chapter 12 pt 3 Messengers, Calcium, Signal Termination, RTKs, and Insulin

What is the difference between primary and secondary messengers?

Primary messengers act outside the cell, while secondary messengers act inside the cell.

Where do primary messengers act?

On receptors located on the cell surface.

Why do most primary messengers not enter cells?

Because they cannot cross the plasma membrane.

What are examples of primary messengers?

Epinephrine, insulin, acetylcholine, nitric oxide, hormones, and steroids.

What are secondary messengers?

Small intracellular molecules or ions that relay signals within the cell.

Where do secondary messengers function?

Inside the cell.

What are examples of secondary messengers?

cAMP, calcium ions, DAG, and IP3.

What are key characteristics of secondary messengers?

They are small, non-protein, water-soluble molecules that relay intracellular signals.

Why is calcium considered an important secondary messenger?

It regulates many physiological processes and is easily detected when its concentration changes.

What physiological processes depend on calcium signaling?

Neurotransmitter release and muscle contraction.

Why does calcium bind well to proteins?

Because it can interact with oxygen-containing groups on amino acid side chains.

Which amino acid side chains commonly bind calcium?

Aspartate and glutamate.

What does IP3 do?

It promotes increased calcium ion permeability.

Why is intracellular calcium normally kept low?

To prevent precipitation and formation of insoluble calcium salts.

What is the typical intracellular calcium concentration mentioned in lecture?

Approximately 100 nM.

Why are small increases in calcium easy to detect?

Because baseline intracellular calcium levels are very low.

What is an agonist?

A molecule that activates a receptor in the same way as the natural ligand.

What is the relationship between epinephrine and isoproterenol?

Isoproterenol is an agonist of epinephrine.

What is an antagonist?

A molecule that binds a receptor and blocks activation by the natural ligand.

What is the relationship between epinephrine and propranolol?

Propranolol is an antagonist of epinephrine.

How does an antagonist inhibit signaling?

It binds strongly to the receptor and prevents the natural ligand from activating it.

What enzyme converts cAMP back into AMP?

Phosphodiesterase.

Why is signaling amplification significant in the epinephrine pathway?

A single ligand can ultimately affect thousands of molecules downstream.

What are major mechanisms of signal termination?

G protein self-inactivation, reduced ligand concentration, and cAMP hydrolysis.

How can a G protein self-inactivate?

The alpha subunit hydrolyzes GTP to GDP.

What happens when GDP replaces GTP on the alpha subunit?

The alpha subunit reassociates with beta and gamma subunits to reform the inactive G protein.

What is the function of phosphatases?

They remove phosphate groups from proteins.

How do phosphatases affect signaling pathways?

They reverse phosphorylation-dependent cellular responses.

What is desensitization of a GPCR?

A process that weakens signaling even when the ligand remains bound.

How is beta-adrenergic receptor desensitization achieved?

Through receptor phosphorylation and beta-arrestin binding.

What is beta-arrestin?

An adaptor protein that binds phosphorylated GPCRs.

What is the function of beta-arrestin?

It promotes receptor internalization and desensitization.

Where does beta-arrestin bind?

To the cytoplasmic side of the receptor.

How can a receptor be recycled after desensitization?

After endocytosis, the receptor can be dephosphorylated and returned to the plasma membrane.

What are enzyme-linked membrane receptors?

Receptors that function both as signal receivers and enzymes.

How do enzyme-linked receptors differ from GPCRs structurally?

They typically span the membrane only once.

What is the major function of receptor tyrosine kinases?

They transmit extracellular signals through kinase activity.

What cellular processes can receptor tyrosine kinases regulate?

Cell growth, cell division, and metabolism.

What is a receptor tyrosine kinase?

A membrane receptor with intrinsic kinase activity that phosphorylates tyrosine residues.

What is an important example of a receptor tyrosine kinase?

Insulin receptor.

What is the structure of the insulin receptor?

Two extracellular alpha subunits and two transmembrane beta subunits linked by disulfide bonds.

Which part of the insulin receptor binds insulin?

The extracellular alpha subunits.

Which part of the insulin receptor contains kinase activity?

The beta subunits.

What is the activation loop of the insulin receptor?

A region containing tyrosine residues whose phosphorylation activates the receptor.

What happens when insulin binds its receptor?

It activates the receptor's kinase activity.

What protein is activated downstream of insulin signaling?

Protein kinase B.

What is GLUT4?

A glucose transporter found in intracellular storage vesicles.

How does insulin affect GLUT4?

It promotes movement of GLUT4-containing vesicles to the plasma membrane.

What is the result of GLUT4 insertion into the membrane?

Increased glucose uptake by cells.

How does glucose move through GLUT4?

By facilitated diffusion down its concentration gradient.

Does GLUT4-mediated glucose transport require ATP?

No, it occurs by facilitated diffusion.

What happens to GLUT4 when insulin levels decrease?

GLUT4 is removed from the membrane by endocytosis.

Where is GLUT4 stored after endocytosis?

In intracellular vesicles and endosomal compartments.

Why does removing GLUT4 from the membrane reduce glucose uptake?

Fewer glucose transporters are available at the cell surface.