Reading- Signal Transduction
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What is the primary role of insulin in metabolism
To promote anabolic processes and lower blood glucose levels
How does insulin signaling generally modify enzymes
By activating protein phosphatases that dephosphorylate target enzymes
What is the effect of insulin on glycogen synthase
Insulin promotes dephosphorylation and activation of glycogen synthase to increase glycogen synthesis
How does insulin affect glycogen phosphorylase
Insulin causes dephosphorylation and inactivation of glycogen phosphorylase to reduce glycogen breakdown
Which enzyme phosphorylates target proteins in glucagon signaling
Protein kinase A (PKA)
How does glucagon signaling modify enzymes
By activating PKA which phosphorylates enzymes to alter their activity
What is the effect of glucagon on phosphorylase kinase
Glucagon via PKA phosphorylates and activates phosphorylase kinase to promote glycogen breakdown
How does glucagon affect glycogen synthase
It phosphorylates and inhibits glycogen synthase to decrease glycogen synthesis
What effect does insulin have on phosphofructokinase-2 (PFK-2)
Insulin stimulates PFK-2 activity increasing fructose-2
How does glucagon alter PFK-2/FBPase-2 bifunctional enzyme activity
Glucagon causes phosphorylation that activates FBPase-2 and inhibits PFK-2 reducing fructose-2
How do insulin and glucagon coordinate to maintain blood glucose
Insulin promotes glucose uptake and storage while glucagon promotes glucose production and release
What is the role of covalent modification in insulin and glucagon signaling
It provides rapid reversible regulation of enzyme activity to adapt metabolism to nutrient status
Why is phosphorylation an effective regulatory mechanism
Because it quickly changes enzyme conformation and activity in response to signals
How does insulin signaling affect lipogenesis
Insulin activates enzymes for fatty acid synthesis by dephosphorylation and increases glucose uptake
What is the metabolic consequence of glucagon signaling during fasting
Increased gluconeogenesis
What is the primary role of metabolism regulation in cells
To ensure energy production and synthesis of end products match cellular needs.
How do individual cells coordinate their metabolic activities with other tissues
Through a sophisticated communication system involving hormones
What are the main types of regulatory signals in metabolism
Intracellular signals and intercellular signals.
What are examples of intracellular signals
Substrate availability
Why are intracellular metabolic signals typically fast
Because they respond to immediate cellular conditions.
What is the main route of metabolic communication between cells
Bloodborne hormones and neurotransmitters.
What are second messengers
Molecules that relay signals from receptors to target molecules inside the cell.
What are two major second messenger systems
The calcium/phosphatidylinositol system and the adenylyl cyclase system.
What does adenylyl cyclase do
Converts ATP to cyclic AMP (cAMP).
What activates or inhibits adenylyl cyclase
Hormones or neurotransmitters binding to G protein-coupled receptors (GPCRs).
What are the components of a G protein
Alpha (α)
How is a G protein activated
Ligand binding causes the receptor to exchange GDP for GTP on the α-subunit.
What happens after GTP binds to the G protein α-subunit
It dissociates and activates adenylyl cyclase.
What does cAMP activate
Protein kinase A (PKA).
How does cAMP activate PKA
It binds to the regulatory subunits of PKA
What do protein kinases do
Phosphorylate target proteins on serine or threonine residues.
What reverses phosphorylation of proteins
Protein phosphatases.
How is cAMP deactivated
It is hydrolyzed to 5'-AMP by cAMP phosphodiesterase.
Why are the effects of cAMP short-lived
Because phosphodiesterases rapidly break down cAMP and phosphatases remove phosphate groups.
How do cholera and whooping cough affect G proteins
They modify G proteins through ADP-ribosylation
What type of G protein activates adenylyl cyclase
Gs.
What type of G protein inhibits adenylyl cyclase
Gi.
What is the role of protein kinase A in gene regulation
It phosphorylates transcription factors that influence gene expression.
What is the role of GPCRs in signal transduction
They detect extracellular ligands and activate intracellular signaling cascades through G proteins.
What structural feature defines GPCRs
Seven transmembrane helices.
What is the main metabolic role of insulin
To signal the fed state and promote storage of nutrients.
What is the main metabolic role of glucagon
To signal the fasting state and promote the release of stored energy.
What type of receptor does insulin bind to
A receptor tyrosine kinase.
What type of receptor does glucagon bind to
A G protein-coupled receptor (GPCR).
What second messenger is activated by glucagon signaling
Cyclic AMP (cAMP).
What second messenger is activated by insulin signaling
Phosphatidylinositol-3
What enzyme is activated by cAMP in glucagon signaling
Protein kinase A (PKA).
What enzyme is activated by insulin through PIP3 signaling
Protein kinase B (PKB or Akt).
How does glucagon regulate metabolic enzymes
Through phosphorylation by PKA.
How does insulin regulate metabolic enzymes
Through dephosphorylation via activation of protein phosphatase-1.
Which hormone activates glycogen synthase
Insulin.
Which hormone inactivates glycogen synthase
Glucagon.
Which hormone activates glycogen phosphorylase
Glucagon.
Which hormone inactivates glycogen phosphorylase
Insulin.
How does PKA activate glycogen phosphorylase
By phosphorylating and activating phosphorylase kinase.
What does phosphorylase kinase do
Phosphorylates and activates glycogen phosphorylase.
How does insulin inactivate glycogen phosphorylase
By activating protein phosphatase-1 to remove phosphate groups.
What effect does insulin have on gluconeogenesis
It inhibits gluconeogenesis.
What effect does glucagon have on gluconeogenesis
It stimulates gluconeogenesis.
What effect does insulin have on glycolysis in the liver
It activates glycolysis.
What effect does glucagon have on glycolysis in the liver
It inhibits glycolysis.
What effect does insulin have on lipogenesis
It stimulates lipogenesis.
What effect does glucagon have on lipogenesis
It inhibits lipogenesis.
What effect does insulin have on ketogenesis
It inhibits ketogenesis.
What effect does glucagon have on ketogenesis
It stimulates ketogenesis.
How does insulin promote glucose uptake in muscle and fat
By increasing GLUT4 translocation to the plasma membrane.
What tissues are most responsive to insulin
Liver
What tissues are most responsive to glucagon
Primarily the liver.
What happens to protein kinase A during glucagon signaling
It becomes active and phosphorylates metabolic enzymes.
What happens to protein phosphatase-1 during insulin signaling
It becomes active and removes phosphates from metabolic enzymes.
What is the net effect of insulin on blood glucose
It lowers blood glucose.
What is the net effect of glucagon on blood glucose
It raises blood glucose.
What major metabolic processes are activated in the fed state
Glycolysis glycogenesis and lipogenesis.
What major metabolic processes are activated in the fasting state
Glycogenolysis gluconeogenesis lipolysis and ketogenesis.
How does insulin promote glucose storage in the liver
By activating glycogen synthase and promoting dephosphorylation of key enzymes.
How does glucagon promote glucose release in the liver
By activating glycogen phosphorylase and stimulating gluconeogenic enzymes.
Why doesn't glucagon affect skeletal muscle
Because skeletal muscle lacks glucagon receptors.
How does muscle respond to insulin
By increasing glucose uptake and promoting glycogen synthesis.
Why is it advantageous that glucagon does not act on muscle
It preserves muscle glycogen for immediate local use during contraction not for maintaining blood glucose.
What key enzyme in gluconeogenesis is transcriptionally upregulated by glucagon
Phosphoenolpyruvate carboxykinase.
What are the two key enzymes of glycolysis that insulin activates in the liver
Phosphofructokinase-1 and pyruvate kinase.
What enzymes are phosphorylated and inhibited by PKA during fasting
Pyruvate kinase and glycogen synthase.
How does insulin suppress ketogenesis
By increasing malonyl-CoA levels which inhibit CPT1 and block fatty acid entry into mitochondria.
How does glucagon promote ketogenesis
By activating hormone-sensitive lipase increasing fatty acid oxidation and acetyl-CoA accumulation.
What is the role of AMPK during fasting or energy stress
It mimics glucagon by promoting catabolic pathways and inhibiting anabolic ones.
What is the hormonal signal for switching from fed to fasting state
The drop in insulin and rise in glucagon.
What is the significance of the insulin to glucagon ratio
It determines whether the liver stores or mobilizes energy.
What happens to the insulin to glucagon ratio after a meal
It increases sharply favoring storage.
What happens to the insulin to glucagon ratio during an overnight fast
It decreases promoting hepatic glucose output.
Why is the liver considered a metabolic buffer
Because it responds to hormone signals to either take up or release glucose.
How does insulin regulate acetyl-CoA carboxylase
By dephosphorylating and activating it to promote fatty acid synthesis.
How does glucagon regulate acetyl-CoA carboxylase
By phosphorylating and inactivating it to inhibit lipogenesis.
What is the effect of insulin on hormone-sensitive lipase
It inhibits HSL to prevent lipolysis in adipose tissue.
What is the effect of glucagon on hormone-sensitive lipase
It activates HSL to release fatty acids from adipose tissue.
Why does gluconeogenesis require energy input
Because it synthesizes glucose from smaller precursors which is energetically costly.
What substrate does adipose tissue provide to the liver during fasting
Glycerol from lipolysis.
How does fasting increase ketone body production
By increasing beta-oxidation of fatty acids in the liver leading to acetyl-CoA accumulation.
How are ketone bodies beneficial during prolonged fasting
They spare glucose by providing an alternative energy source for the brain and muscles.
Why does insulin inhibit protein catabolism
Because it promotes protein synthesis and reduces the need to break down muscle for gluconeogenesis.
Why does glucagon increase amino acid uptake in the liver
To provide carbon skeletons for gluconeogenesis.