling process is very coordinated between several
proteins depending on the signal.
There are layers of complexity
This is called the signaling cascade (signaling transduction)
Prokaryotes and eukaryotes (prokaryotes consist of anything that are not
Organisms of our daily experience are only the surface of the
organisms that are in biology
o Enormous tree of life that has organisms we don’t even think
Consists of a nucleoid, inner membrane, outer membrane, and cell
o Nucleoid is the genetic material (DNA) that is loosely
organized in the middle of the cell
o Double membrane system
Consists of nucleus, golgi vesicles, lysosome, mitochondrion, and
o Cytoplasm is far more complicated o Nucleus has the genetic material that is organized in the cell
Not uniform – it has structure
Molecular and cell biology spans a huge size range
Nanometers to meters (10^-10 to 10^4)
A typical cell is around 10 microns
o Protein molecules are much smaller (around ten nanometers)
270 million proteins inside of every cell
All diseases can be linked to the change in one genome
for example sickle cell disease = base change in the
DNA a single change in an amino acid in a protein
different shape in a hemoglobin molecules a very
different shape in red blood cells sickle cell diseases
The number of copies of DNA per cell (in our bodies
that’s two. In some prokaryotes, that’s one) is a vast
range of molecule numbers as well
Each of our cells have 6 feet of DNA. Multiply that
by ten trillion cells.
Proteins are in extraordinarily high numbers two
Many copies of hemoglobin per red blood cell (we
are basically a hemoglobin factory)
We need exquisitely sensitive methods for
detecting particular proteins/molecules inside
We need something super specific
Biological molecules differ in size, shape, and function
The difference between a hemoglobin protein, insulin protein,
enzymes, etc. has to do with the structure of their cells
Model organisms – organisms that are used for experiments all over
o Biology has a certain kind of universality
o Mice, fruit flies, viruses
There are commonalities between species
Example: a gene in flies that has to do with eye
development (if you remove the gene, there is no
eye). Remove this gene in humans, and we get
amoridia (less of an eye in a human). Vast span of time – we’ve had a short flash of time compared to all the
diversity in Earth
The rise of non-model organisms
Now, people are directly studying organisms they are interested in
Increasing number of diverse species using sophisticated molecular-
genetic, cell-biological, and genetic material
Chapter 2 9/4/2013 6:37:00 AM
All activities in the cell happen simultaneously and must be coordinated.
Imagine that the cell is like a city.
Understand the government of the cell.
The job of the cell is basically done by proteins – they are made in the
cytoplasm (transportation issue)
Information is in the nucleus but the job is done by those made in
Central dogma here: DNA -> mRNA -> Protein
DNA makes messenger RNA, which makes Protein
o All of your cells have the exact same DNA.
Cells are not different because they have different DNA
– they are different in how they use the DNA they have.
Difference between Molecular Biology and Biochemistry: both care about the
chemistry of life. While biochemistry focuses on the reduction of science
(focused on actual activities of molecules based on chemical properties). In
MCB, we set this aside and focus on the information these molecules
contain. We emphasize information.
Proteins, nucleic acids, and polysaccharides – the most important
Phospholipids – make the outside of the cell
Phospholipids and monosaccharides are excluded from the central dogma
Chemical building blocks Think about DNA and small molecule subunits.
The macromolecules we care about (DNA, RNA, protein) are made of simple
building blocks put together in long strings. The small molecule subunits of
DNA are called nucleotides and the process of making DNA is the process of
assembling these nucleotides one after one.
DNA nucleotides – purine/pyramidine + five carbon sugar (deoxyribose) +
Deoxyribose has a Hydrogen in place of OH (ribose contains two
Adenine + Guanine + Thymine + Cytosine in DNA. In RNA it is the same
thing except you will have Uracil instead of Thymine.
Purines – adenine and guanine (two rings)
Pyramidines – Uracil, Thymine, Cytosine (one ring)
Pyramidines pair up with purines The way DNA/RNA is made into a long polymer is when the phosphate end
connects to the carbon of the previous phase (beginning the 5’ and 3’ ends)
Always add new bases to the 3’ end of the molecule. You must specify which
side the 5’ and 3’ end.
Chemical Bond Energy nucleotide triphosphates carry nuclear energy in
them so they have high energy bonds. When you break these bonds, you
get energy that powers polymerization of DNA/RNA in the cell. (ADP + Pi +
Adenosine Triphosphate is the most important energy currency in
the cell. ATP means energy.
o It is the energy currency but also the A that gets incorporated
Nucleic acid polymerization is powered by NTPs.
Read from 5’ 3’ when reading DNA
When you polymerize DNA from the template, directionality
C and G forms three hydrogen bonds; A and U forms two hydrogen
Pyrophosphatase converts two phosphate molecules linked together
The phase where you release pyrophosphate is energetically
Chemical equilibrium forward and reverse rates balance at equilibrium.
Many reactions do run in both directions, but their rates are
different. As products are formed, some of them will convert back
to reactants. There will be a point where the number of products
formed will equal the number of reactants that form from products.
At this point, the rates are equal.
o The reaction does not stop here. It keeps going, the rates are
o A rate constant is not the same as a reaction rate. A rate
constant describes the rate given the concentration of
reactant (represent the speed at which the reaction will
occur). The rate constant is high, the highest number of
reactants will convert to products.
Reaction rates change. But a rate constant does not. After the reactants are first mixed, the rate of the
reverse reaction slowly increases while the rate of the
forward reaction slowly decreases until chemical
equilibrium is reached and the two rates are equal.
o A useful way to summarize a reaction is through the
equilibrium constant (Keq).
K(eq) = Kf/Kr (the forward constant/reverse constant).
If Kf is three times larger than Kr then you will have
three times as much product than reactants in the
Cellular reactions are at a steady state, not equilibrium.
o Test tube equilibrium concentrations
o Intracellular steady-state concentrations.
o There is a system/network of reactions that is happening.
o Not every cell is in equilibrium – they could be at a steady
state where concentrations don’t change.
o Polymer + NTP > polymer + PPi 2Pi
This creates energy
By converting polymer + PPi into something else, you’re
siphoning away the products of Polymer + NTP. In this
case, the reverse reaction becomes much less likely.
This adds an extra layer of security. The reaction will
keep going forward instead of in reverse.
Molecular complementarity two different molecules fit together
Allows a complexity of function when you bring two or more things
together like this
What makes it so that two proteins have an affinity for each other?
o Shape – the shapes complement one another
o Weak interactions that draw them together as opposed to
Covalent bonds, interactions, etc.
Ionic bonds – electrons are being exchanged
In proteins a part of the molecule will have a
negative charge on it, and the other will have a positive charge. This causes them to be drawn
Hydrogen bond – weaker, longer than covalent bonds.
But if you add them up together, you get a relatively
Partial positive charge and partial negative charge
Hydrophobic effect – charged molecules dissolve easily in water.
This is because water is a dipole (It has a little excess of negative
and positive charge). In an aqueous environment, charge matters.
o Methyl groups have no charge and don’t interact well with
water so it separates from water
o Protein does not separate from water, which is good.
o Proteins form when hydrophobic residues go to the center of
the protein (by bonding together)
van der Waals interaction – when you put two atoms really close
together, the electrons start to perturb one another, which causes
transient dipoles. One will become positively charged, the other will
be negatively charged, and will eventually start to attract one
What happens if you have a mutation that changed the amino acid
sequence of a protein?
o The mutation can cause the stable complex to be less stable
Hydrogen bonds create the double helix
GC pairs form three hydrogen bonds, AT pairs form 2.
Therefore the more GC pairs you have, the stronger the DNA will be
(because there will be more triple bonds)
o If you put a strong strand of DNA pairs in an aqueous
solution, you would need a higher temperature to break these
o There are organisms that live in very hot environments (they
tend to have more GC base pairs).
In order to keep these base pairs, you need to have
more hydrogen bonds.
DNA strands are antiparallel
DNA is not evenly spaced – major groove and minor groove (the
spaces between each helix is different) o DNA spins about once every 1.2 bases Recitation 9/10/13 9/4/2013 6:37:00 AM
Study Question: The following sequence comprises one strand of a DNA
double helix. What is the sequence of it’s paired strand?
Answer: Read in 5’3’ direction. So it has to be the opposite way.
How many turns of the helix will this DNA turn?
Lecture prompt question
Nucleoside analogs serve what function in synthetic biology?
o What is a nucleoside?
o What is a nucleoside analog?
A nucleoside is a nucleotide without the phosphates (a
nucleoside is just the sugar and the base).
A nucleoside analog would be something that is similar
to the nucleoside but not exactly the same (a
nucleoside with a different base?)
Nucleic Acids & Origin of Life (based on reading)
What is life?
Being able to reproduce and having cells
How is a cell important to life? (Why is it the building block of life?)
A cell contains DNA and is the basic building block of life.
What is the paradox of cellular life?
o It takes proteins and DNA to make more proteins. This
paradox would disappear if molecules didn’t need proteins at
Earliest forms of life may have been able to get by
without proteins, using their DNA (or close relative
RNA) as catalysts to reproduce
How were the first organic molecules synthesized?
Stanley Miller in his 1953 experiment, a laboratory simulation
demonstrating that environmental conditions on the lifeless,
Spontaneous synthesis of some organic molecules with electrical
discharges (simulated lightning as reactions in a primitive
atmosphere of H2O, H2, NH3, and CH4 How did the first complex organic molecules form?
In a warm alkaline (basic) solution
Nucleobases can form spontaneously
Sugars are easy to assemble in those situations – the problem is
finding the right sugar (ribose for RNA and deoxyribose for DNA).
Ribose can form from two simple