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BB2730 Metabolic Regulation > Receptor Tyrosine Kinases and Insulin > Flashcards

Receptor Tyrosine Kinases and Insulin Flashcards

1
Q

What is the first form of insulin synthezised in the body?

A

Pre pro-insulin

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2
Q

What are the components of pre-pro-insulin?

A

A signal sequence, A chain , B chain and C peptide

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3
Q

What is the molecular weight of insulin?

A

Approximately 6000 Daltons

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4
Q

What happens to pro-pro-insulin in the endoplasmic reticulum?

A

The signal sequnce is cleaved to form proinsulin

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5
Q

What stabilizes the structure of proinsulin?

A

Disulfide bonds(S-S bonds) betwen the A and B chains.

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6
Q

What happens to proinsulin in the Golgi apparatus?

A

The C peptide is cleaved,forming mature insulin.

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7
Q

What are the components of mature insulin?

A

A chain( 21 amino acids)
B chain(30 amino acids),connected by disulfide bonds.

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8
Q

Why is the 3D structure of insuli important?

A

It is essential for binding to the insulin receptor and ensuring biological activity.

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9
Q

Where does the conversion of pre-pro-insulin to proinsulin occur?

A

In the endoplasmic reticulum

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10
Q

Where does the conversion of proinsulin to mature insulin occur?

A

In the Golgi Apparatus

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11
Q

What are the Islets of Langerhans?

A

Clusters of endocrine cells in the pancreas that regulate glucose homeostasis

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12
Q

Approximately how many islets of Langerhans are in the pancreas?

A

Around 1 million islets, constituting 1-1.5% of pancreatic tissue

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13
Q

What is the primary function of the islets of Langerhans?

A

To regulate blood glucose levels by secretin hormons like insulin,glucagon and somatostatin.

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14
Q

What are the main cell types in the Islets of Langerhans?

A

Beta cells
Alpha cells
Delta cells

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15
Q

What hormone is secreted by beta cells,and what is its function?

A

Hormone : Insulin
Function:Lowers blood glucose by promoting glucose uptake in tissues

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16
Q

What proportion of the Islet cells are beta cells?

A

About 60%

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17
Q

What hormone is secreted by alpha cells, and what is its function?

A

Hormone : Glucagon
Function: Raises blood glucose by stimulating glycogen breakdown and gluconeogenesis in the liver

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18
Q

What portion of the islet cells are alpha cells?

A

Approximately 20%

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19
Q

What hormone is secreted by delta cells and what is its function?

A

Hormone: Somatostatin
Function: Regulates and inhibits the secretion of insulin and glucagon it also controls gastrointestinal processes

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20
Q

What proportion of the Islet cells are delts cells?

A

About 10%

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21
Q

What do the red,green and blue signals represent in the immunofluorescence image of the islets?

A

Red:Insulin-producing B-cells.
Green:Glucagon-producing a-cells.
Blue:Nuclear staining (all cells)

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22
Q

What seperates the endocrine islet cells from the exocrine pancreas tissue?

A

A distinct boundary visisble under microscopic and immunofluorescent imaging

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23
Q

What is the role of somatostatin in the pancreas?

A

To fine-tune hormone secretion by inhibiting insulin and glucagon release.

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24
Q

where are the islets of Langerhands located within the pancreas?

A

Scattered throughout the pancreatic tissue, surrounded by exocrine cells.

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25
What transporter is repsondsible for glucose entry into pacreatic B cells?
The GLUT2 transporter
26
What enzyme phosphorylates glucose inside B-cells?
Glucokinase
27
What happens to glucose after it is phosphorylated in b-cells?
It enters glycolysis and oxidative phosphorylation,generating ATP.
28
How does an increase in ATP/ADP affect ratio ATP-sensitive potassium channels
ATP binds to these channels, causing them to close.
29
What is the effect of closing ATP-sensitive K⁺ channels?
It causes membrane depolarization by preventing K⁺ efflux.
30
What channels open as a result of membrane depolarization?
Voltage-gated calcium (Ca²⁺) channels.
31
What is the role of calcium ions (Ca²⁺) in insulin secretion?
Calcium influx triggers insulin-containing storage granules to fuse with the membrane, leading to exocytosis of insulin.
32
What is the final step in insulin secretion?
Insulin is released into the bloodstream via exocytosis.
33
What process links glucose metabolism to insulin secretion in β-cells?
The rise in the ATP/ADP ratio, which closes K⁺ channels, depolarizes the membrane, and opens Ca²⁺ channels.
34
What is the clinical relevance of insulin secretion?
Dysfunctions in this process can lead to conditions such as diabetes mellitus.
35
What triggers the fusion of insulin storage granules with the cell membrane?
The influx of calcium ions (Ca²⁺) into the β-cell.
36
What role does GLUT2 play in insulin secretion?
GLUT2 allows glucose uptake into β-cells, initiating the secretion process.
37
38
39
What happens to the ATP-sensitive K⁺ channel under low glucose conditions?
It remains open, allowing K⁺ efflux and maintaining the resting membrane potential.
40
What is the relationship between depolarization and calcium influx in β-cells?
Depolarization causes the opening of voltage-gated Ca²⁺ channels, allowing calcium influx.
41
What are receptor tyrosine kinases (RTKs)?
RTKs are cell surface receptors that act as both receptors and enzymes, playing a critical role in cell signaling for growth, differentiation, and survival.
41
What are the three main structural components of RTKs?
Extracellular ligand-binding domain Transmembrane α-helix Intracellular kinase catalytic site
41
What is the function of the extracellular domain of RTKs?
It binds specific ligands, such as growth factors (e.g., insulin, EGF).
42
What is the role of the transmembrane α-helix in RTKs?
It spans the plasma membrane and connects the extracellular domain to the intracellular kinase domain.
43
What is the function of the intracellular kinase domain in RTKs?
It phosphorylates tyrosine residues on the receptor itself or other proteins, enabling signal transduction.
44
What type of residue is phosphorylated by RTKs?
Tyrosine residues.
44
What happens when a ligand binds to an RTK?
The receptor undergoes dimerization. The kinase domain becomes active and performs autophosphorylation.
45
What is autophosphorylation in RTKs?
The process where the kinase domain phosphorylates tyrosine residues on its own cytoplasmic tail.
46
How does RTK phosphorylation propagate a signal?
Phosphorylated tyrosines act as docking sites for intracellular signaling proteins, initiating downstream pathways like MAPK or PI3K/AKT.
47
Why are RTKs important in biomedical science?
RTKs regulate critical processes like growth and metabolism. Dysregulation of RTKs is associated with diseases like cancer and diabetes.
48
What is the role of RTKs in cancer?
Overactive RTKs can lead to uncontrolled cell proliferation and tumor growth.
49
Name two key signaling pathways activated by RTKs.
The MAPK pathway and the PI3K/AKT pathway.
50
What happens when ATP binds to the kinase domain of an RTK?
The RTK phosphorylates tyrosine residues, activating downstream signaling proteins.
51
What is the structure of the insulin receptor?
The insulin receptor is a heterotetramer composed of: Two α-subunits (130 kDa, 735 amino acids). Two β-subunits (95 kDa, 620 amino acids).
52
What links the α- and β-subunits in the insulin receptor?
Disulfide (S-S) bonds.
53
Where are the α-subunits of the insulin receptor located, and what is their function?
Location: Extracellular. Function: Contain the hormone-binding domains that bind insulin.
54
What is the role of the β-subunits in the insulin receptor?
They span the membrane and extend into the cytoplasm. Contain the ATP-binding domain and tyrosine kinase domain for signaling.
55
What happens when insulin binds to its receptor?
The receptor undergoes a conformational change. The tyrosine kinase domain in the β-subunits becomes active. Autophosphorylation occurs, initiating downstream signaling.
56
What is the primary function of the insulin receptor?
To regulate glucose uptake, metabolism, and other cellular responses.
57
What type of receptor is the glucagon receptor?
A G-protein-coupled receptor (GPCR).
58
What is the structure of the glucagon receptor?
It has seven transmembrane helices and extracellular and intracellular domains.
59
What happens when glucagon binds to its receptor?
The receptor activates an associated G-protein. G-protein activation triggers downstream signaling, such as cAMP production.
60
What is the primary function of the glucagon?
To promote glucose release from the liver during fasting.
61
How does the insulin receptor signaling differ from glucagon receptor signaling?
Insulin receptor: Uses tyrosine phosphorylation for signaling. Glucagon receptor: Activates G-proteins and increases cAMP.
62
What clinical condition is associated with insulin receptor dysfunction?
Insulin resistance,a hallmark of type 2 diabetes.
63
How can dysregulation of the glucagon receptor contribute to diabetes?
Overactivation of the glucagon receptor can lead to excess glucose release,worsening hypergycemia.
64
What are the main ligands for the insulin and glucagon receptors?
Insulin receptor: Insulin. Glucagon receptor: Glucagon.
65
What is the B adrenergic receptor?
It is a G protein couples receptor that responds to catecholamins like adrenaline and nonadrrenaline
66
How many transmembrane helices does the β-adrenergic receptor have?
It has seven transmembrane helices.
67
What is the function of the extracellular side of the β-adrenergic receptor?
It contains the ligand-binding site, where molecules like adrenaline bind.
68
What happens when a ligand binds to the β-adrenergic receptor?
The receptor undergoes a conformational change and activates intracellular G-proteins.
69
Which G-protein is associated with the B adrenergic receptor?
The receptor activates Gs protein(stimulatory G-proteins).
70
Which G-protein is associated with B adregenergic recepto>
The receptor activates Gs proteins(stimulating G-proteins).
71
What signalling molecule is produced when Gs proteins are acivate?
Cyclic AMP (cAMP) is produced.
72
What is the role of cAMP in β-adrenergic receptor signaling?
cAMP activates protein kinase A (PKA), which phosphorylates target proteins to elicit physiological responses.
73
What are the physiological effects of β-adrenergic receptor activation in the heart?
Increases heart rate and contractility (β1 receptor subtype).
74
What is the physiological effect of β-adrenergic receptor activation in the lungs?
Causes bronchodilation (β2 receptor subtype).

BB2730 Metabolic Regulation (5 decks)

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