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BB2730 Metabolic Regulation > G-Protein coupled receptors and regulation of glycogenolysis > Flashcards

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
Q

Give an example of endocrine signaling in the body.

A

Blood glucose regulation by insulin from the pancreas.

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26
Q

What is glycogenolysis?

A

Glycogenolysis is the process by which glycogen, a stored form of glucose, is broken down into glucose for energy use.

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26
Q

What is epinephrine?

A

Epinephrine is a hormone that is released in response to stress, such as exercise or fear.

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26
Q

What is glycogen phosphorylase?

A

Glycogen phosphorylase is the enzyme that breaks down glycogen into glucose-1-phosphate.

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26
Q

What is phosphorylase kinase?

A

Phosphorylase kinase is an enzyme that phosphorylates and activates glycogen phosphorylase.

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27
Q

How is glycogen phosphorylase regulated?

A

Glycogen phosphorylase is regulated by calcium ions (Ca2+). When Ca2+ levels are high, glycogen phosphorylase is more active.

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27
Q

What is the epinephrine-mediated mechanism of glycogenolysis?

A

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.

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28
Q

What are G protein-coupled receptors(GPCRs)?

A

GPCRs are a large family of cell surface receptors that play a key role in signal transduction by tranmitting extracellular signals into the cell.

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29
Q

How many transmembrane domains do GPCRs have, and what are they made of?

A

GPCRs have 7 transmembrane a-helicases made of 22-24 hydrophobic amino acids, anchoring them in the cell membrane

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30
Q

What is the role of the extracellular regions of GPCRs?

A

The extracellular regions are involved in ligand( signal molecule) binding.

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31
Q

What is the role of the intracellular loops of GPCRs?

A

Intracellular loops facilitate intraction with G-proteins, specifically the loops between TM5/TM6 and TM3/TM4.

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32
Q

What are the N-terminus and C-terminus of GPCRs?

A

The N-termimus is located extracellularly,and the C-termminus is located intracellularly.

33
Q

What happens when a ligand binds to a GPCR?

A

Ligand binding causes a conformational change in the receptor, activating its associated G-protein

34
Q

What are the components of the heterotrimeric G-protein complex?

A

The G-protein complex has three subunits: Gα, Gβ, and Gγ.

35
Q

What happens to the G-protein in its inactive state?

A

In the inactive state, the Gα subunit is bound to GDP (guanosine diphosphate).

36
Q

How is the G-protein activated?

A

Upon ligand binding, the Gα subunit exchanges GDP for GTP, causing it to dissociate from the Gβγ dimer.

37
Q

What happens after the G-protein is activated?

A

The Gα subunit and the Gβγ dimer activate downstream signaling pathways, leading to cellular responses such as enzyme activation or ion channel modulation.

38
Q

What is an example of a GPCR, and what does it regulate?

A

The β-adrenergic receptor is a GPCR that binds epinephrine and regulates functions like heart rate and energy mobilization.

39
Q

What does GDP-to-GTP exchange in G-proteins signify?

A

It signifies G-protein activation, which triggers intracellular signaling cascades.

40
Q

What do G proteins bind to regulate their activity?

A

G proteins bind GTP (guanosine triphosphate) and GDP (guanosine diphosphate) to regulate their activity.

41
Q

What is the structure of G proteins?

A

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
Q

To which protein superfamily do G proteins belong?

A

G proteins belong to the GTPase superfamily, which hydrolyzes GTP to GDP.

43
Q

What is the active state of a G protein?

A

The active state occurs when the α subunit binds GTP, allowing the α subunit and βγ dimer to interact with downstream effectors.

44
Q

What is the inactive state of a G protein?

A

The inactive state occurs when the α subunit binds GDP, and the three subunits remain tightly associated.

45
Q

What role do G proteins play in signal transduction?

A

G proteins act as molecular switches, relaying signals from GPCRs to downstream targets like enzymes (e.g., adenylate cyclase) and ion channels.

46
Q

What physiological processes do G proteins regulate?

A

G proteins regulate processes such as metabolism, growth, and sensory perception.

47
Q

What is the general sequence of events in signal transduction?

A

Signal (ligand binding).
Reception (ligand-receptor interaction).
Amplification (signal strength increases).
Transduction (intracellular signaling cascade).
Response(s) (cellular changes).

48
Q

What role does epinephrine play in signaling?

A

Epinephrine acts as a ligand (first messenger) that binds to the β-adrenergic receptor, triggering a cascade of intracellular signaling events.

49
Q

What happens when epinephrine binds to the β-adrenergic receptor?

A

The receptor undergoes a conformational change, becoming activated and initiating downstream signaling via G-proteins.

50
Q

What is the role of G-proteins in the epinephrine pathway?

A

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
Q

What is the function of adenylyl cyclase in this pathway?

A

Adenylyl cyclase converts ATP to cAMP, which acts as a second messenger to amplify the signal.

52
Q

How does cAMP contribute to the signaling cascade?

A

cAMP activates protein kinase A (PKA), which phosphorylates target proteins, leading to various cellular responses.

53
Q

How is the epinephrine pathway an example of signal amplification?

A

One epinephrine molecule activates multiple receptors.
Each receptor activates many G-proteins.
Adenylyl cyclase produces numerous cAMP molecules.
PKA phosphorylates many downstream targets.

54
Q

What are some cellular responses mediated by the epinephrine pathway?

A

Metabolic regulation: Activation of glycogen phosphorylase to break down glycogen.
Cardiovascular effects: Increased heart rate and force of contraction.

55
Q

What is the role of protein kinase A (PKA) in the epinephrine pathway?

A

PKA phosphorylates target proteins, which leads to specific cellular responses, such as metabolic changes or altered gene expression.

56
Q

What are the major steps of the epinephrine signaling pathway?

A

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
Q

What are the two main states of a G protein?

A

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
Q

How do G proteins switch between their active and inactive states?

A

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
Q

What are G proteins important for?

A

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
Q

What is the inactive state of a G protein?

A

In the inactive state, the G protein is bound to GDP (guanosine diphosphate). This state cannot transmit signals downstream.

61
Q

What is the role of GEF (Guanosine Nucleotide Exchange Factor)?

A

GEF facilitates the exchange of GDP for GTP on the G protein, activating it by enabling GTP binding.

62
Q

What happens to the G protein when it binds to GTP?

A

The G protein undergoes a conformational change and becomes active, allowing it to interact with downstream effectors in signaling pathways.

63
Q

What is the role of GAP (GTPase-activating protein)?

A

GAP accelerates the hydrolysis of GTP back to GDP, converting the active G protein into its inactive state and terminating the signal.

64
Q

Why is G protein regulation important in biomedical contexts?

A

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
Q

How can G protein signaling be targeted therapeutically?

A

Targeting GEFs or GAPs can modulate G protein signaling to treat conditions associated with dysregulation, such as cancer and genetic disorders.

66
Q

What triggers the regulation of glycogen breakdown?

A

Epinephrine binds to the beta-adrenergic receptor (a GPCR) on the cell membrane, initiating the signaling cascade.

67
Q

What happens when epinephrine binds to the beta-adrenergic receptor?

A

The receptor undergoes a conformational change, triggering the exchange of GDP for GTP on the G protein alpha subunit (Gsα), activating it.

68
Q

What is the role of the activated G protein alpha subunit (Gsα)?

A

The activated Gsα subunit dissociates from the beta and gamma subunits and activates adenylyl cyclase.

69
Q

What does adenylyl cyclase do?

A

Adenylyl cyclase catalyzes the conversion of ATP to cyclic AMP (cAMP), a secondary messenger that amplifies the signal inside the cell.

70
Q

What is the role of cAMP in this pathway?

A

cAMP binds to and activates protein kinase A (PKA), which phosphorylates downstream enzymes to regulate glycogen breakdown.

71
Q

What is the role of PKA (protein kinase A) in glycogen breakdown?

A

PKA phosphorylates regulatory enzymes, such as phosphorylase kinase, which activates glycogen phosphorylase to break down glycogen into glucose.

72
Q

How is the signaling pathway terminated?

A

cAMP is degraded by phosphodiesterase enzymes into AMP, deactivating PKA and terminating the signaling cascade.

73
Q

How does caffeine influence this pathway?

A

Caffeine inhibits phosphodiesterase, preventing the degradation of cAMP. This prolongs cAMP and PKA activity, enhancing glycogen breakdown and energy production.

74
Q

Why is glycogen breakdown important in the fight-or-flight response?

A

Glycogen breakdown provides a rapid supply of glucose for energy to meet the body’s increased demands during stress or danger.

75
Q

What diseases are associated with dysregulation of this pathway?

A

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
Q

What is the structure of inactive PKA?

A

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
Q

How is PKA activated?

A

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
Q

What happens to the catalytic subunits after cAMP binds?

A

The catalytic subunits are released from the regulatory subunits, becoming active and capable of phosphorylating target proteins.

79
Q

What residues do PKA phosphorylate on target proteins?

A

PKA phosphorylates specific serine (Ser) or threonine (Thr) residues on target proteins.

80
Q

What is the consensus recognition site for PKA phosphorylation?

A

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
Q

What is the role of AKAP in PKA regulation?

A

AKAP (A Kinase Anchoring Protein) localizes PKA to specific sites in the cell, ensuring spatial regulation and targeting specific substrates.

82
Q

What is the role of PKA in cellular processes?

A

PKA regulates processes such as metabolism, gene expression, and cell signaling, including pathways like glycogen breakdown.

83
Q

Which hormones activate the cAMP-PKA signaling pathway?

A

Hormones like epinephrine and glucagon activate the pathway by stimulating cAMP production through adenylyl cyclase.

84
Q

What diseases are linked to PKA dysregulation?

A

Abnormal PKA activity can lead to diseases such as cancer, diabetes, and cardiac disorders.

BB2730 Metabolic Regulation (4 decks)

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