1
Q
Cellular signal transduction cassettes detect, amplify, and integrate external signals comprised of:
A
- Specific cell surface membrane receptors
- Effector signaling elements
- Regulatory proteins
2
Q
Six steps of signaling
A
- Synthesis of the signaling molecule (ligand)
- Release of the signaling molecule (ligand)
- Transport of signaling molecule to target cell
- Binding of the ligand by a specific receptor protein and CHANGE in conformation
- Change in cellular metabolism, function, or development - cellular response
- Removal of ligand, terminating cellular response
- Degradation of ligand
3
Q
Define hormones
A
Chemical messengers made by endocrine cells and secreted into the blood
4
Q
T/F: Hormones affect gene expression and protein synthesis
A
True
5
Q
Autocrine hormones
A
Act on the same cell that they were secreted from
6
Q
Paracrine hormones
A
Act on other cells
7
Q
Types of hormones
A
- Steroids
- Amine (amino acid derived)
- Peptide (lumped with polypeptides)
- Polypeptides
8
Q
3 Cholesterol Precursors:
A
- Corticosteroids
- Androgens
- Estrogens
9
Q
What do steroids immediately do?
A
Diffuse out of endocrine cells into the blood
10
Q
Are steroid hormones lipid soluble?
A
Yes. They can cross cell membranes.
11
Q
Where are the steroid hormone receptors?
A
Intracellular (cytoplasmic) receptors are located inside target cells
12
Q
Steroid hormones have a _____ (longer/slower) acting, _____ (longer/slower) half-life than peptide hormones.
A
Slower Acting
Longer half-life
13
Q
How do steroid hormones lead to signal cascades?
A
- Hormone diffuses into cell
- Activated receptor hormone complex alters gene expression
- New mRNA directs synthesis of certain proteins to ribosomes
- New proteins alter cell activity
14
Q
What are Amine hormones derived from?
A
Tryptophan and Tyrosine
15
Q
Where are amine hormones stored until they’re secreted?
A
In endocrine cells
16
Q
Where are amine hormone receptors located?
A
Can be located on the cell surface or intracellular
17
Q
Do polypeptide hormones immediately enter the blood?
A
No. They can be stored in endocrine cell vesicles
18
Q
Polypeptide hormones are ___ soluble
A
Water
19
Q
Do polypeptide hormones readily pass through the cell membrane?
A
No
20
Q
What are polypeptide hormones also called?
A
First messengers - they bind to external receptors
21
Q
Intracellular effects are mediated by
A
Second messengers
22
Q
Second messengers are ____ (low/high) weight signaling molecules such as:
A
Low molecular weight
Cyclic adenosine monophosphate (cAMP) or Calcium
23
Q
G-protein coupled receptors are ___ ___ proteins
A
Integral membrane proteins (extracellular N-terminus)
24
Q
G-protein coupled receptors have ___ (#) transmembrane-spanning alpha-helices (ligand binds to pocket)
A
7
25
G-protein coupled receptors have ___ (#) extracellular and intracellular loops.
3 - the third intracellular loop recruits G-proteins
26
G-protein coupled receptors have an intracellular ___-____ ____ ____
C-terminal tail membrane
27
Do G-protein coupled receptors have intrinsic catalytic domains?
No
28
G-protein (guanine nucleotide-binding) activates:
Adenylyl cyclases (converts ATP to cAMP). It also activates protein kinases in the cytosol (signal cascade)
29
Phosphodiesterase inactivates
cAMP (turns off cell response)
30
Specificity of a G-protein is conferred by the ___-____, which contains the GTP-binding site and an ___ ____ activity
Conferred by the alpha-subunit which contains the GTP-binding site and an intrinsic GTPase activity
31
Adenylyl cyclase is activated by:
The action of the alpha-subunit of the G-protein (Gs)
32
With adenylyl cyclase, each molecule of bound hormone can stimulate many Gs alpha-subunits that amplifies the:
Original hormone signal
33
2 Bacterial toxins that target G-proteins:
1. Cholera toxin
| 2. Pertussis toxin (whooping cough)
34
With Cholera toxin, what does ADP do?
Ribosylates Gs alpha subunit
35
With Cholera toxin: An increase in ____ within the intestinal epithelial cells leads to _____ of Cl- channels and efflux of ___ and ___ (____ ____).
With Cholera toxin: An increase in cAMP within the intestinal epithelial cells leads to phosphorylation of Cl- channels and efflux of electrolytes and water (severe diarrhea).
36
With Pertussis toxin, what does ADP do?
Ribosylates Gs alpha subunit
37
With Pertussin toxin: The enhanced ____ levels inhibit ___ functions
Enhanced cAMP levels inhibit neutrophil
38
Do Tyrosine kinase-linked receptors have intrinsic enzymatic activity?
No
39
With Tyrosine kinase-linked receptors: Ligand binding forms a ____ that activates ___ ____ to phosphorylate downstream targets (signal cascade)
Ligand binding forms a dimer that activates tyrosine kinases
40
Intrinsic enzymatic activity receptors are ____-triggered protein _____
Ligand-triggered protein kinases
41
Intrinsic enzymatic activity receptors are similar to:
Tyrosine-linked receptors (form dimers upon ligand binding)
42
With Intrinsic enzymatic activity receptors: Ligand/receptor complex directly acts as a ___ ___
Tyrosine kinase (phosphorylates other kinases)
43
With Intrinsic enzymatic activity receptors: Phosphorylation activates _____
Other protein kinases
44
In ion-channel receptors, ___ binding changes confirmation of the receptor
Ligand
45
Ligand binding in ion-channel receptors allows for:
Specific ions (sodium, potassium) to flow through the channel.
46
___ ___ prevents the release of acetylcholine neurotransmitter and cleaves proteins involved in docking of neurotransmitter vesicles
Botulinum toxin
47
Cells maintain steep intracellular (____)/extracellular (___) Calcium concentration gradient that enables rapid changes in Calcium concentration via __ ___
100nM
1mM
Hormone ligation
48
Calcium binds to ___ protein, inducing conformational change
Calmodulin
49
Calmodulin protein is __ __ __ joined by a long __ __
2 globular domains
long alpha helix
50
Calcium/calmodulin complex binds to and modifies __ __ that initiate __ __
Target proteins (kinases)
Signal cascade
51
________ is the second messenger responsible for calcium mobilization
Phosphatidylinositol 4,5-bisphosphate (PIP2)
52
PIP2 is hydrolyzed by a __ __ __ __ (PLC) to generate 2 second messengers
PIP2 Specific Phospholipase C
53
The 2 second messengers generates by hydrolyzed PIP2
Inositol triphosphate (IP3)
Diacylglycerol (DAG)
54
IP3 is __ soluble and it mobilizes ___
Water
Calcium
55
DAG is anchored in the plasma membrane due to:
Hydrophobic fatty acid side chains
56
DAG activates:
Key protein kinase C (PKC) family
57
_____ can be hydrolyzed to other phospholipases to produce other lipid second messengers
Phosphatidylcholine
58
Second messengers produced by hydrolyzed Phosphatidylcholine
1. Different species of DAG
2. Phosphatidic acid
3. Arachidonic acid
59
Species of DAG are generated by
PLC
60
Phosphatidic acid is generated by
PLD
61
Arachidonic acid is generated by
PLA2
62
__ __ and __ are key inflammatory and pain mediators
Arachidonic acid and prostaglandins
63
Arachidonic acid and prostaglandins are precursors of
Eicosanoids
64
4 Eicosanoids
1. Prostaglandins
2. Prostacyclins
3. Thromboxanes
4. Leukotrienes
65
Eicosanoids act like ___ and signal via:
Hormones
G-protein coupled receptors
66
Arachidonic acid and prostaglandins modulate
1. Smooth muscle contraction
2. Platelet aggregation
3. Gastric acid secretion
4. Salt and water balance
67
Arachidonic acid conversion to prostaglandins involves a ___ ___
Cyclooxygenase isoform
68
2 cyclooxygenase isoforms
COX-1 (constitutive) and COX-2 (response to inflammatory mediators)
69
COX-1 and COX-2 roles:
1. Stimulate inflammation
2. Regulate blood flow to organs such as the kidney
3. Control ion transport across membranes
4. Modulate synaptic transmission
5. Induce sleep
70
Example of cyclooxygenase inhibitors
Nonsteriodal anti-inflammatory drugs (NSAIDs)
Aspirin and Ibuprofen
71
Role of cyclooxygenase inhibitors
Block cyclooxygenase conversion to prostaglandins
72
___ irreversibly inactivates both forms
Aspirin
73
Selective inhibitors of ___ are effective treatments for inflammatory conditions (rheumatoid arthritis)
COX-2
74
Arachidonic acid is also converted to leukotrienes by ___
Lipoxygenases
75
Explain receptor-independent signaling
Low molecular weight signaling molecules that cross the plasma membrane and directly modulate the activity of the catalytic domains of transmembrane receptors or cytoplasmic signal transducing enzymes
76
__ __ stimulates guanylate cyclase (generates cGMP (relaxes blood vessels))
Nitric oxide
77
Angina symptoms treated with __ __, which is converted to __ __
Glyceryl Trinitrate
Nitric Oxide
78
Explain endocytosis
Packaging of extracellular materials in vesicles at the cell surface
79
Endocytosis requires __
ATP
80
3 types of endocytosis
1. Pinocytosis
2. Phagocytosis
3. Receptor-mediated endocytosis
81
Pinocytosis is cell __
Drinking
82
Pinocytosis is the:
Nonspecific absorption of extracellular fluid
83
Explain how pinocytosis works
Membrane caves in, then pinches off into the cytoplasm as pinocytotic vesicle
84
Phagocytosis is cell __
Eating
85
Phagocytosis is activated by attachment to:
Pathogen-associated molecular patterns (PAMPS)
86
Receptor-mediated endocytosis is __
Selective
87
Receptor-mediated endocytosis forms ___ at ___
Vesicles (containing receptors)
The surface of the membrane
88
Receptor-mediated endocytosis has ___ coated vesicles (forms polyhedral lattice)
Clathrin
89
An example of receptor-mediated endocytosis is
Iron transport via transferring receptor
90
Transcytosis is the:
Movement of receptors to a different membrane from the one in which it was endycytosed
Biochemistry
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