Biochemistry : G Protein Pathway

Study concepts, example questions & explanations for Biochemistry

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Example Questions

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Example Question #1 : Biochemical Signaling

A scientist is running an experiment to determine the effects of a new drug on cells. Aftering treating cells with the drug, the scientist observes an increase in the amount of diacylglycerol found within these cells. Based on this information, what type of receptor is this drug likely interacting with?

Possible Answers:

Intracellular receptor

G protein-coupled receptor

Ionotropic receptor

Dihydropyridine receptor

Receptor tyrosine kinase

Correct answer:

G protein-coupled receptor

Explanation:

The observed increase in diacylglycerol (DAG) is indicative of the activation of a GProtein-Coupled Receptor (GPCR).

Upon binding of a ligand to a GPCR, a conformational change in the receptor is transmitted to a G protein bound to the cell membrane within the cell. This subsequently causes the alpha-subunit of the G protein to lose its bound GDP, and in exchange it receives GTP. This, in turn, activates the G protein, causing the alpha subunit to dissociate from the beta-gamma subunit. This newly liberated alpha subunit-GTP complex then goes on to activate another component of the signal transduction cascade. There are two main types of GPCR signaling pathways, depending on the type of alpha subunit involved.

cAMP Pathway: When the alpha subunit is stimulatory, denoted as , it will activate an enzyme in the plama membrane called adenylyl cylcase. Activation of this enzyme results in the conversion of ATP into cAMP. cAMP, in turn, acts as a second messenger within the cell, activing Protein Kinase A (PKA). This protein kinase then goes on to phosphorylate several proteins within the cell, which leads to a response. Furthermore, the G protein may also be inhibitory and denoted as . This alpha subunit essentially does the opposite of what  does. That is, it acts to inhibit adenylyl cyclase, with a subsequent decrease in intracellular levels of cAMP and a reduction in the activity of PKA.

Phosphatidylinositol Pathway: In this case, the G protein is denoted as . This particular G protein goes on to activate an enzyme called phospholipase C (PLC). PLC, in turn, cleaves a certain phospholipid within the plasma membrane called phosphatidylinositol-4,5-bisphosphate () into two products, inositol-1,4,5-trisphosphate () and diacylglycerol (DAG).  dissociates from the membrane and binds to a receptor on the endoplasmic reticulum, stimulating the release of  into the cytosol. Together, DAG and  work together to activate Protein Kinase C (PKC), which then goes on to phosphorylate many proteins within the cell, leading to a cellular response.

And briefly, receptor tyrosine kinases (RTK) are receptors located in the plasma membrane. Upon binding its ligand, RTK's have two intracellular domains that phosphorylate each other, thus activating the receptor. The RTK then goes on to trigger a signal transduction cascade.

Ionotropic receptors are located in the plasma membrane, and they also serve as ion channels through which ions can flow. Generally, binding of ligand to ionotropic receptors induces a conformational change in the receptor that causes the ion channel to open.

The dihydropyridine receptor (DHP) is located in the plasma membrane and is generally associated with another receptor known as the ryanodine receptor, located in the membrane of the endoplasmic reticulum. Generally, the DHP receptor is activated by a change in membrane voltage, and upon stimulation causes: 1) an influx of  from the extracellular fluid into the cytosol, and 2) is mechanically coupled to the ryanodine receptor, stimulating it to release  from the endoplasmic reticulum into the cytoplasm.

And finally, as the name implies, intracellular receptors are not located in the plasma membrane, but instead located in either the cytosol or nucleus. For a ligand to bind this class of receptor, it must be able to diffuse across the plasma membrane to make its way into the cell. Generally, upon activation, intracellular receptor-ligand complexes act as transcription factors, directly modulating the activity of certain genes by altering their expression.

Example Question #2 : G Protein Pathway

Which subclass of G-protein coupled receptors directly signal inhibition of adenylyl cyclase?

Possible Answers:

Correct answer:

Explanation:

 signals inhibition to adenylyl cyclase, thus decreasing the amount of cAMP produced.  has the opposite stimulatory effect on adenylyl cyclase. None of the other answers directly target adenylyl cyclase.

Example Question #3 : G Protein Pathway

Which of the following is not a correct statement about G-proteins? 

Possible Answers:

The  subunit of the G-protein detaches once GDP is converted to GTP

One mechanism of G-proteins activates the phosphoinositide cascade

, and  are 3 types of G-proteins

The  subunit reattaches once the GTP gets hydrolyzed to GDP

Correct answer:

, and  are 3 types of G-proteins

Explanation:

, and  are not types of G proteins. Instead, they are types of  subunits of a G-protein. 

Example Question #2 : Biochemical Signaling

Which of the following is a possible consequence of activation of a G protein-coupled receptor?

I. Increasing cAMP levels

II. Increase the flow of sodium ions across the plasma membrane

III. Increasing protein kinase C (PKC)

Possible Answers:

III only

II and III

I and III

I only

Correct answer:

I and III

Explanation:

The G protein-coupled receptor (GPCR) is a signaling receptor found in many cells throughout the body. It utilizes a second messenger system to convey signals to the cell. This means that, upon activation, the GPCR will activate second messenger molecules such as cAMP that will cause biochemical changes inside the cell. One of the downstream molecules cAMP acts on is called protein kinase C (PKC). Recall that kinases are enzymes that facilitate the phosphorylation of molecules. PKC will phosphorylate several molecules that activate different signaling pathways.

Note that ion transport (such as sodium ion transport) occurs when an ion channel is activated. G protein-coupled receptors are not ion channels; therefore, they do not facilitate the movement of ions across membranes.

Example Question #3 : Biochemical Signaling

A researcher is analyzing the effects of a receptor on a cell. He observes that the receptor autophosphorylates itself at certain amino acid residues. What can you conclude about this receptor?

Possible Answers:

A kinase will be activated

More than one of these are correct

Aspartic acid residues are phosphorylated

It will not lead to an increase in protein kinase C levels

Correct answer:

More than one of these are correct

Explanation:

There are several types of receptors found on a cell membrane. These receptors function to transduce an external signal (in the form of a ligand or voltage changes) into an intracellular signal. The question states that the receptor autophosphorylates itself. This means that the receptor must have kinase activity. Recall that, upon activation (by ligand binding), receptor tyrosine kinases self phosphorylate their tyrosine residues; therefore, the receptor stated in this question is a receptor tyrosine kinase. After auto-phosphorylation, the receptor tyrosine kinase will phosphorylate other molecules (kinase) that will lead to a signaling cascade.

As mentioned, tyrosine residues are phosphorylated, not aspartic acid residues.

Example Question #6 : G Protein Pathway

Which of the following correctly characterizes a G protein-coupled receptor (GPCR)?

Possible Answers:

It is only found in the central nervous system

It responds to changes in voltage across the membrane

It can lead to a decrease in calcium levels in the cell

It responds to insulin

Correct answer:

It can lead to a decrease in calcium levels in the cell

Explanation:

G protein coupled-receptors can be classified into three categories: Gq, Gi, or Gs. Gq and Gs are stimulatory receptors whereas Gi is inhibitory. Gq activates the phospholipase C (PLC) pathway and Gs activates the cAMP and, subsequently, protein kinase C (PKC) pathway. Gi, on the other hand, inhibits several signaling cascades in the cells. One of the prominent effects of Gi receptor is that it inhibits the increase of calcium levels intracellularly. Recall that calcium levels are kept at a very low concentration inside the cell. Upon activation of certain pathways, calcium influx can occur from either the outside of the cell or from within the organelles (such as rough endoplasmic reticulum). This will lead to an increase in the cytoplasmic calcium levels. Increase in cytoplasmic calcium levels will initiate several pathways inside the cell. To prevent overactivity of these pathways, calcium levels are closely controlled within the cell. One way to regulate the calcium levels is by the activation of Gi receptor.

Insulin binds to receptor tyrosine kinases, G protein coupled receptors are found throughout the body (not just the central nervous system), and GPCR's respond to ligand binding, not voltage changes.

Example Question #4 : Biochemical Signaling

Which of the following statements about heterotrimeric G proteins and their receptors is incorrect?

Possible Answers:

When GTP binds to the alpha subunit of the G protein, the beta-gamma subunit dissociates from the alpha subunit.

A Cys-S linked palmitoyl group faces the extracellular region.

G protein-coupled receptors may be desensitized by serine phosphorylation.

G-protein coupled receptors contain nine transmembrane alpha helices.

Correct answer:

G-protein coupled receptors contain nine transmembrane alpha helices.

Explanation:

G protein-coupled receptors contain nine seven transmembrane alpha helices. All other statements are true of G protein-coupled receptors.

Example Question #8 : G Protein Pathway

Which of the following statements about the adenylate cyclase signaling system is incorrect?

Possible Answers:

Adenylate cyclase is involved in the initial pathway that activates protein kinase A by binding four cAMP molecules.

cAMP-phosphodiesterases limit second messenger activity.

Toxins such as cholera and pertussis can inhibit certain steps in the G protein pathway. 

Mammalian adeylate cyclases have nine different isoforms, and the structure is predicted to be six transmembrane helices.

The Gq subunit stimulates adenlyate cyclase to produce cAMP.

Correct answer:

The Gq subunit stimulates adenlyate cyclase to produce cAMP.

Explanation:

The Gq Gs-alpha bound to GTP dissociates and stimulates adenlyate cyclase to produce cAMP. (Gq is involved in the phosphoinositide pathway, not the adenylate cyclase pathway.) All other answer choices are correct with regards to the adenylate cyclase signaling system.

Example Question #9 : G Protein Pathway

Which of the following is not a second messenger produced by the phosphoinositide pathway?

Possible Answers:

cAMP

DAG (diacylglycerol)

Correct answer:

cAMP

Explanation:

cAMP is a second messenger produced by the adenylate cyclase pathway (among other pathways).

Example Question #5 : Biochemical Signaling

Glucagon and its liver receptor and epinephrine and its beta adrenergic receptor both activate __________ causing an increase in __________.

Possible Answers:

adenylate cyclase . . . cAMP

the sodium-potassium pump . . . membrane potential

phospholipase C . . . protein kinase c

voltage gated  channels . . . muscle contraction

Correct answer:

adenylate cyclase . . . cAMP

Explanation:

These are examples of heterotrimeric G protein-dependent signaling. Glucagon and epinephrine hormones both cause GTP to bind to adenylate cyclase, which produces the second messenger cAMP.

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