Biochemical Signaling - Biochemistry

Tryptophan hydroxylase is the rate-limiting step of serotonin synthesis, not to be confused with tyrosine hydroxylase.

Epinephrine and glucagon are examples of hormones that affect G protein-coupled receptors like adenylate cyclase and increase levels of cAMP. The other hormones listed affect receptor tyrosine kinases and non-receptor tyrosine kinases.

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.

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.

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

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.

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.

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.

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

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.

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

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.

In this question, all of the answer choices will be true except for one. Therefore, we'll need to consider each answer choice, one by one, in order to determine whether it is a true statement.

First, let's briefly recall the basics of G protein-coupled receptors (GPCRs). These receptors are located on the cell membrane, and work by binding to ligands on the extracellular side. This binding induces a conformational change in the receptor, which then activates a G protein on the inner membrane. This activated G protein becomes active by shedding the GDP it has bound, and in exchange it binds to a new GTP molecule. This newly activated G protein then goes on to activate another enzyme found within the cell membrane, called adenylyl cyclase. This enzyme, when activated this way, catalyzes the transformation of ATP into cyclic AMP (cAMP). This cAMP, in turn, acts as a second messenger and, in doing so, activates protein kinase A (PKA). PKA then goes on to phosphorylate a wide range of target proteins, which ultimately leads to a cellular response.

In addition, there are other types of GPCRs that lead to a different kind of signal transduction cascade. This alternative pathway involves the signaling molecules inositol triphosphate (IP3), diacylglycerol (DAG), and protein kinase C (PKC). But for the purposes of this question, we will focus on the one explained above.

G Protein cascades are one type of transduction pathway, and just like any other biological process, it is important that it is regulated. Therefore, when turn on, there needs to also be mechanisms in place to turn it off.

One of the ways in which the cascade is turned off is through the innate GTPase activity of the G proteins themselves. After a certain amount of time has passed, these G Proteins are able to hydrolyze their bound GTP into GDP, and in doing so, they become inactivated.

Another method used to turn off the pathway is through the combined action of beta-adrenergic receptor kinase and beta-arrestin. In this case, beta-adrenergic receptor kinase phosphorylates the receptor. This, in turn, attracts beta-arrestin to the receptor, which then physically blocks the receptor from interacting with G Proteins.

Additionally, the pathway can be turned once the extracellular ligand has fallen to a low concentration.

Yet another way that the pathway can be turned off is by the reduction in the second messenger cAMP. This is accomplished by the activity of a class of enzymes called the phosphodiesterases.

And lastly, phosphatases are enzymes which remove phosphate groups from their targets. As was mentioned above, the phosphorylation of GPCRs results in their inactivation. Therefore, if phosphate groups were to be removed from them, this would tend to have the opposite effect of activating them. Therefore, the action of phosphatases on GPCRs would not turn them off.

G protein-linked receptors are, indeed, the most commonly found in prokaryotes, and their polypeptide chain crosses the membrane seven times -- hence the alternate name, serpentine receptor. The G-protein is bound to the interior of the plasma membrane, sometimes, at least, in a complex with the receptor. G proteins do have three subunits, , , and . However, it is that releases GDP and binds GTP, dissociating the protein, with two resulting parts, an and a complex.

When a G-protein is activated (in its ATP bound state), the alpha subunit dissociates from the beta and gamma subunits and binds to the effector enzyme for further activation and signal amplification downstream. For example, when adrenaline binds to the beta-andrenergic receptor, the alpha subnit dissociates from the beta+gamma subunits and activates adenylyl cyclase, which then produces cAMP, signaling for downstream protein targets to be phosphorylated.

In its unactivated state, a G protein is present as a heterotrimer consisting of an alpha, a beta, and a gamma subunit. This heterotrimer is bound to GDP. Upon activation by conversion of GDP to GTP, the G protein will dissociate into an alpha subunit separated from the beta and gamma unit (these two are still connected).

In its unactivated state, a G protein is present as a heterotrimer consisting of an alpha, a beta, and a gamma subunit. This heterotrimer is bound to GDP. Upon activation by conversion of GDP to GTP, the G protein will dissociate into an alpha subunit separated from the beta and gamma unit (these two are still connected).

The alpha subunit of a G protein has intrinsic GTPase activity that, although slow, will automatically convert GTP back to GDP when the action of the G protein has finished.

Integrins have two subunits, alpha and beta. They do indeed bind the cell's cytoskeleton to its matrix, and can indicate to the cell the nature of that matrix. Integrins attach to a cell's actin and intermediate filaments. Blood platelets contain integrins, which bind proteins, like fibrinogen, in the matrix. This permits blood clotting, and the absence of certain integrins can cause a pathology in which people's blood does not clot well.

Transport proteins (such as the GLUT1 transporter) are asymmetric. They have two conformational states that accept the ligand from the extracellular environment and release it inside the cell after transport.