AP Biology Unit 4

●​ The Types of Signaling

The survival of a living organism depends on the ability of the cell to communicate by
sending, receiving, and responding to chemical signals. These chemical signals are called
ligands.

1)​ Autocrine signaling:

The cell secretes a ligand and this ligand then binds to a receptor on the cell that secreted
the ligand, triggering a response within that same cell. Auto means “self”, a cell signaling
itself to generate a response.
➔​ Example: cancer cells

2)​ Juxtacrine signaling:

This is signaling that depends on direct contact between the cell that is sending the
ligand and the cell that is receiving and responding to it via a surface receptor.
➔​ Example: plasmodesmata in plants (ligand travels between channels that connect
adjacent cells)
 3)​ Paracrine signaling:
The cell secretes a ligand that travels a short distance, eliciting an effect on cells in the
nearby area. These ligands are sometimes referred to as local regulators since they only
affect cells in the immediate vicinity of the cell that is sending the signals.
➔​ Example: Neurotransmitters are local regulators that travel the short distance
across a synapse to communicate with nearby cells.

4)​ Endocrine signaling:

Some ligands travel a long distance between the sending and receiving cells; this is called
endocrine signaling. Ligands that travel a long distance are called hormones.
➔​ Example: Insulin, a hormone produced and released by the pancreas, travels
through the circulatory system to trigger responses in cells all over the body.
 ●​ What are two ways that cells communicate with one another?
Cells are constantly communicating with one another. They are never really on their own;
they’re always in populations or in multicellular organisms.

-​ Direct, cell to cell communication: junction between two adjacent cells.

Molecules can pass between those two cells. This enables one cell to change the
behavior of the other.
-​ Communication via signals (ligands): A cell that’s producing a molecule,
secretes it into the bloodstream or extracellular fluid and that message is going to
be picked up by a target cell. These signals are known as ligands.
➔​ Hormones (long distance)
➔​ Local regulators (short distance)

●​ What are ligands?

They are signaling molecules in which many of them

are hormones.
-​ Binds with receptors based on complementary
shape
-​ Binding leads to a cellular response

●​ What is quorum sensing?

A kind of cell communication that’s seen in biofilm formation in bacteria (ex. films on
your teeth that can form plaque). It is how bacteria detect and respond to the density of
their population by releasing and detecting chemical signals.
 -​ Bacteria release signaling molecules
(2), that bind to cytoplasmic receptors (3)
-​ When the signal exceeds a certain
density (a quorum), genes are activated that
leads to biofilm formation

TAKEAWAY: All cells communicate

(even bacteria!)

●​ The three key phases of cell signaling

1) Reception of a ligand
2) Signal Transduction
(initial message gets changed
into another kind of message,
that can go into the cytoplasm
that often involves
amplification of the signal)
3) Cellular response

Reception:
-​ Signal molecule (ligand), binds with a receptor molecule embedded in the cell
membrane. This binding is based on complementary shape.

Transduction & Cellular response:

-​ The receptor interacts with membrane proteins to produce a second messenger.
-​ The second messenger (and other relay molecules) brings the message to
➔​ The cytoplasm (activating enzymes)
➔​ The nucleus (activating genes)
 ●​ How is the mechanism of steroid (nonpolar) hormones
different from that of water-soluble hormones?
Steroid hormones (nonpolar/hydrophobic) diffuse through the
phosplipid bilayer and from there, they can bind with cytoplasmic
receptors that forms a receptor-hormone complex (formed when
the hormone binds to the intracellular receptor). They do not
enter the cell directly, but rather bind to the receptor in the cytosol.
Then that is capable of diffusing into the nucleus where it acts as a
transcription factor (activate genes so the DNA gets made into
RNA, RNA gets made into a protein).

Water soluble (polar/hydrophilic) hormones are capable of

binding with receptors and they activate second messengers which
bring about a cellular response. These responses are quicker, but
steroid hormones are longer lasting.

●​ How is epinephrine involved in the fight or flight response?

-​ Epinephrine: AKA adrenaline
-​ Polar/water soluble (cannot diffuse into the cytoplasm, it’s going to bind at the
membrane)
-​ Through blood, epinephrine goes everywhere. However, only tissues with
receptors respond. The response differs based on tissue-type.
-​ It induces liver cells to hydrolyze glycogen into glucose in which glucose diffuses
into the blood and provides energy to fight or flee.
-​ The effect is quick and temporary, as epinephrine activates second messenger
systems (like cAMP), which trigger rapid cellular responses without needing to
enter the cell.

Reception:

A G protein is a molecular switch inside the cell that helps transmit signals from outside
the cell to the inside. When a signaling molecule (like epinephrine) binds to a G
protein-coupled receptor (GPCR), it activates the G protein by exchanging GDP for
GTP. This activation triggers a chain reaction inside the cell, leading to a specific
response (like increasing cAMP levels). Once the signal is delivered, the G protein
switches back off.
 -​ Epinephrine binds with G-protein coupled receptor
-​ The receptor changes shape on its cytoplasmic side
-​ The nearby G-protein is still bound to GDP

Reception (2) After epinephrine binds:

-​ G protein interacts with receptor
-​ By being able to interact with the receptor due to the
receptor change, it enables the G protein to interact with that
part of the receptor
-​ This discharges GDP and binds with GTP (high
energy form)
-​ Result is the G protein now becomes activated

-​ The activated G protein drifts in the membrane and binds with Adenylyl cyclase
(membrane embedded enzyme),
-​ Andenylyl cyclase converts ATP to cyclic AMP (second messenger in these G
protein coupled receptor systems)

G protein-coupled receptors (GPCRs) are cell surface receptors that detect external
signals, like hormones or neurotransmitters. When a signaling molecule binds to a GPCR,
it activates a G protein inside the cell, which triggers a cascade of events that lead to a
specific cellular response, such as the production of cAMP.
REVIEW:
1)​ Reception: Ligand (epinephrine) binds with the G protein coupled receptor
2)​ The receptor changes shape on its cytoplasmic side
3)​ This shape change allows the GPCR to interact with a G protein, causing it to
discharge GDP and bind with GTP, activating the protein
4)​ The G protein then in turn can activate Anenylyl cyclase which takes its substrate,
ATP and converts it to cAMP (the second messenger).

From transduction to response:

-​ cAMP (second messenger) activates a chain of relay molecules. These are called
kinases.
-​ This activation involves a phosphorylation cascade. One kinase activating the next
kinase, etc.
-​ The kinases are activated by phosphorylation (gaining a phosphate). Protein
phosphatase removes a phosphate.
-​ Activated kinases transfer phosphate groups to other proteins, activating them
 -​ Activated kinases phospholorylate the next kinase in the chain →
phosphorylation cascade
➔​ Protein kinase 1 acts upon protein kinase 2 by phosphorylating it, so now PK2 is
active and will activate PK3
-​ Once we get to anedylyl cyclase, each step involves multiple activations. It will
activate many cAMPs.
-​ Each of these cAMPs will start different phosphorylation chains
➔​ RESULT: Signal Amplification

-​ One epinephrine molecule activates millions of enzymes to bring about a massive

cellular response.

Turning off the response:

-​ G protein hydrolyzes GTP to GDP, inactivating itself.

-​ Inactive G protein detaches from adenylyl cyclase, stopping cAMP production.
-​ Phosphodiesterase breaks down cAMP to AMP, ending second messenger
signaling.
-​ Receptor may be inactivated or removed from the membrane to stop further
signaling.
Results:

The final step of signal transduction and the ultimate result generated by the ligand.

➔​ Examples: activation of genes by steroid hormones, the opening of ligand-gated

ion channels, and the initiation of cell processes, such as apoptosis.

Disruptions in Signal Transduction Pathways:

-​ A mutation in a gene coding for a receptor protein could result in a change in

shape of the receptor such that it would no longer be able to respond to the ligand
(cause the receptor to be unable to change shape correctly, or it might change the
shape of the receptor)
-​ When molecules in the environment interfere with a ligand’s ability to bind to its
receptor. (EX: cholera toxin binds to G-protein-coupled receptors).
-​ Mutations in the gene for adenylyl cyclase can interfere with a cell’s ability to
produce cAMP (second messenger), disrupting all steps in the signal transduction
process that are dependent on it.

●​ What is homeostasis? What are feedback mechanisms, and how do they

connect to homeostasis?
Homeostasis: The tendency of a living system to maintain its internal conditions at a
relatively constant, optimal level.
Feedback: When the output of a system is also an input. (Feeds back into the system)
➔​ Negative Feedback: Allows organisms to maintain homeostasis as they respond
to internal and external changes (temperature). Returns a system to its set point.
➔​ Positive Feedback: Can accelerate internal changes and drive a process forward
towards a conclusion.

●​ Explain how insulin promotes blood glucose homeostasis.

Negative Feedback System:
-​ In response to high blood glucose levels, the pancreas releases insulin (after eating
a sugary meal)
-​ In the liver, insulin binds at a receptor
-​ Signaling cascade → glucose transport channel to open
-​ Glucose diffuses into liver cells and gets converted to glycogen and fat for storage.
-​ Blood glucose levels will go back down, homeostasis is restored.
 ●​ Explain how insulin and glucagon maintain blood glucose homeostasis.
Above set point:
-​ Pancreas releases insulin
-​ Liver, fat, and muscle cells absorb glucose
Below set point:
-​ Pancreas releases glucagon (hormone)
-​ Liver converts glycogen to glucose

●​ Explain how blood glucose homeostasis breaks down in Type 2 Diabetes.

Normal metabolism:
-​ Insulin binds with the insulin receptor
-​ Signal cascade → glucose channel to open → glucose absorption into cells
-​ Blood glucose falls, homeostasis is restored
Type 2 Diabetes:
-​ The cells become insulin resistant
-​ Insulin binding DOES NOT lead to internal signaling (signaling cascade)
-​ Glucose channel remains closed
-​ Blood glucose stays high
-​ High blood glucose damages organs and tissues

●​ Compare and contrast Tyoe 1 and Type 2 Diabetes

Type 1:
-​ Autoimmune disorder
-​ Pancreas doesn’t produce insulin (can be treated through insulin injections)
Type 2:
-​ Insulin resistance (receptor becomes insensitive to the insulin signal)

●​ How does positive feedback work?

Positive feedback: Output of a system feeds back into the system, increasing the system’s
activity and output.
➔​ Drives a biological process (such as childbirth) to a conclusion, after which the
system shuts down.
 ●​ The Cell Cycle (Mitosis)
-​ Mitosis duplicates the chromosomes of a eukaryotic cell, transmitting that cell’s
entire genome to its daughter cells (exact clone).

-​ In multicellular organisms, mitosis is how an organism grows and repairs itself

-​ In unicellular eukaryotes (amoeba), mitosis is how reproduction occurs.

●​ What happens during the cell cycle?

-​ The cell cycle can be divided into two main

phases: Interphase (I) and Mitosis/M Phase (M)

Interphase: (cell doesn’t divide)

-​ G1 (growth phase 1): the cell increases in size
-​ S (synthesis): DNA replication/chromosome
duplication
-​ G2 (growth phase 2): growth of structures for
cell division

M phase:
-​ Mitosis: separation of chromosomes
-​ Followed by cytokinesis: division of the cell (2 cloned daughter cells of the parent
cell)
Describe the phases of mitosis:

●​ Interphase: Cell grows and replicates its DNA

●​ Prophase: Chromosomes (3) condense, the nuclear membrane (2) disintegrates,
and a spindle apparatus begins to grow at each centrosome (1)
●​ Metaphase: The spindle fibers pull each chromosome to the cell’s equator. Each
chromosome is doubled, consisting of two sister chromatids.

●​ Anaphase: Sister chromatids are pulled apart (3), and dragged to opposite ends of
the cell. Non-kinetochore microtubules cause the cell to elongate.
➔​ A kinetochore is like a handle on the chromosomes that these spindle fibers
use to pull the chromosomes apart. There are other fibers that push on one
another that causes the cell to elongate.

●​ Telophase: A new nuclear membrane (2) forms around each set of chromosomes.
The chromosomes spread out, and a nucleolus (4) appears in each nucleus.
➔​ The nucleolus disappeared during during interphase. It makes ribosomes
and ribosome production shuts down during most of mitosis.
●​ Cytokinesis: Cell splits apart into two daughter cells.
●​ Explain the importance of the G0 phase

-​ Not all cells go through the entire

cell cycle
-​ Specialized cells (like muscle and
nerve cells) leave the cell cycle and enter
into G0. (They already developed their
final form).
-​ Cells in G0 no longer divide
-​ Certain stimuli, however, can
induce a cell in G0 to reenter the cell cycle

●​ Describe the role checkpoints play in regulating the cell cycle

-​ Cell cycle checkpoints: Moments when the cell “checks” its internal conditions
and “decides” whether to progress to the next phase of the cycle. (G1,G2, and M
checkpoint)
-​ If certain molecules are in the right concentration, the cell continues through the
cycle
-​ If NOT, the cell moves into G0 or might initiate apoptosis
 ●​ What are cyclins and cyclin-dependent kinases?
Cyclins and cyclin-dependent kinases are important internal regulators of the cell cycle.
-​ Cyclins: Molecules whose concentration rises and falls throughout the cell cycle.

-​ Kinases: Molecules that activate other molecules, often by phosphorylating them.

-​ Cyclin-dependent kinases (CDKs): Kinases that respond to rising and falling
cyclin levels

-​ CDKs are present at a constant level throughout the cell cycle

-​ By contrast, the levels of cyclin rise and fall throughout the cycle
-​ When cyclin levels are high, cyclin binds to CDK to form a complex called MPF
(maturation promoting factor). It allows the cell to pass through the G2 checkpoint
and actually divide.
-​ During M phase, however, the cyclin is broken down which allows the process to
repeat in each daughter cell
●​ Cell division and cancer
-​ Cancer is caused by unregulated cell division
-​ Mutations in proto-oncogenes increase cell division by creating too many growth
factors (things that stimulate cell division)
-​ Mutations in tumor suppressor genes remove cell division inhibitors
(checkpoints).
-​ Tumor suppressor genes act like a cell’s "emergency brake" — stopping the cell
cycle if DNA is damaged or promoting apoptosis (cell death) if the damage is too
bad.
●​ Collegeboard MCQ

-​ DNA replication occurs in S phase

-​ Growth factor- things that stimulate cell division
-​ Tumor suppressor genes acts like a cell’s "emergency brake" — stopping the cell
cycle if DNA is damaged or promoting apoptosis (cell death) if the damage is too
bad. ITS BAD WHEN ITS MUTATED.
-​ the cytoplasmic domain of the insulin receptor is essential for starting the
signaling cascade inside the cell. If that part is deleted, the receptor might still bind
insulin on the outside, but it won’t be able to pass the signal inside,
-​