DAT Bootcamp Bio Academy

Chapter 1: Fundamentals of Biology

Table of Contents:
Biological Chemistry
Carbohydrates
Proteins
Lipids
Nucleic Acids
Biological Hypothesis and Theories
Preview
Biology is a broad topic with many details. However, we need to have an
appreciation for the big picture of biology before we can dive into those details.
Specifically, we need to gain an understanding of the chemical properties that
govern biology. These chemical properties give biological systems their
characteristic features, and they are also responsible for creating the various
macromolecules that are essential to life.
In this introductory chapter, we will emphasize fundamental concepts that we
will need to keep in mind for the duration of our biology journey. First, we will
discuss biological chemistry and critical macromolecules, which are responsible
for life as we know it - these include carbohydrates, proteins, lipids, and nucleic
acids. Finally, we will look at biology in a more thought-provoking manner as we
discuss central hypothesis and theories.

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 Biological Chemistry
All of the stuff around us is called matter, which refers to any substance that
takes up space and has mass. Matter is composed of elements, which we all
know from the periodic table of elements. However, just what is an element? An
element is a substance that has specific chemical and physical properties.
Note: we have access to a periodic table during the Survey of Natural
Sciences section of the DAT - so do not worry about memorizing the periodic
table!

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 Adapted from: https://commons.wikimedia.org/w/index.php?curid=62296883
An atom is the smallest unit of matter that still retains all the chemical properties
of an element.
Molecules result whenever two or more atoms join together. An example of a
molecule is oxygen gas O₂), which we breathe in every day. Organic molecules
contain carbon atoms arranged as long chains or rings, and these carbon atoms
tend to bond with hydrogen H , oxygen O , or nitrogen N atoms.

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 Adapted from: https://commons.wikimedia.org/w/index.php?curid=47225413 and
https://commons.wikimedia.org/w/index.php?curid=7536683

Intramolecular forces are strong attractive forces that hold atoms within a
molecule.
Intermolecular forces exist between molecules, and they are far weaker than
intramolecular forces. However, intermolecular forces are significant because
they determine physical properties (boiling point, melting point, density, and so
on).

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 https://commons.wikimedia.org/w/index.php?curid=1515822
In this image, intramolecular forces exist between H and O in a single molecule,
while intermolecular forces exist between O and H in different water molecules
Monomers are molecules that have the potential of bonding to other identical
molecules through chemical reactions. Bonding in this way is known as
polymerization, and it forms polymers. Polymers are substances that have a
large number of units (monomers) bonded together. Polymerization is an essential
concept for our later discussion of carbohydrates, proteins, and nucleic acids.
Critical Review of Biological Chemistry:
Atoms are the smallest unit of matter that retains the properties of an
element
Intramolecular = within a molecule; intermolecular = between molecules
Carbohydrates
Carbohydrates are macromolecules that contain carbon, hydrogen, and oxygen
atoms. Carbo- means carbon and -hydrate means water. Carbohydrates contain
roughly one carbon atom per water molecule. Carbohydrates come in varieties
including monosaccharides, disaccharides, and polysaccharides.

https://www.youtube.com/embed/LeOUIXbFyqk

Monosaccharides mean “one sugar” because mono- means one and -sacchar
means sugar. Monosaccharides have a ratio of precisely one carbon to a water
molecule, and they have the empirical formula CH₂O)n - where n is equal to the
number of carbons.
Monosaccharides will usually have anywhere from three to seven carbon atoms.
Five carbon sugars are called pentoses, and six carbon sugars are called
hexoses.

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 Whenever a linear pentose or hexose sugar converts to a ring structure, it forms a
hydroxyl OH functional group. The positioning of that hydroxyl will determine
the classification of the monosaccharide.
If the hydroxyl group points down the sugar is an alpha (α) sugar. Conversely, if
the hydroxyl points up the sugar is known as a beta (β) sugar.
Some monosaccharides to be familiar with for the DAT include ribose, fructose,
and glucose.
Don’t worry about being able to draw their structure. The main things to know
are that ribose is a five carbon sugar, and that glucose and fructose are six
carbon sugars.
Additionally, it’s helpful to know that fructose and glucose are isomers of each
other, meaning they have the same atoms just arranged differently.
Disaccharides are “two sugars”, as di- means two and -sacchar means sugar.
These form when two monosaccharide monomers join together via dehydration
reactions (also known as condensation reactions).
In dehydration reactions, the hydroxyl group of one molecule will combine with
hydrogen on another molecule. In this way, the two molecules form a covalent
bond with the release of water. Hydrolysis reactions are the exact opposite of a
dehydration reaction. Here, water ads to a covalent bond and splits monomers
apart.
Whenever a carbohydrate attaches to another molecule, the bond is called a
glycosidic bond

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 Adapted from: https://commons.wikimedia.org/w/index.php?curid=49922737
Don’t worry about the structures, this is just an example of a glycosidic bond
forming.
Some disaccharides to be familiar with for the DAT are sucrose, lactose, and
maltose.
Again, don’t worry about needing to be able to draw out their structure.
Sucrose contains one glucose and one fructose.
Lactose contains one galactose bound to one glucose.
Maltose contains two glucose monosaccharides linked together.
Polysaccharides are long polymers of monosaccharides, where each
polysaccharide contains many (poly-) monomers. Polysaccharides may or may
not have branching, and the role of a polysaccharide depends on the
physiological system and monosaccharides it contains. Some polysaccharides are
for storage, and others are for structure.

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 Starch is a crucial storage polysaccharide in plants, containing many glucose
monomers in linear forms as well as branched forms.
Linear plant starch is called amylose, and it contains α-1,4 glycosidic bonds.
Amylopectin is the branched form of plant starch, and it contains both α-1,4
glycosidic bonds and α-1,6 glycosidic bonds.
Glycogen is a critical storage polysaccharide found in humans, and it contains
many glucose monomers with more branching than amylopectin.
Glycogen contains α-1,4 glycosidic bonds and a lot of α-1,6 glycosidic bonds.
Glycogen is primarily in liver and muscle cells, and it is broken down to release
glucose monosaccharides to cells that need energy.

Don’t worry about recognizing α-1,4 vs α-1,6 bonds - this is just to illustrate that
both types exist
Cellulose is a structural polysaccharide in plant cell walls, wood, and paper.
Cellulose is a glucose polymer (like the polysaccharides discussed above);
however, it contains β-1,4 glycosidic bonds. In this way, the cellulose forms
linear strands that pack together in parallel, where adjacent strands are held
together by hydrogen bonds. In all, cellulose has a high rigidity due to its
structure.

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 Pro-Tip: humans cannot digest cellulose; instead, it passes through our digestive
tract as fiber.
Chitin is another structural polysaccharide that we should be familiar with for the
DAT. Chitin is virtually identical to cellulose, and it is found in the cell walls of
fungi (which are not animals or plants), and in the robust external skeleton
(exoskeleton) of insects.
Chitin has β-1,4 glycosidic bonds that allow the polysaccharide strands to
arrange in parallel. However, one of the hydroxyl groups in each glucose molecule
gets replaced by a functional group containing nitrogen N ; therefore, chitin is a
polymer of N-acetylglucosamine.
Critical Review of Carbohydrates:
Carbohydrates can be mono-, di-, or polysaccharides
Monosaccharides have a general form of CH₂O)n
Dehydration synthesis/condensation brings monosaccharides together
Hydrolysis reactions break carbohydrate polymers apart
Glycosidic linkages occur when a carbohydrate binds to something else
Know sucrose, lactose, and maltose disaccharides
Starch and glycogen are storage polysaccharides
Cellulose and chitin are structural polysaccharides
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 Proteins
Proteins are some of the most abundant macromolecules in biology, and they
come in a variety of shapes, sizes, and functions. Here, we will examine the
structure of proteins, as well as the function of some important classes of
proteins.
All proteins contain polymers called polypeptides. Each polypeptide contains
monomeric subunits called amino acids, which share a standard structure.
All amino acids have an alpha (α) carbon in the center, which is attached to an
amino group NH₂), hydrogen atom H , and carboxyl group COOH .
Note: at physiological pH (the pH in the human body), the amino group tends
to be protonated NH₃⁺), and the carboxyl group tends to be deprotonated
COO⁻).

Notice that amino acids also contain a variable group, known as an “R group.”
Because of the variability of these groups, twenty different amino acids show a
range of properties, such as acidity, basicity, polarity, and nonpolarity. We do not
need to memorize the amino acids for the DAT.

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 Remember, polypeptides are polymers of amino acids. Each amino acid monomer
is attached to its neighbor via a special covalent bond called a peptide bond.
Just like we saw during our discussion of carbohydrates, amino acids form
peptide bonds with each other via dehydration/condensation reactions.
Similarly, hydrolysis reactions will separate them. A peptide bond is what we call
an amide bond when it involves amino acids, and an amide bond is an amine
NH₂) bonding to a carboxylic acid COOH .

Unique enzymes (we will discuss enzymes in a little bit) called peptidyl
transferases help peptide bond formation. Peptidyl transferases belong to a
broader class of enzymes, known as aminoacyl transferases. Aminoacyl tRNA
synthetase is another type of aminoacyl transferase we will discuss in Chapter 6
Molecular Genetics.
Due to the structure of amino acids, polypeptides have specific ends. For
example, if we consider the dipeptide (a peptide containing two amino acids) in
the picture above, we will see that the left has an amino group NH₂) and the
right has a carboxyl group COOH . For this reason, polypeptides are said to have
an amino and carboxyl terminus. We may also refer to these as the N-terminus
(for amino) and C-terminus (for carboxyl).

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 Now that we understand polypeptides, we can start to look at the bigger picture
of protein structure and function. To do that, we need to discuss the four levels
of protein structure - primary, secondary, tertiary, and quaternary.
1. The primary structure is the specific order (or sequence) of a peptide, which is
determined by DNA genes. The primary structure is basically what we just learned
about in our discussion of polypeptides and peptide bond formation. All proteins
have primary structure.
2. Secondary structures are folds that occur in a polypeptide chain, due to
intermolecular interactions between atoms of the polypeptide backbone. A
polypeptide backbone is just the amino acid structural features other than the R
group. In other words, the secondary structure does not involve R-group atoms.
The most common type of intermolecular forces that leads to secondary protein
structure is hydrogen bonding. Hydrogen bonds can only occur between
hydrogen H and fluorine F , oxygen O , or nitrogen N . Therefore, hydrogen
bonds occur between carboxyl COOH and amino NH₂) groups. Two of the
most common secondary protein structures are β-pleated sheets and α-helices.
DAT Pro-Tip: most (but not all) proteins have at least secondary structure.

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 3. Tertiary structure is the three-dimensional structure of larger polypeptide
chains, which occurs at the result of interactions between R-groups of the various
amino acids. R-group interactions can include ionic bonding, hydrogen bonding,
dipole-dipole interactions, and London dispersion (van der Waal) forces.
Hydrophobic interactions are another critical R-group interaction that can cause
tertiary structure. Here, amino acids that have hydrophobic (water-
hating/nonpolar) R-groups will cluster together to avoid coming in contact with
water molecules. In this way, amino acids that have hydrophilic (water-
loving/polar) R-groups will come in contact with the aqueous environment.
While you don’t need to bother memorizing the twenty amino acids, it is good to
know that that amino acid cysteine contains sulfur S in its R-group. Cysteines
can create disulfide bonds with each other. Disulfide bonds are incredibly strong
bonds that act to hold the three-dimensional structure of the polypeptide in
place.
Note: tertiary structure interactions are usually not covalent; however,
disulfide bonds are the exception.

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 4. Quaternary structure refers to large proteins that have multiple subunits (i.e.,
they contain multiple polypeptide chains), which come together by the same
general interactions seen for tertiary structure. It is important to note that while
there are multiple polypeptide chains in a quaternary structure, we consider the
entire structure as being one protein.
Structural and compositional components are fundamental to a protein because
they relate to the function of that protein. For example, hemoglobin is a common
tetramer protein (it has four subunits) with primary, secondary, tertiary, and
quaternary structure. Hemoglobin's shape is crucial to ensuring that hemoglobin

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 can carry out its role of transporting gases through the blood. The table below
shows some protein classifications to give us a better understanding of proteins.
Protein denaturation occurs whenever a functional protein loses its higher order
structures. In other words, denaturation causes proteins to lose their secondary,
tertiary, and quaternary structures (if they have them). Note that denatured
proteins retain their primary structure; however, the loss of shape leads to a loss
of protein function.

Protein denaturation can occur by excess temperature, chemicals, pH changes,

and radiation to name a few. Some denatured proteins can fold back into their
functional shapes, which tells us that all of the information necessary for the
folding of those proteins is contained directly within the amino acid sequence.
However, other proteins cannot fold back into their regular shape. For example,
consider what happens when cooking an egg. The egg white contains a protein
called ovalbumin, which goes from appearing clear and runny when raw, to white

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 and stable when cooked. No matter what we do, the ovalbumin is denatured, and
we cannot get it back to its raw state.
Now that we know how critical shape is to a protein’s function, we can begin to
think about some of the specific functions proteins play in biological systems.
The table below will offer a brief survey, and keep in mind that we will describe
each of these categories (and their examples) in depth in later sections of this
book.

Catalysts are molecules that increase reaction rates. Despite speeding up

reactions, catalysts do not affect the spontaneity of a reaction. In other words,
they do not change the likelihood that a reaction will take place. An important
point to note is that catalysts are not used up by the reactions they manipulate,
meaning the reaction does not change them in any way.
Catalysts lower activation energies to speed reactions. Activation energy is the
amount of energy a chemical reaction requires to progress. Imagine trying to kick
a ball over a hill. It is much easier to kick a ball over a small hill than a large one.

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 Catalysts function to make the “hill” smaller by reducing the energy of the
transition state (unstable intermediate) between reactants and products - this
reduces the activation energy.
Even though catalysts reduce the energy of the transition state, they do not
change the net amount of energy a reaction might absorb or release. In other
words, catalysts do not change energy absorbing reactions to energy releasing
ones, or vice versa.
For example, consider that we are kicking a ball from an original elevation of
fifty-feet above sea level, and we are trying to kick the ball over a hill to get it to
our friend who is standing below our original elevation, at sea-level. The size of
the hill affects how fast we can get the ball to our friend; this is the activation
energy, and the precise height of the hill represents the energy of the transition
state.
However, reducing the height of the hill (lowering the activation energy) does not
change the fact that the ball is experiencing a net loss in elevation of fifty feet -
in other words, the ball is still ending up at the same place. This example shows
that catalysts do not affect the energy of reactants or products.

Enzymes are biological, globular (usually) protein catalysts that speed up

specific forward and reverse reactions by lowering their activation energies.
Because enzymes are catalysts, they do not affect the spontaneity of reactions,

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 and they are not used up by the reactions they affect. Moreover, enzymes only
change the energy of the transition state, not of the reactants or products.
Enzymes catalyze reactions by binding to reactant molecules, which are called
substrates. Some reactions convert one substrate into smaller products, and
others conglomerate smaller substrates into fewer large products. An enzyme's
active site is where substrates bind.
Because most enzymes are proteins, amino acids give the active site unique
properties and substrate specificity. The degree of active site specificity varies
from enzyme to enzyme; however, most are specific for a narrow range of
substrates. An enzyme's specificity constant measures how efficient an enzyme
is in converting substrate to product. When the specificity constant is high, the
enzyme’s active site will have a high substrate affinity, and the enzyme is highly
efficient.
Scientists used to believe that substrates fit into active sites the same way a key
fits in a lock. However, we now know that the “lock and key” model is not
accurate. In actuality, enzyme active sites change their shape ever so slightly
when substrate binding occurs. The change in shape allows for a better, tighter fit
of the substrate in the active site. We know this as the induced fit theory.

Most enzymes are proteins; however, other types exist as well. One such example
of a non-protein enzyme is a ribozyme. A ribozyme is a ribonucleic acid RNA
molecule that is capable of acting as an enzyme by changing the speed of
reactions as they progress from reactants to products. We will discuss more
regarding RNA and ribozymes in future sections.
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 Cofactors are non-protein molecules that assist enzymes in the reactions they
manipulate. Usually, cofactors assist by donating or accepting some component
of the reaction, such as electrons. Coenzymes are organic cofactors, and these
usually include things like vitamins. Inorganic cofactors tend to be metal ions,
such as iron Fe²⁺) or magnesium Mg²⁺).
Holoenzymes refer to enzymes that are bound to their cofactor, whereas an
apoenzyme is an enzyme that is lacking (not bound to) its cofactor. Cofactors
that tightly/covalently bind to their enzyme in a holoenzyme are known as
prosthetic groups.
Protein enzymes have optimal temperature and pH ranges in which they have
the highest enzymatic activity. Temperature and pH can denature protein
enzymes if they are too far out of the normal physiological range, resulting in a
loss of functionality.
DAT Pro-Tip: temperature ranges at the upper end of a normal physiological
range generally increase enzyme function, allowing reactions to proceed
faster.

https://www.youtube.com/embed/qgVFkRn8f10

Competitive inhibition is a form of enzyme regulation, where inhibitors compete

with substrates for active sites. As we increase the amount of substrate, there is a
higher chance that the substrate can bind to the active site - this is why we can
outcompete a competitive inhibitor by adding more substrate.

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 Adding more substrate will only increase the speed of catalysis until all active
sites are occupied (enzyme saturation). As saturation begins to occur, adding
more substrate will have diminishing returns in increasing the speed – this is when
plateau starts to occur.

Noncompetitive inhibition is when an inhibitor binds to the allosteric site of an

enzyme – a different location that is not the active site of enzyme catalysis. An
inhibitor binding to the allosteric site modifies the active site so that the substrate
has reduced binding or cannot bind.
It does not matter how much substrate we add. If the active site cannot bind to
the substrate when the allosteric inhibitor is present, increasing the substrate
concentration will not increase catalysis. We cannot outcompete allosteric
inhibitors by adding more substrate, which is why they are known as
noncompetitive inhibitors. The rate of enzyme catalysis is unaffected by
increasing the substrate concentration.
Now let’s consider an enzyme kinetics plot to understand how inhibitors regulate
enzymes. First, there are a few definitions to get down. The velocity V of a
reaction is merely the rate at which a reaction is occurring, and Vmax is the

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 maximum reaction velocity. In enzyme kinetics, we are also interested in the
substrate concentration X .
Increasing the substrate concentration X tends to increase the rate of a reaction
until enzymes become saturated with substrate, at which point increases in
reaction rate start to level off. The Michaelis Constant KM is the substrate
concentration X at which the velocity V is 50% of the maximum reaction
velocity Vmax).
A small KM implies that we only need a little bit of substrate because enzyme
ability/function is high. On the other hand, a large KM implies that we need many
substrates for reaction progression because enzyme availability/function is low.

The above plot represents a standard enzyme kinetics graph. The Vmax is the
maximum velocity. Notice the velocity plateaus as we move to the right of the
graph (i.e., as we increase the substrate concentration). Eventually, increasing the
substrate concentration will not lead to an increase in velocity, as enzyme active
sites are saturated.
An analogy would be increasing the number of car parts in a car factory, but not
increasing the number of workers. The car parts are the substrate, and the
workers are the enzymes. Eventually, as all the workers are working at their

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 maximum capacity, adding more available car parts will not increase the
production of cars because the workers are all fully occupied.
How would this plot change if we add a competitive vs. a noncompetitive
inhibitor? Well, if we add a competitive inhibitor, KM increases, while Vmax stays
the same. Conversely, if we add a noncompetitive inhibitor, KM stays the same,
while Vmax decreases. Let’s take a look at why these changes occur.
A competitive inhibitor competes for the active site of the enzyme, and as we
add more and more substrate, the probability that a substrate will occupy the
active site over a competitive inhibitor increases. Therefore, the substrate
concentration X required to reach 50% of Vmax increases, meaning KM
increases; however, the Vmax is unaffected.

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 A noncompetitive inhibitor binds at the allosteric site of enzymes, and
increasing the substrate concentration X will only increase the velocity V a
certain amount because we cannot outcompete allosteric inhibitors. Therefore,

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 KM remains the same in noncompetitive inhibition because the Vmax decreases,
which proportionally decreases the substrate concentration X required to reach
50% of the new Vmax.

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 https://www.youtube.com/embed/4KvTLZL9aHc

Critical Review of Proteins:

Polypeptides are polymers of amino acids
All proteins have primary structures, most have secondary structure, some
have tertiary structure, and select large proteins have quaternary structure
Protein shape is critical to protein function, so denaturation leads to
nonfunctional proteins
There are many categories of proteins, including enzymes which act as
biological catalysts

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 Enzyme regulation can occur through competitive or non-competitive
inhibition
Increased KM = worse substrate binding by the active sites of enzymes
Decreased KM = better substrate binding by the active sites of enzymes
Lipids
Lipids are hydrophobic, non-polar molecules, meaning they do not mix well in
water. Most lipids have long hydrocarbon (hydrogen bound to carbon) chains;
however, there are a few exceptions. The different varieties of lipids have diverse
roles in biological systems. Lipids store energy, provide insulation, contribute to
cell membranes, and lead to the synthesis of critical hormones.
A typical lipid molecule many of us are already familiar with is known as fat,
which might also go by the name triacylglycerol or triglyceride. Triglycerides are
in cells called adipocytes. Fats have two unique parts - a glycerol backbone and
three fatty acids.
Glycerol is a small, organic alcohol molecule that has three carbons and three
hydroxyl groups. A fatty acid is a long hydrocarbon tail attached to a carboxylic
acid. Most triglycerides contain fatty acids that have twelve to eighteen carbons.
However, there are undoubtedly exceptions to that generality.
Fats are produced by dehydration/condensation reactions, just like we saw for
carbohydrates and then proteins. Here, the hydroxyl groups of the glycerol
molecule react with the carboxylic acids of fatty acids to produce an ester
linkage (you’ll learn about esters in organic chemistry), accompanied by the loss
of water. In the same regard, the addition of water to a fat’s ester bonds will
break the fatty acids off the glycerol backbone by a hydrolysis reaction.

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 It is important to note that fats can contain fatty acids that are all the same
length; however, many fats contain fatty acids that are of different lengths and
degrees of unsaturation.
If a fatty acid tail has no double bonds, it is saturated. All carbons in a saturated
fatty acid are bound to as many hydrogens as possible. As a result, saturated
fatty acids are straight and can pack tightly. At room temperature, saturated fats
are solid (think of butter).
Unsaturated fatty acids can possess one or more double bonds because they do
not have full hydrogen saturation. Monounsaturated fatty acids have one double
bond. On the other hand, polyunsaturated fatty acids have two or more double
bonds.
Cis-unsaturated fatty acids create kinks in the fatty acid chain because the
hydrogens associated with the double bond remain on the same side. The kinks
caused by cis-unsaturation make it difficult for fatty acids to pack together
tightly. As a result, cis-unsaturated fats tend to be liquid at room temperature
(think about olive oil).
Trans-unsaturated fatty acids have hydrogens that go to opposite sides of the
double bond, which makes them pack together tightly. In nature, trans-
unsaturated fats are rare. However, trans-fats are common in the industrial
hydrogenation of cis-unsaturated fats. Industrial hydrogenation is performed to
give cheaper oils (like canola oil) the desirable room-stable properties of more
expensive products, like butter.

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 Phospholipids are a unique type of lipid (fat) in cell membranes. Each
phospholipid has a three-carbon glycerol backbone, attached to one phosphate
group and two fatty acid tails. Phospholipids are a classic example of an
amphipathic molecule because their phosphate group is polar and hydrophilic,
while the fatty acids are nonpolar and hydrophobic. Amphipathic molecules
contain hydrophobic and hydrophilic parts.
DAT Pro-Tip: another type of lipid molecule (called a glycolipid) looks
virtually the same as a phospholipid; however, these contain a carbohydrate
molecule in place of the phosphate group.
Because phospholipids are amphipathic, they spontaneously self-assemble into
a bilayer when in an aqueous environment. Both the extracellular (outside a cell)
and intracellular (inside a cell) environments are aqueous; therefore, cell
membranes form through self-assembly of phospholipids.

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 Cholesterol is another class of lipid that makes up around 30 50% of a
eukaryotic cell membrane. Cholesterol contains four hydrocarbon rings and is
also amphipathic, which allows it to interact with various regions of the
phospholipid bilayer.

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 The ability of cholesterol to interact with the cell membrane is beneficial to the
overall fluidity of the membrane. Several factors influence the fluidity of a
membrane; they are temperature, cholesterol, and the degree of unsaturation in
the phospholipid fatty acid tails.

https://www.youtube.com/embed/BWQCAsM CF4

This video is licensed by Khan Academy under CC BY NC SA 3.0 US at

https://creativecommons.org/licenses/by-nc-sa/3.0/us/. The original version can
be found at https://www.youtube.com/watch?v=BWQCAsM CF4.
When it is cold, phospholipids pack together tightly. Conversely, when it is hotter,
the phospholipids of the cell membrane they are found further apart. Cholesterol
maintains some distance between the phospholipids when it is cold, but it also
holds the phospholipids together when it starts to get hot.

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 Without cholesterol, cell membranes would become overly rigid in the cold. This
reduced flexibility could result in the cell membrane “shattering” altogether. On
the other hand, cell membranes (without cholesterol) would become too flexible
in hot environments. Increased flexibility would result in gaps opening up between
the phospholipids, causing the membrane to be “leaky.”
Another thing to keep in mind is that cells will increase or decrease the degree of
unsaturation in the phospholipid fatty acid tails based on the temperature. For
example, when it is cold, cells increase fatty acid unsaturation in their
membranes to decrease rigidity and maintain fluidity. Conversely, when it is hot,
cells decrease fatty acid unsaturation in their membranes to increase rigidity and
maintain fluidity.
The liver makes cholesterol, and we can also get it from the diet. Cholesterol is
an essential molecule because of the roles it plays in membranes (which we just
saw), it is a starting material for vitamin D, and it is a precursor to bile acids that
aid in fat absorption (bile is discussed in more detail in the digestion chapter).
Cholesterol is also the most common steroid precursor (meaning it makes
steroids). Steroids are fused structures composed of three six-membered rings
(cyclohexanes) and a five-membered ring (cyclopentane). Examples of steroids
include cholesterol and the sex hormones (including testosterone and estrogen).

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 Adapted from: https://commons.wikimedia.org/w/index.php?curid=61794217

Recall that lipids are nonpolar, hydrophobic molecules. As a result, they travel
through blood in structures called lipoproteins. Lipoproteins contain a coat of
phospholipids, cholesterol, and proteins. Lipoproteins also have a lipid core that
contains more cholesterol and triglycerides. In this way, the hydrophobic lipids
can travel through aqueous environments (like blood) by traveling in lipoproteins.

Low-density lipoproteins LDLs) have a low density of proteins. They are

generally considered to be unhealthy because they deliver cholesterol to

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 peripheral tissues via the bloodstream. In this way, they can deposit cholesterol in
the heart and major blood vessels, leading to atherosclerotic blockages and heart
disease. LDLs are the “bad” cholesterol.
High-density lipoproteins HDLs) have a high density of proteins. They are
generally considered to be healthy because they take cholesterol away from
peripheral tissues and deliver it to the liver. Once at the liver, the cholesterol can
be used to make bile acids, which aid in fat absorption as was mentioned above.
HDLs are the “good” cholesterol.
Some other lipid derivatives to remember for the DAT include waxes and
carotenoids.
1. Waxes contain long fatty acids that are connected to monohydroxy alcohols
by ester linkages. Monohydroxy alcohols are molecules that contain just one
hydroxyl group. Waxes are often a hydrophobic protective coating; for
example, many leaves are coated with wax so that water beads off of them.
Animals with wool and feathers also secrete wax to ensure they are not
weighed down by water absorption.
2. Carotenoids are long fatty acid carbon chains that have conjugated double
bonds (shown in red in the picture below) and six-membered rings at each
end. Carotenoids function as pigments that provide color to plants and
animals. Some examples include carotenes and xanthophylls, which we will
discuss in greater detail in Chapter 4 Photosynthesis.

Adapted from: https://commons.wikimedia.org/w/index.php?curid=1828495 and

https://commons.wikimedia.org/w/index.php?curid=4052606

Critical Review of Lipids:

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 Lipids are a diverse class of essential, nonpolar, hydrophobic macromolecules
Fats have glycerol, three fatty acids, and they store energy in adipocytes
Phospholipids are amphipathic lipids that contribute to cell membranes
Degrees of unsaturation in phospholipid tails affect membrane fluidity
Temperature and cholesterol affect membrane fluidity
Cholesterol is an amphipathic steroid precursor with four rings
Steroids, waxes, and carotenoids are lipids
Lipoproteins transport lipids through physiological aqueous environments
(blood)
Nucleic Acids
https://www.youtube.com/embed/MA-ouz1LtpM

Nucleic acids are essential macromolecules in living biological systems.

Deoxyribonucleic acid DNA is a type of nucleic acid found in living organisms
as small as bacteria and as large as elephants. DNA passes from parents to their
offspring, and it contains genetic information (or “blueprints”) that cells use to
make products, like proteins.
Ribonucleic acid RNA is another type of nucleic acid. Some viruses use RNA as
their genetic information; however, we also find RNA in the same living organisms
that contain DNA. For cells to make proteins from their DNA blueprint, they must
convert the section of the DNA that has the instructions for that protein into an
RNA molecule. Therefore, DNA makes RNA, which makes proteins.
DAT Pro-Tip: not all DNA is destined to give rise to a protein; sometimes,
converting the DNA into RNA is the goal because specific RNA can act as
ribozymes.

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 Nucleosides have a pentose (five-carbon) sugar attached to a nitrogenous base.
A nucleotide is a pentose sugar attached to a nitrogenous base and a single
phosphate group. Nucleic acids are polymers made of nucleotides. When we have
more than one phosphate group, we call the molecule a nucleoside di- or
triphosphate.

All DNA and RNA are nucleotide polymers; however, DNA and RNA differ a bit in
their structure. First, we will discuss how DNA and RNA nucleotides are different
in their bases and sugars, and then we will see how the overall polymer structure
differs.
Each nucleotide in DNA can contain one of the following four nitrogenous bases -
adenine A , thymine T , cytosine C , or guanine G . RNA nucleotides can
contain one of the following four bases  A, C, or G; however, uracil U replaces
T in RNA.
A and G nitrogenous bases are known as purines, while C, U, and T are known as
pyrimidines. We can use the following two mnemonics to remember precisely
which bases are purines and which bases are pyrimidines:
PUR As Gold = PURines are Adenine and Guanine
CUT the PY = Cytosine, Uracil, and Thymine are PYrimidines.
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 Purine molecules have two rings, while pyrimidines have just one ring. Remember
that purines (the shorter name) are large molecules, while pyrimidines (the longer
name) are small molecules.
Note: do not worry about memorizing these structures - this is to illustrate
purines vs. pyrimidines.

Now that we have seen how the bases can differ between DNA and RNA let’s
examine the pentose sugars. RNA nucleotides have ribose sugars with a hydroxyl
group on the 2’ (“two prime”) carbon. DNA nucleotides are slightly different
because they have deoxyribose sugars, meaning the 2’ carbon does not contain
oxygen. RNA is more reactive (less stable) than DNA because of its 2’ hydroxyl.

At this point, we should discuss how phosphate groups of a DNA/RNA nucleotide

come into the equation. Phosphate groups attach to the nucleotide sugar at the

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 5’ carbon. The 5’ phosphates of one nucleotide connect to the 3’ hydroxyl of
another nucleotide in nucleic acid polymers. Bonding in this way is known as a
phosphodiester bond. Phosphodiester bonds create the sugar-phosphate
backbone of nucleic acid polymers.

Notice that nucleic acid strands have directionality due to the structure of their
nucleotides. In other words, the picture above shows us that the 5’ end has a free
phosphate, while the 3’ end has a free hydroxyl.
Nucleoside triphosphates add to growing nucleic acid polymers by losing two
phosphates (as pyrophosphate) to form a phosphodiester bond with the free
hydroxyl at the 3’ end of the polymer - this is how nucleic acid polymerization
occurs.

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 DNA manifests as a double-stranded helix, where two complementary strands
twist around each other. The sugars and phosphates lie on the outside of the
helix, forming a sugar-phosphate backbone. Conversely, the nitrogenous bases of
each nucleotide face the interior of the helix and hydrogen bond H-bond) with
their complementary base.
Just what is a compliment base, and how does it make two strands
complementary? Well, we need to consider that only specific bases can H-bond
with each other - purines can only H-bond to pyrimidines (and vice versa). In
other words, adenine can only H-bond to thymine and cytosine can only H-bond
to guanines in DNA.

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 Recall that we said nucleic acid polymers have directionality, with a 5’ end and a
3’ end. In a DNA double helix, the strands are antiparallel. In other words, the
base attached to the nucleotide at the 5’ end is complementary to the base
attached to the 3’ end of the other nucleic acid strand.
Unlike DNA, RNA is usually single-stranded; however, it results from DNA. RNA
needs to have complementary bases to the single strand of DNA it copies off of
(we will discuss the mechanism of RNA synthesis in Chapter 6 Molecular
Genetics). Remember, RNA contains uracil in place of thymine, which means
adenine H-bonds to uracil during RNA synthesis or in rare cases of double-
stranded RNA. Although, cytosine will still H-bond to guanine.
Note: adenine and thymine (or uracil) make two H-bonds, while cytosine and
guanine make three H-bonds.

Critical Review of Nucleic Acids:

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 Nucleic acids are polymers of nucleotides, but nucleoside triphosphates
add
In deoxyribonucleic acid DNA :
The pentose is deoxyribose (no 2’ hydroxyl)
Usually antiparallel double-strand
G=C while A T
In ribonucleic acid RNA :
The pentose is ribose (there is a 2’ hydroxyl) which makes RNA more
reactive
Usually single-stranded
G=C while A U
Biological Hypothesis and Theories
Now that we are well versed in the critical macromolecules of biological systems,
we can begin to think about biology in more conceptually. We will discuss the cell
theory (cell doctrine), the central dogma of genetics, and the RNA world
hypothesis in this section.
The cell theory has three fundamental statements:
1. All lifeforms have one or more cells
2. The cell is the most simple unit of life
3. All cells come from other cells
Scientists concluded that the cell theory should be more specific as newer
technologies allowed them to study cells in greater depth. Therefore, we now
have the modern cell theory.
The modern cell theory says that all life is composed of one or more cells, where
cells are the basic structural, functional, and organizational unit of life. Moreover,
the modern cell theory says all cells come from pre-existing, living cells via cell
division.

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 These divisions allow the genetic information (stored within cells) to pass onto
new cells, and an organism’s activity is dependent on the activity of its
independent cells. Finally, the modern cell theory says that metabolism and
biochemistry (energy flow) occur within cells, where all cells have the same
chemical composition.
Note: the cell theory does not apply to viruses because they are not living
cells.
A logical question follows from the modern cell theory. If all cells come from pre-
existing, living cells - what was the first cell? To answer that question, we first
need to understand the central dogma of genetics, which says that information
flows from DNA to RNA, and finally to proteins. In other words, DNA makes RNA,
which makes proteins.

The main implication of the central dogma of genetics is that information cannot
travel from protein to protein, or from proteins to nucleic acids (note that
information can travel from RNA to DNA, which we will discuss in later chapters).
DAT Pro-Tip: there is a particular case where information can travel from
protein to protein. Prions are misfolded proteins that cause other proteins to
misfold as well, destroying their function in the process.
As we have already seen, DNA, RNA, and proteins are essential macromolecules
to life as we know it. DNA acts as a cellular “blueprint” for storing genetic

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 information, and proteins have a multitude of functions that keep organisms alive
and well. RNA is a bit more mysterious because it acts as a messenger between
DNA and proteins; however, it can also act as a catalyst like proteins (ribozymes),
and it can store genetic information like DNA.
Now let’s go back to the question of the first cell, which we can explain with the
RNA world hypothesis. The RNA world hypothesis says that the Earth’s
“primordial soup” had a lot of RNA nucleoside triphosphates, which made
phosphodiester bonds with each other to create short strands of RNAs. As the
strands grew longer and longer, they became more and more stable.
Recall: RNA is reactive (unstable) due to the 2’ hydroxyl on the ribose sugar.
However, RNAs needed to be able to reproduce before they could have the
potential to start life. The RNA world hypothesis says that RNAs continued to
evolve until they could replicate, either on their own or with the help of other
small molecules in the primordial soup.
As the RNAs replicated and continued to become more advanced over the course
of millions of years, some RNAs may have evolved into RNA machines that were
capable of catalyzing protein synthesis. The proteins then began to affect other
processes by catalyzing a broader array of reactions - leading to more complex
molecules.
Recall that phospholipids spontaneously form bilayers when in an aqueous
environment. It is possible that phospholipids in the Earth’s early environment
formed around RNAs and proteins, giving them more favorable conditions to
evolve. As these early cell-like structures were forming, it is likely that DNA arose
as a means to store genetic information for useful proteins because the RNAs
those proteins came from were so reactive and unstable.
Now we have come full circle, developing a world where we have DNA that
reliably stores genetic information. A world where DNA converts to unstable RNA
for the creation of proteins (the central dogma of genetics). The cell theory
explains how cells became more complicated as they continued to divide, mutate,
and experience new environments.

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 Critical Review of the Biological Hypothesis and Theories:
Cells are the most simplistic unit of life, and all lifeforms have one or more of
them
Living organisms carry out their actions thanks to actions of their cells
Cells store hereditary information and arise from preexisting cells
The central dogma of genetics says that DNA makes RNA, and RNA makes
proteins
The first cell is likely to have arisen according to the RNA world hypothesis
Two central facts support the RNA world hypothesis:

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 1. RNA can store genetic information like DNA
2. RNA can catalyze chemical reactions like proteins
Amazing! Chapter 1 is done! 🎉

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