Category 5 Flashcards
(19 cards)
Describe the steps involved in GPCR activation and G protein interaction.
- The extracellular portion of a GPCR binds a signalling molecule.
- This increases the affinity of the G protein’s α subunit for GTP, causing it to exchange GDP for GTP.
- The α subunit then dissociates from the βγ complex.
How does adrenaline influence glucose homeostasis, and what are its target tissues?
Adrenaline enhances glucose availability during stress by stimulating glycogen breakdown in the liver and muscle, and lipolysis in adipose tissue. Its main target tissues include the liver, muscle, and adipose tissue.
Describe the roles of glucagon and insulin in regulating glycogen metabolism in the liver.
Glucagon promotes glycogen breakdown (glycogenolysis) and inhibits glycogen synthesis, while insulin does the opposite by stimulating glycogen synthesis and inhibiting breakdown.
Outline the steps involved in the processing and secretion of insulin from pancreatic β-cells.
- Synthesised as preproinsulin.
- Processed in the ER to proinsulin.
- Cleaved in the Golgi into insulin and C-peptide.
- Packaged into granules and secreted via exocytosis in response to high blood glucose.
How is cAMP inactivated, and why is this important?
cAMP is inactivated by phosphodiesterase, which converts it to AMP. This inactivation is important because it allows for the rapid termination of the signal and prevents overstimulation.
Explain the function of GLUT4 transporters and how insulin regulates their activity.
GLUT4 found in muscle and adipose tissue.
Insulin triggers the movement of GLUT4 from intracellular stores to the plasma membrane, enhancing glucose uptake; in the absence of insulin, GLUT4 remains intracellular.
Describe how adrenaline initiates a signalling cascade in skeletal muscle.
Adrenaline binds to a GPCR, which activates a G protein, which in turn activates adenylyl cyclase. Adenylyl cyclase increases cAMP levels, which activates protein kinase A (PKA). PKA phosphorylates and activates phosphorylase kinase, which activates glycogen phosphorylase, leading to glycogen breakdown.
What are the three main types of cell surface receptors?
ion-channel-coupled receptors,
enzyme-coupled receptors,
GPCRs.
What is the mechanism behind cholera toxin’s effect on intestinal epithelial cells?
Cholera toxin modifies Gs proteins in intestinal epithelial cells such that GTP is never hydrolysed to GDP. This results in continuous activation of adenylyl cyclase, leading to increased cAMP levels and excessive chloride and water secretion into the gut, causing diarrhea.
Describe the role of ATP-gated K⁺ channels in insulin secretion from pancreatic β cells.
Increased glucose metabolism raises intracellular ATP, which closes ATP-sensitive K⁺ channels, depolarizing the cell membrane. This opens voltage-gated Ca²⁺ channels, allowing calcium influx and triggering insulin exocytosis.
What are the main cell types found in the endocrine pancreas (Islets of Langerhans), and what hormones do they secrete?
The endocrine pancreas contains α-cells (secrete glucagon), β-cells (secrete insulin), and δ-cells (secrete somatostatin). Together, these cells regulate blood glucose levels.
How do ion-channel-coupled receptors work, and where are they primarily found?
Ion-channel-coupled receptors open in response to the binding of an extracellular signal molecule, allowing ions to flow across the plasma membrane. This results in an electrical current. They are primarily found at neuronal synapses and are important for electrically excitable nerve and muscle cells.
What is adenylyl cyclase and what second messenger does it produce?
Adenylyl cyclase is an enzyme that is often a target of G proteins. It catalyses the formation of the second messenger cyclic AMP (cAMP) from ATP.
Explain how insulin binding to its receptor leads to the activation of downstream signaling pathways and the uptake of glucose by cells.
Insulin binds to its receptor, activating its tyrosine kinase activity and phosphorylating IRS-1. This initiates the PI3K-Akt pathway, which promotes translocation of GLUT4 transporters to the membrane, increasing glucose uptake.
Describe how corticosteroids like cortisol exert their effects on target cells, including their mechanism of action.
Cortisol binds to intracellular receptors, forming a hormone-receptor complex that enters the nucleus and acts as a transcription factor. This alters gene expression, leading to slower but sustained cellular effects.
Explain the basic mechanism of enzyme-coupled receptors.
Enzyme-coupled receptors either have intrinsic enzyme activity or associate with an enzyme upon activation. The activated enzyme can then start a signalling cascade, often through autophosphorylation of tyrosine residues.
List four hormones involved in glucose homeostasis and indicate their chemical class.
Insulin (peptide), Glucagon (peptide), Adrenaline (amine), and Cortisol (steroid). These hormones are secreted by the pancreas (insulin and glucagon), adrenal medulla (adrenaline), and adrenal cortex (cortisol).
What happens after the α subunit and βγ complex dissociate from the G protein?
Both the α subunit and the βγ complex can then independently activate target proteins in the plasma membrane, such as enzymes or ion channels. The activated target initiates a downstream signalling cascade.
What is the role of a G protein in GPCR signalling?
A G protein is a trimeric GTP-binding protein that binds to and is activated by an activated GPCR. It then activates an enzyme or ion channel, initiating a signalling cascade.
