1. (1/11) Partner Bellringer
What is a ligand? What must a cell have in order to respond to a ligand?
What does allosteric regulation mean (remember, noncompetitive inhibitors regulate enzyme activity allosterically…)

2. 5.5: The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals
Cells on the receiving end of a signal respond in 3 steps:
Reception
Transduction
Response

3. 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals
Signals may lead to short-term (e.g., enzyme activation) or long-term (e.g., altering gene expression) responses
Signals cause responses in target cells that require a specific receptor in order to respond
Autocrine signals affect the same cells that release them
Ex: WBCs, cancer cells
Paracrine signals diffuse to and affect nearby cells
Ex: neurotransmitters
Hormones (endocrine) travel through circulation to distant cells
Ex: insulin

4. 3. Label a, b, and c as autocrine, paracrine, or endocrine (hormone)
Cell w/o receptor;
not a target cell c.

5. (1/11) Exit
Provide an example for each of the following types of signaling:
Autocrine
Paracrine
Endocrine

6. (1/12) Partner BR
Provide an example for each of the following types of signaling:
Autocrine
Paracrine
Endocrine
Some ligand receptors are located inside cells. This means that the ligand is able to diffuse directly through the phospholipid bilayer into the cell. What characteristic(s) must the ligand have in order to do this?
When we studied enzymes, protein kinases were introduced as enzymes that regulate metabolic pathways by phosphorylating other proteins. What does phosphorylation mean?

7. Local & long-distance signaling

8. Juxtacrine signaling occurs when 2 cells are in direct contact with each other (e.g., B cell activation by a helper T cell)

9. Binding of signal to receptor
causes the receptor to change
shape and become activated.
Allosteric regulation is common (non- substrate molecule binds to the allosteric site)

10. 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals
A signal molecule, or ligand, binds to a specific receptor & causes it to change shape
An inhibitor, or antagonist, can bind in place of the ligand
Ex: caffeine

11. Caffeine is a large, polar molecule that binds to receptors on nerve cells in the brain.
Its structure is similar to adenosine, which binds to receptors after activity or stress and results in drowsiness.
Caffeine binds to the same receptor, but does not activate it—the result is that the person remains alert.

12. 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals
Receptors can be classified by location or activity
Cytoplasmic receptors (intracellular) have ligands that can diffuse across the membrane into the cell
Often regulate gene expression
Ex: estrogen & testosterone
What types of molecules can diffuse thru the membrane?
Hydrophobic molecules like steroid hormones (estrogen & testosterone), NO, thyroid hormone

13. Steroid hormones and thyroid hormones diffuse into the cell and bind to intracellular receptors in the cytoplasm, nucleus, or on mitochondria.
Signal transduction leads to changes in gene expression in nucleus or metabolic activity in mitochondria

14. 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals
Membrane receptors have ligands that cannot diffuse across the cell membrane
Ion channel receptors, or gated ion channels, change shape (open) when a ligand binds
Ex: neurons release the neurotransmitter acetylcholine at a synapse with a muscle cell
Muscle cells contain ligand-gated Na+ channels with acetylcholine receptors
When acetylcholine binds to the receptors, the channels open & allow Na+ to diffuse into the cell
The influx of Na+ depolarizes the muscle cell, resulting in an action potential (electrical impulse) that then leads to a contraction

15. target cells
Neuron

18. Cyclic AMP

19. 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals
Protein kinase receptors expose or activate protein kinases in the cytoplasm
Protein kinases (enzymes) catalyze the phosphorylation of specific proteins in the following reaction:
ATP + protein  ADP + phosphorylated protein
Each protein kinase has a specific target protein in the cell that it phosphorylates
Ex: insulin receptor – binding leads to production of glucose transporters in cell
2% of our genome codes for kinases; each cell may have hundreds, each specific to its own substrate

20. Protein kinase receptors
Binding of ligand (insulin) to receptor causes a shape change, activating the receptor’s protein kinase domain in cytoplasm
Target protein is then phosphorylated by protein kinase, leading to the cellular response

21. G proteins can bind 3 molecules: The receptor
5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals
G protein-linked receptors have sites for binding to cellular proteins called G proteins
G proteins can bind 3 molecules:
The receptor
GDP/GTP (used for energy)
An effector protein
Part of the activated G protein uses GTP to activate an effector protein that converts thousands of reactants to products (amplification)
Binding of ligand (hormone) to receptor activates the receptor, which then replaces GDP with GTP on the G protein

22. Ex: adrenergic receptors involved in fight-or-flight response
G protein-linked receptors
Evolved early b/c similar among many modern organisms
Cholera, pertussis, botulism all work by producing toxins that interfere with function of receptor
60% of all meds produced today influence these pathways
Part of the activated G protein uses GTP to activate an effector protein that converts thousands of reactants to products (amplification)
Binding of ligand (hormone) to receptor activates the receptor, which then replaces GDP with GTP on the G protein

24. What type of receptor does the ligand bind to on the muscle cell?
(1/12) Exit
What is the ligand released by neurons at a synapse with a muscle cell?
What type of receptor does the ligand bind to on the muscle cell?
What happens when the ligand binds to the surface of the muscle cell?

25. (1/13) Group BR
What are 3 general types of membrane receptors? Give a specific example of each.
The following statements describe the signaling cascade stimulated by epinephrine during the fight-or-flight response. Identify which one describes distribution of the signal and which one describes amplification and explain why based on your understanding of the two words.
a. In liver cells, the binding of one molecule of epinephrine results in the secretion of 10,000 molecules of glucose into the blood.
b. The signaling cascade set off by epinephrine activates glycogen phosphorylase (an enzyme that breaks down glycogen into glucose) and inactivates glycogen synthase (an enzyme that synthesizes glycogen from glucose).

26. 5.6 Signal Transduction Allows the Cell to Respond to Its Environment
Signal transduction: a series of steps (a cascade of reactions) following signal reception that leads to a cellular response
Responses may be amplified and/or distributed by a signal transduction pathway
A second messenger is an intermediary between the receptor and the cascade of responses
Distributes a signal to allow the cell to respond in multiple ways inside the cell
Amplifies a signal by activating multiple enzymes to greatly increase the amount of product
Examples of 2nd messengers: cyclic AMP (cAMP), Ca2+
Animation for cAMP and Ca2+ second messenger pathways

27. Cyclic AMP

28. 5.6 Signal Transduction Allows the Cell to Respond to Its Environment
Signal transduction pathways involve multiple steps leading to activation or inhibition of enzymes
Ex: signal cascade in liver cells during fight-or-flight response
Inhibits glycogen synthase to prevent glucose storage as glycogen
Activates glycogen phosphorylase to break down glycogen and secrete glucose into blood

29. The Fight-or-Flight response: A Cascade of Reactions (Part 1)
Epinephrine (ligand) 1
Outside of cell
Epinephrine
(adrenergic) receptor
Activated G protein subunit
Plasma membrane
Activated adenylyl cyclase
GTP
1 epinephrine binding leads to 20 cAMP molecules being made (amplification)
ATP
cAMP 20
Inactive protein kinase A
Active glycogen synthase 20
Active protein kinase A
Inactive glycogen synthase
Inactive phosphorylase kinase
Protein kinase A inactivates glycogen phosphorylase AND activates phosphorylase kinase (distribution)
100
Active phosphorylase kinase

30. The Fight-or-Flight response: A Cascade of Reactions (Part 2)
100
Active phosphorylase kinase
Inactive glycogen phosphorylase
1,000
Active glycogen phosphorylase
Glycogen
10,000
Glucose 1-phosphate
Glucose
Inside of cell
10,000
Blood glucose
Outside of cell

31. The fight-or-flight response

32. 5.6 Signal Transduction Allows the Cell to Respond to Its Environment
Different signal transduction pathways can produce different responses to the same signal-receptor
Signal transduction ends after the cell responds
Homeostasis is maintained by the balance between regulating enzymes and signaling enzymes

33. In addition to inhibiting adenosine binding at the surface of brain cells (which ordinarily leads to drowsiness), caffeine blocks a phosphodiesterase from breaking down cAMP. How does this explain some of the other effects caffeine has on the body?
A signal can produce different responses in different cells based on the cell’s receptor. In heart and skeletal muscle cells, epinephrine leads to glucose mobilization and breakdown. But in the smooth muscles that line internal organs, respiratory passageways, and blood vessels, it leads to relaxation. How does this inhibition of smooth muscle contraction contribute to the fight-or-flight response?

34. Review
What type of receptor do the following ligands bind?
Testosterone (steroid hormone)
Acetylcholine
Insulin
Epinephrine
Provide an example for each of the following types of signaling:
Autocrine
Paracrine
Endocrine (hormone)

35. (1/14) BR: The fight-or-flight response
Outline the signal transduction pathway!
Epinephrine binds to adrenergic receptor (G protein-linked) ?
? (2 actions)
Response: exocytosis of glucose from liver cell into bloodstream

36. (1/14) BR: Fight-or-flight
What is the ligand?
What type of receptor does it bind?
What is the second messenger?
How does protein kinase A distribute the signal?
Which enzyme breaks down glycogen?
What is the cellular response?
How is this pathway an example of amplification?

37. Poster topics Research topics Toxin
Poison dart frog, Marine Cone Snails
Plant
Phototropism (auxin), Ripening (ethylene)
Immune
B-lymphocytes, T- lymphocytes
Drug
Heroin, Ecstasy
Human
Vision
Bacteria
Clostridium botulinum neurotoxin (botulism)
Disease
Diabetes/Insulin (healthy and faulty), Parkinson’s and calcium
channels (healthy and faulty)

38. POSTER TOPICS – 1st period
Phototropism
Clostridium botulinum toxin
Poison dart frogs
B-lymphocytes
Vision
Heroin
Diabetes

39. POSTER TOPICS – 7th period
Marine cone snails
Ethylene
T-lymphocytes
Ecstasy
Salmonella
Parkinson’s disease