G-Protein coupled receptors and regulation of glycogenolysis Flashcards

1
Q

What is the enzyme that breaks down glycogen into glucose 1-phosphate

A

Glycogen Phosphorylase

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2
Q

How is glucose 1-phosphate converted into glucose 6-phosphate?

A

By the enzyme phosphoglucomutase

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3
Q

What are the 3 main main fates of glucose 6-phosphate?

A

Glycolysis for energy production
Pentose phosphate pathway for biosynthesis and redox balance
Conversion to glucose(in the liver) for release into the blood.

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4
Q

What is the enzyme that breaks down glycogen into glucose 1-phosphate?

A

Glycogen phosphorylase.

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5
Q

How is glucose 1-phosphate converted into glucose 6-phosphate?

A

By the enzyme phosphoglucomutase.

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6
Q

What are the three main fates of glucose 6-phosphate?

A

Glycolysis for energy production.
Pentose phosphate pathway for biosynthesis and redox balance.
Conversion to glucose (in the liver) for release into the blood.

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7
Q

In glycolysis, what does glucose 6-phosphate eventually break down into under aerobic conditions?

A

Pyruvate, which further produces CO₂ and H₂O via the citric acid cycle and oxidative phosphorylation.

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8
Q

What is produced when glucose 6-phosphate enters glycolysis under anaerobic conditions?

A

Lactate.

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9
Q

What are the two key products of the pentose phosphate pathway?

A

Ribose-5-phosphate (for nucleotide synthesis).
NADPH (for fatty acid synthesis and maintaining redox balance).

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10
Q

What liver-specific enzyme converts glucose 6-phosphate into free glucose?

A

Glucose 6-phosphatase.

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11
Q

Why is glucose 6-phosphate considered a metabolic crossroad?

A

It links energy production (glycolysis), biosynthesis (pentose phosphate pathway), and blood glucose regulation (liver glucose release).

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12
Q

What is the primary purpose of NADPH produced in the pentose phosphate pathway?

A

To provide reducing power for fatty acid synthesis and maintain cellular redox balance by reducing glutathione.

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13
Q

How does glucose 6-phosphate contribute to maintaining blood glucose levels?

A

In the liver, glucose 6-phosphatase converts it to free glucose, which is released into the blood for other tissues.

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14
Q

What is neuronal signaling?

A

A process where neurons transmit signals via nerve impulses and release neurotransmitters to communicate with target cells.

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15
Q

How are neurotransmitters released in neuronal signaling?

A

Nerve impulses (action potentials) trigger the release of neurotransmitters into the synaptic cleft.

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16
Q

What are two main target cell responses in neuronal signaling?

A

Muscle contraction (e.g., skeletal or smooth muscles).
Secretion (e.g., glands releasing hormones or enzymes).

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17
Q

What is the typical signaling distance in neuronal signaling?

A

Short-range (micrometers to millimeters), across synapses.

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18
Q

What is endocrine signaling?

A

A process where endocrine glands release hormones into the bloodstream, which travel to distant target cells.

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19
Q

How do hormones reach their target cells in endocrine signaling?

A

Hormones are released into the bloodstream and circulate through the body to bind to specific receptors on target cells.

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20
Q

What are two key target cell responses in endocrine signaling?

A

Metabolic changes (e.g., insulin promoting glucose uptake).
Long-term physiological adjustments (e.g., growth or stress response).

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21
Q

What is the typical signaling distance in endocrine signaling?

A

Long-range (centimeters to meters), as hormones travel through the bloodstream.

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22
Q

Which signaling mechanism is faster, neuronal or endocrine?

A

Neuronal signaling is faster (milliseconds) compared to endocrine signaling (seconds to minutes or longer).

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23
Q

How does the specificity of neuronal signaling compare to endocrine signaling?

A

Neuronal signaling is highly specific, targeting individual cells via synapses.
Endocrine signaling is less specific, affecting all cells with matching hormone receptors.

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24
Q

Give an example of neuronal signaling in the body.

A

Muscle contraction or sensory reflexes.

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25
Give an example of endocrine signaling in the body.
Blood glucose regulation by insulin from the pancreas.
26
What is glycogenolysis?
Glycogenolysis is the process by which glycogen, a stored form of glucose, is broken down into glucose for energy use.
26
What is epinephrine?
Epinephrine is a hormone that is released in response to stress, such as exercise or fear.
26
What is glycogen phosphorylase?
Glycogen phosphorylase is the enzyme that breaks down glycogen into glucose-1-phosphate.
26
What is phosphorylase kinase?
Phosphorylase kinase is an enzyme that phosphorylates and activates glycogen phosphorylase.
27
How is glycogen phosphorylase regulated?
Glycogen phosphorylase is regulated by calcium ions (Ca2+). When Ca2+ levels are high, glycogen phosphorylase is more active.
27
What is the epinephrine-mediated mechanism of glycogenolysis?
The epinephrine-mediated mechanism of glycogenolysis is a complex process that is regulated by a number of factors, including epinephrine, Ca2+, and phosphorylation. This process is important for providing the body with energy during times of stress.
28
What are G protein-coupled receptors(GPCRs)?
GPCRs are a large family of cell surface receptors that play a key role in signal transduction by tranmitting extracellular signals into the cell.
29
How many transmembrane domains do GPCRs have, and what are they made of?
GPCRs have 7 transmembrane a-helicases made of 22-24 hydrophobic amino acids, anchoring them in the cell membrane
30
What is the role of the extracellular regions of GPCRs?
The extracellular regions are involved in ligand( signal molecule) binding.
31
What is the role of the intracellular loops of GPCRs?
Intracellular loops facilitate intraction with G-proteins, specifically the loops between TM5/TM6 and TM3/TM4.
32
What are the N-terminus and C-terminus of GPCRs?
The N-termimus is located extracellularly,and the C-termminus is located intracellularly.
33
What happens when a ligand binds to a GPCR?
Ligand binding causes a conformational change in the receptor, activating its associated G-protein
34
What are the components of the heterotrimeric G-protein complex?
The G-protein complex has three subunits: Gα, Gβ, and Gγ.
35
What happens to the G-protein in its inactive state?
In the inactive state, the Gα subunit is bound to GDP (guanosine diphosphate).
36
How is the G-protein activated?
Upon ligand binding, the Gα subunit exchanges GDP for GTP, causing it to dissociate from the Gβγ dimer.
37
What happens after the G-protein is activated?
The Gα subunit and the Gβγ dimer activate downstream signaling pathways, leading to cellular responses such as enzyme activation or ion channel modulation.
38
What is an example of a GPCR, and what does it regulate?
The β-adrenergic receptor is a GPCR that binds epinephrine and regulates functions like heart rate and energy mobilization.
39
What does GDP-to-GTP exchange in G-proteins signify?
It signifies G-protein activation, which triggers intracellular signaling cascades.
40
What do G proteins bind to regulate their activity?
G proteins bind GTP (guanosine triphosphate) and GDP (guanosine diphosphate) to regulate their activity.
41
What is the structure of G proteins?
G proteins are heterotrimeric, composed of three subunits: α subunit (45 kD): Binds GDP/GTP and has intrinsic GTPase activity. β subunit (35 kD): Forms a stable complex with the γ subunit. γ subunit (7 kD): Closely interacts with the β subunit.
42
To which protein superfamily do G proteins belong?
G proteins belong to the GTPase superfamily, which hydrolyzes GTP to GDP.
43
What is the active state of a G protein?
The active state occurs when the α subunit binds GTP, allowing the α subunit and βγ dimer to interact with downstream effectors.
44
What is the inactive state of a G protein?
The inactive state occurs when the α subunit binds GDP, and the three subunits remain tightly associated.
45
What role do G proteins play in signal transduction?
G proteins act as molecular switches, relaying signals from GPCRs to downstream targets like enzymes (e.g., adenylate cyclase) and ion channels.
46
What physiological processes do G proteins regulate?
G proteins regulate processes such as metabolism, growth, and sensory perception.
47
What is the general sequence of events in signal transduction?
Signal (ligand binding). Reception (ligand-receptor interaction). Amplification (signal strength increases). Transduction (intracellular signaling cascade). Response(s) (cellular changes).
48
What role does epinephrine play in signaling?
Epinephrine acts as a ligand (first messenger) that binds to the β-adrenergic receptor, triggering a cascade of intracellular signaling events.
49
What happens when epinephrine binds to the β-adrenergic receptor?
The receptor undergoes a conformational change, becoming activated and initiating downstream signaling via G-proteins.
50
What is the role of G-proteins in the epinephrine pathway?
G-proteins bind GDP in their inactive state. When activated, GDP is exchanged for GTP on the Gα subunit. The Gα subunit dissociates to activate downstream effectors like adenylyl cyclase.
51
What is the function of adenylyl cyclase in this pathway?
Adenylyl cyclase converts ATP to cAMP, which acts as a second messenger to amplify the signal.
52
How does cAMP contribute to the signaling cascade?
cAMP activates protein kinase A (PKA), which phosphorylates target proteins, leading to various cellular responses.
53
How is the epinephrine pathway an example of signal amplification?
One epinephrine molecule activates multiple receptors. Each receptor activates many G-proteins. Adenylyl cyclase produces numerous cAMP molecules. PKA phosphorylates many downstream targets.
54
What are some cellular responses mediated by the epinephrine pathway?
Metabolic regulation: Activation of glycogen phosphorylase to break down glycogen. Cardiovascular effects: Increased heart rate and force of contraction.
55
What is the role of protein kinase A (PKA) in the epinephrine pathway?
PKA phosphorylates target proteins, which leads to specific cellular responses, such as metabolic changes or altered gene expression.
56
What are the major steps of the epinephrine signaling pathway?
Epinephrine binds to β-adrenergic receptor. Receptor activates G-protein by exchanging GDP for GTP. G-protein activates adenylyl cyclase. Adenylyl cyclase converts ATP to cAMP. cAMP activates protein kinase A (PKA). PKA phosphorylates targets, leading to responses.
57
What are the two main states of a G protein?
The two main states of a G protein are the active state and the inactive state. In the active state, the G protein is bound to a molecule called GTP (guanosine triphosphate). In the inactive state, the G protein is bound to a molecule called GDP (guanosine diphosphate).
58
How do G proteins switch between their active and inactive states?
The switching mechanism is shown in the image. When a G protein is activated by a signal, it binds to GTP. This causes a conformational change in the G protein, which exposes a binding site for another protein called an effector. The effector then activates the G protein, which leads to a cellular response. Once the G protein has been activated, it can hydrolyze GTP to GDP. This causes the G protein to return to its inactive state.
59
What are G proteins important for?
G proteins are important for many cellular processes, including signal transduction, cell growth, and differentiation. They are also involved in many diseases, including cancer, diabetes, and heart disease.
60
What is the inactive state of a G protein?
In the inactive state, the G protein is bound to GDP (guanosine diphosphate). This state cannot transmit signals downstream.
61
What is the role of GEF (Guanosine Nucleotide Exchange Factor)?
GEF facilitates the exchange of GDP for GTP on the G protein, activating it by enabling GTP binding.
62
What happens to the G protein when it binds to GTP?
The G protein undergoes a conformational change and becomes active, allowing it to interact with downstream effectors in signaling pathways.
63
What is the role of GAP (GTPase-activating protein)?
GAP accelerates the hydrolysis of GTP back to GDP, converting the active G protein into its inactive state and terminating the signal.
64
Why is G protein regulation important in biomedical contexts?
G protein signaling is crucial for processes like cell growth, differentiation, and communication. Dysregulation is linked to diseases such as cancer and metabolic disorders.
65
How can G protein signaling be targeted therapeutically?
Targeting GEFs or GAPs can modulate G protein signaling to treat conditions associated with dysregulation, such as cancer and genetic disorders.
66
What triggers the regulation of glycogen breakdown?
Epinephrine binds to the beta-adrenergic receptor (a GPCR) on the cell membrane, initiating the signaling cascade.
67
What happens when epinephrine binds to the beta-adrenergic receptor?
The receptor undergoes a conformational change, triggering the exchange of GDP for GTP on the G protein alpha subunit (Gsα), activating it.
68
What is the role of the activated G protein alpha subunit (Gsα)?
The activated Gsα subunit dissociates from the beta and gamma subunits and activates adenylyl cyclase.
69
What does adenylyl cyclase do?
Adenylyl cyclase catalyzes the conversion of ATP to cyclic AMP (cAMP), a secondary messenger that amplifies the signal inside the cell.
70
What is the role of cAMP in this pathway?
cAMP binds to and activates protein kinase A (PKA), which phosphorylates downstream enzymes to regulate glycogen breakdown.
71
What is the role of PKA (protein kinase A) in glycogen breakdown?
PKA phosphorylates regulatory enzymes, such as phosphorylase kinase, which activates glycogen phosphorylase to break down glycogen into glucose.
72
How is the signaling pathway terminated?
cAMP is degraded by phosphodiesterase enzymes into AMP, deactivating PKA and terminating the signaling cascade.
73
How does caffeine influence this pathway?
Caffeine inhibits phosphodiesterase, preventing the degradation of cAMP. This prolongs cAMP and PKA activity, enhancing glycogen breakdown and energy production.
74
Why is glycogen breakdown important in the fight-or-flight response?
Glycogen breakdown provides a rapid supply of glucose for energy to meet the body’s increased demands during stress or danger.
75
What diseases are associated with dysregulation of this pathway?
Dysregulation can lead to metabolic diseases like diabetes. Drugs targeting this pathway are used to treat conditions such as asthma, heart failure, and hypertension.
76
What is the structure of inactive PKA?
Inactive PKA is a holoenzyme composed of two regulatory (R) subunits and two catalytic (C) subunits. The regulatory subunits inhibit the catalytic subunits by blocking their substrate-binding cleft.
77
How is PKA activated?
PKA is activated when cAMP binds to the regulatory subunits. Each regulatory subunit binds two molecules of cAMP (four total), causing a conformational change and releasing the catalytic subunits.
78
What happens to the catalytic subunits after cAMP binds?
The catalytic subunits are released from the regulatory subunits, becoming active and capable of phosphorylating target proteins.
79
What residues do PKA phosphorylate on target proteins?
PKA phosphorylates specific serine (Ser) or threonine (Thr) residues on target proteins.
80
What is the consensus recognition site for PKA phosphorylation?
The consensus recognition site is xR[RK]x[ST]B, where x is any amino acid, [RK] is arginine or lysine, [ST] is serine or threonine, and B is a hydrophobic residue.
81
What is the role of AKAP in PKA regulation?
AKAP (A Kinase Anchoring Protein) localizes PKA to specific sites in the cell, ensuring spatial regulation and targeting specific substrates.
82
What is the role of PKA in cellular processes?
PKA regulates processes such as metabolism, gene expression, and cell signaling, including pathways like glycogen breakdown.
83
Which hormones activate the cAMP-PKA signaling pathway?
Hormones like epinephrine and glucagon activate the pathway by stimulating cAMP production through adenylyl cyclase.
84
What diseases are linked to PKA dysregulation?
Abnormal PKA activity can lead to diseases such as cancer, diabetes, and cardiac disorders.