Week 4 Flashcards
(113 cards)
1
Q
What is a ligand?
A
First messenger that binds to the receptor protein to trigger a cellular response
2
Q
What is signal transduction?
A
The biochemical mechanism responsible for transmitting extracellular signals across the membrane
3
Q
Describe the process of signal transduction?
A
- First messenger binds to receptor proteins
- Activation of upstream signaling proteins signal second messengers
- Second messengers migrate to the downstream signaling proteins
- Downstream proteins bind to target proteins activating it
4
Q
What processes activate a particular response?
A
- Covalent protein modifications
- Protein conformational changes
- Altering the rate of gene expression
5
Q
What are the general steps of chemical messengers?
A
- The chemical messenger (ligand) is secreted from a specific cell in response to a stimulus
- The chemical messenger diffuses or is transported through blood or ECF to the target cell
- Hydrophobic message diffuses across the plasma membrane and binds to an intracellular receptor and elicits a response
- The receptor on the target cell membrane specifically binds the messenger
- Binding of the messenger to the receptor elicits a response
- The signal is terminated
6
Q
What are the 4 intracellular communications by chemical mediators?
A
- Gap junctions
- Synaptic
- Paracrine and autocrine
- Endocrine
7
Q
Describe transmission, localization, and specificity dependence of gap junctions
A
- Directly transmitted from cell to cell
- Localized
- Anatomic location
8
Q
Describe transmission, localization, and specificity dependence of the synaptic
A
- Transmitted across synaptic cleft
- Localized
- Anatomic location and receptors
9
Q
Describe transmission, localization, and specificity dependence of paracrine and autocrine
A
- Transmission by diffusion in interstitial fluid
- Locally diffused
- Dependence on receptors
10
Q
Describe transmission, localization, and specificity dependence of endocrine
A
- Transmission by circulating body fluids
- Generalized
- Dependence on receptors
11
Q
What are the primary messengers of the body?
A
Ligands
12
Q
What are the secondary messengers of the body?
A
- cAMP
- cGMP
- Diacylglycerol (DAG)
- IP3
- Ca2+
13
Q
What is the function of secondary messenger?
A
To amplify receptor-generated signals
14
Q
Describe the steps of signal amplification of Glucose 1-P
A
- Second messengers amplify the signal that is initiated by a primary messenger
- Receptor activation of Adenylate cyclase generates cAMP
- cAMP binds to a downstream signaling protein Protein Kinase A (PKA)
- PKA then phosphorylates enzyme 2 which then phosphorylates enzyme 3
- Low concentration of signal in the environment, even a single molecule, can cause a large intracellular signal and response
15
Q
Describe the steps of signal amplification of PLC
A
- PLC controls the activiyt of the second messengers (IP3, DAG and Ca2+)
- PLC hydrolyzes PIP2 into IP3 and DAG
- DAG activates Protein Kinase C (PKC)
- IP3 activates Ca2+ channels in the ER leading to increased cyctoplasmic levels to Ca2+
- Ca2+ can then activate Ca2+ binding proteins like calmodulin
16
Q
Describe the function of cell-surface receptors
A
Bind to membrane receptors because they cannot rapidly cross the membrane
17
Q
What are the ligands associated with cell-surface receptors?
A
Polar molecules
18
Q
Describe the function of intracellular receptors
A
Gene-specific transcription factors that is able to diffuse through the membrane to bind to intracellular receptor
19
Q
What are gene-specific transcription factors?
A
Protein that binds to a specific site on DNA and regulates the rate of transcription of a gene
20
Q
What are the ligands associated with intracellular receptors?
A
Hydrophobic messengers
21
Q
How are lipophilic hormones transported in the blood?
A
- Bound to serum albumin
- Bound to steroid hormone-binding globulin (SHBG)
- Bound to thyroid hormone-binding globulin (TBG)
22
Q
How do steroids enter the cell?
A
Simple diffusion across the plasma membrane
22
Q
How do steroids enter the cell?
A
Simple diffusion across the plasma membrane
23
Q
How do thyroid hormones enter the cell?
A
Facilitated diffusion
24
Describe the regulation process of hormonal transcription
1. Hormone is carried on serum binding proteins that diffuse across the plasma membrane and bind to specific receptor proteins in nucleus
2. Hormone changes conformation of receptors
3. Binds to specific regulatory regions called hormone response elements
4. Receptor attracts coactivators and corepressor proteins that regulates transcription by increasing or decreasing rate of mRNA formation
5. Hormone-regulated gene product produces the cellular response to the hormone
25
Where is glucocorticoid receptor located?
1. Cytosol bound to heat shock proteins (HSP)
2. When cortisol binds the GR, the GR dissociates from HSP exposing a nuclear localization signal (NSL)
3. GR homodimerizes and translocates to the nucleus where it binds to hormone response elements (HRE) in the DNA
4. Activate transcription of genes and inhibit transcription of other genes to regulate metabolism
26
Is the glycocoticoid receptor host a rapid process?
No, because you need to complete the process in order to have a response
27
What does an activated GR do once it enters the nucleus?
It homodimerizes and translocates to bind to HRE
28
What common features do membrane receptors share?
1. Extracellular domain that binds the chemical messenger
2. 1 or more membrane-spanning domains that are a-helices
3. Intracellular domain that initiates signal transduction
29
How do membrane receptors transmit a signal?
1. Ligand binding to extracellular domain of the receptor causes a conformational change communicated in the intracellular domain
2. Activated intracellular domain initiates a signal transduction pathway
30
Is the signal pathway multidirectional?
It moves in one direction
31
List the 3 effects on the cell when membrane receptors achieves signal transduction
1. Rapid and immediate effects of cellular ion concentration
2. Activation or inhibition of enzymes
3. Slower changes in the rate of gene expression for a specific set of proteins
32
List the 3 common membrane receptors
1. G protein-coupled receptor
2. Receptor enzymes (kinases)
3. Gated-ion channels
33
What is GPRC?
a-helical integral membrane proteins that make 7 passes through the membrane
34
What sensory responses are associated with GPRC?
Vision, taste, and smell
35
What are the 3 proteins comprising G-proteins
1. G-alpha
2. G-beta
3. G-gamma
36
What are the 3 G-alpha proteins?
- Gs-a
- Gi-a
- Gqa
37
What is Gs-a?
Stimulatory protein that activates adenylate cyclase
38
What is Gs-a’s second messenger?
cAMP
39
What is Gi-a?
Inhibitory protein that inhibits adenylate cyclase
40
What is Gq-a?
Stimulatory protein that stimulates phospholipase C (PLC)
41
What is Gq-a’s second messenger?
IP3, DAG, Ca2+
42
What do G-beta and G-gamma do?
1. Stimulates phospholipase A
2. Regulate ion channels
3. Regulate receptor kinases
43
What binds G proteins together?
GTP
44
Where is G-alpha and G-gamma located?
Inner plasma membrane leaflet
45
What occurs when a signal is transmitted through the GPCR?
Causes a conformation change in GPCR leading an exchange of GDP for GTP in the Ga protein
46
Describe the process of self-inactivation in G-protein signaling
1. Gs with GDP bound is turned off and can’t activate adenylyl cyclase
2. Contact of Gs with hormone-recpetor complex causes displacement of bound GDP by GTP
3. Gs with GTP bound dissociates into a and by subunits. Gsa-GTP is turned on activating adenylyl cyclase
4. GTP bound to Gsa is hydrolyzed by the protein’s intrinsic GTPase; Gsa turns itself off. The inactive a subunit reassociates with the by subunit.
47
Describe the process of inactivation by Gi-alpha
1. When bound to GTP, Gi is in its active form
| 2. G-GTP inhibits the activation of adenylyl cyclase
48
What are 3 distinct pathways for ligands (primary messengers) to alter transcription?
1. Steroid and thyroid hormones
2. Activation of protein kinases in cytosol that move to the nucleus
3. Activation of latent transcription factors in the cytosol
49
How does epinephrine interact with the cell via GPCR?
1. Epinephrine is a hormone made in adrenal glands
2. Mediates stress response by the mobilization of energy
3. Binds to receptors in muscle or liver cells to induce breakdown of glycogen
4. Binds to receptors in adipose cells induces lipid hydrolysis
5. Binds to receptors in heart cells increases heart rate
50
Is the epinephrine cascade a fast process?
Yes
51
Explain the process of GPCR using secondary molecules for hormonal responses?
1. Hormone binds to a specific receptor
2. The occupied receptor causes GDP-GTP exchange on Gqa
3. Gqa with bound GTP, moves to PLC and activates it
4. Active PLC cleaves PIP2 to IP3 and diacylglycerol
5. IP3 binds to a specific receptor-gated Ca2+ channel, releasing sequestered Ca2+
6. Diacylglycerol and Ca2+ activate protein kinase C at the surface of the plasma membrane
7. Phosphorylation of cellular proteins by protein kinase C produces some of the cellular responses to the hormone
52
What are functions of 5 secondary messengers?
```
PIP2
PLC
IP3
DAG
GPCR
```
53
What is PIP2?
Phospholipid that is attached to the inner leaflet of the membrane
54
What is PLC?
Cleaves PIP2 into IP3 and DAG
55
What is IP3?
Diffuse through the cytosol and binds to a ligand gated ion channel on the ER to cause Ca2+ ion release (hydrophilic)
56
What is DAG?
Remains embedded in the membrane and can bind to and activate PKC (hydrophobic)
57
What is GPCR?
Activates IP3 which can activate a ligand-gated ion channel
58
Describe how growth factors signal through tyrosine kinase residues
1. Ligand binding, receptor dimerization, and kinase activation
2. Phosphorylation of RTK cytoplasmic tailes
3. Protein binding to RTK phosphotyrosines and phosphorylation of target proteins
4. Activation of downstream signaling pathways
59
Describe the 2 step process of epidermal growth by TK and growth factor signaling?
1. EGF binding induces dimerization and EGFR1 phosphorylation of EGFR2 Tyr residues
2. Conformational change leads to EGFR2 phosphorylation of EGFR1 Tyr residues
60
Explain the steps of EGF Signaling Pathway
1. Recruitment of RAF of the membrane by RAS-GTP
2. Src phosphorylation of Raf
3. Raf phosphorylation of MEK
4. MEK phosphorylation of ERK
5. Nuclear translocation of phosphorylated ERK
6. Regulation of gene expression by ERK homodimer
61
Explain the process of cell growth due to growth factors
1. Growth factor activates MAPK
2. It leads to phosphorylation of Jun and Fos in nucleus
3. The activity of the transcription factor E2F promotes synthesis of several enzymes essential for DNA synthesis
62
Describe the Serine-Threonine Kinase Receptors binding to TGF-b
1. TGF-B binds to type II receptor
2. Type II receptor phosphorylates type I receptor
3. Activated type I receptor phosphorylates R-Smad
4. R-Smad complexes with Co-Smad and migrates to nucleus
63
Describe the JAK-STAT Pathway inhibition by Toficitinib
1. JAK inhibitor interferes with JAK STAT pathway
2. Inhibitor binds to JAK proteins preventing phosphorylation of STAT
3. STAt must be phosphorylated and dimerize before it can enter the nucleus acting as a transcription factor activating the gene transcription of numerous cytokines
4. Blocks the activity of JAK3 and JAK1
64
What are the triggers for ion-channel pathways?
1. Changes in the membrane potential
| 2. Ligand binding to specific receptor sites
65
What are the roles of ion-channel receptors in regards to the nervous system?
1. Voltage-gated sodium channels
2. Nicotinic acetylcholine receptor
3. Ionotropic glutamate receptor
4. Gamma aminobutyric acid receptor A
66
What is the voltage inside the cell?
-50 to -70mV
67
How many ions are transferred by Na+K+ ATPase?
1. 3 Na+ (out)
| 2. 2K+ (in)
68
Explain the process gated channels in nerve signaling
1. Depolarization
2. Repolarization
3. Secretory vesicles containing acetylcholine
4. Excretion to the synaptic cleft
5. Na+ and Ca2+ binds acetylcholine receptor ion channels
6. Action potential occurs
69
Give a brief explanation of nicotinic acetylcholine receptors
1. Before ACh is released, it is sequestered in vesicles located near an active zone in the presynaptic membrane.
2. Presynaptic membrane also has voltage-gated Ca2+ channels that open when the action potential reaches them, resulting in an influx of Ca2+.
3. Ca2+ triggers fusion of the vesicles with the plasma membrane, and ACh is released into the synaptic cleft.
4. Ach binds to nicotinic acetylcholine receptors on muscle cell and causes a conformational change.
5. Na+ and K+ to flow across the membrane leading to depolarization.
70
What are the methods of signal termination?
1. Removal of stimulus
2. Removing phosphate groups by phosphatases
3. GTPases breakdonw G proteins
4. Phosphodiesterses degrade cAMP
71
In what ways does living organisms require energy?
1. Performing mechanical work
2. Active transport of molecules and ions
3. Synthesis of macromolecules and biomolecules
4. Biosignaling
72
What is metabolism?
The reactions of energy extraction and energy use
73
Describe the process of metabolic pathways
1. Molecules are degraded or synthesized stepwise in a series of linked reactions called metabolic pathways.
2. ATP is the energy currency of life.
3. ATP can be formed by the oxidation of carbon fuels.
4. Although there are many metabolic pathways, there are a limited number of reaction types involving particular intermediates that are common to too many pathways.
5. Metabolic pathways are highly regulated.
74
What are 2 criterias in constructing a metabolic pathway?
1. Individual reactions must be specific
- Facilitated by enzymes
- Only yields a specific product
2. The overall pathway must be thermodynamically favorable
75
What is catabolism?
Convert energy from fuels into useful cellular energy
76
What is anabolic?
Reactions that require energy genrating complex structures
77
What is the term for a pathway that is both anabolic and catabolic?
Amphibolic pathways
78
What is the first law of thermodynamics?
1. Energy cannot be created or destroyed.
| 2. Energy can be converted from one form to another, but the total energy in a system remains constant
79
What is the second law of thermodynamics?
In the process of transforming energy, living organisms must increase entropy of the universe
80
What is ΔH?
Enthalpy: heat content
81
What is ΔS
Entropy
82
What does it mean to be exergonic?
Negative ΔG where energy is released
83
What does it mean to be endergonic?
Positive ΔG where energy is absorbed
84
What influences endergonic reactions?
1. Allosteric effectors
| 2. Removing product and using it as a substrate for another reaction
85
What can indicate the direction of a reaction?
Free energy: ΔG
86
What can determine the speed of a reaction?
Enzymes
87
Describe the relationships between Keq and ΔG
1. Keq is greater the than 1, ΔG is negative proceeding the reaction forward
2. Keq is 1, ΔG is 0 and reaction is equilibriated
3. Keq is less than 1, ΔG is positive proceeding the reaction is reverse
88
What is a high energy bond?
Any bond that can be hydrolyzed to release more or the same amount of energy as ATP
89
What are examples of high energy molecules?
1. GTP: protein synthesis
2. CTP: lipid synthesis
3. UTP: combining sugars
4. ATP: transport, mechanical work
90
Are high energy bonds stable?
Unstable
91
Describe the structure of ATP
1. Adenine
2. Ribose
3. Triphosphate unit
92
What are bonds between phosphate group in ATP called?
Phosphoanhydride bonds
93
What is the more stable form of ATP?
ADP and Pi
94
Why is the hydrolysis of ATP exergonic?
The triphosphate unit contains phosphoanhydride bonds that are unstable
95
Describe the transferring of ATP
1. The attachment of a part of ATP molecule to substrate or aa residue in enzyme
2. Detachment and release adduct with Pi or PPi attached
96
What is the purpose for Mg2+ in ATP hydrolysis?
Shields the negative charges and influences the conformation of phosphate groups
97
What is a coenzyme?
Nonprotein substance that takes part in an enzymatic reaction and is regenerated at the end of the reaction
98
What is generated from fuel oxidation energy during bodily processes?
Reduced coenzymes
99
What are examples of coenzymes?
1. NADH
2. NADPH
3. FADH2
100
What coenzymes assist the generation of ATP during oxidative phosphorylation?
NADH and FADH2
101
What is the purpose of fuel oxidation?
1. Major source of ATP
| 2. Means of transferring energy from chemical bonds to cellular processes
102
What is equal with the amount of energy from fuel?
The amount of heat generated when fuel is burned
103
What is cellular respiration?
Transforms energy from chemical bonds of fuels into the reduction state of electron accepting coenzymes such as NAD+ and FAD
104
What is considered a derivative of niacin?
NAD+
105
What is NAD+ and FAD used for?
Sources of electrons for ATP synthesis
106
What is a derivative of riboflavin?
FAD
107
What is the structure and function of CoA-SH?
A coenzyme that contains vitamin B5 and a sulfhydral group that acts as a carrier of acetyl groups
108
How many ATP does NAD+ and FAD produces?
2.5 and 1.5, respectively
109
Differentiate oxidation and reduction
Oxidation losses electrons, reduction gains electrons
110
What does it mean when a carbon is more reduced?
More free energy is released upon oxidation
111
Why is fat an efficient fuel source than glucose?
It's more reduced
112
Explain the extraction of energy from food
1. Large molecules in food are broken down into smaller units
2. Small molecules can be converted into acetyl-CoA
3. ATP is produced from the oxidation of acetyl-CoA
4. NADH and FADH2 are oxidized and transfer their electrons to O2 generating a proton gradient when producing ATP
