Second Messengers - Biochemistry

Nitric oxide is a gas second messenger.It is also a neurotransmitter in the brain. Nitric oxide is produced by 3 enzymes: endothelial, induced, and neuronal nitric oxide synthases. Nitric oxide synthases require a calcium ions for the enzyme activity. Nitric oxide does act thru the cyclic guanosine monophosphate activation pathway.

Signaling receptors can be divided into two categories: ion channels and second-messenger utilizing receptors. Ion channels are activated by voltage changes (voltage-gated) or ligand binding (ligand-gated) and they tend to increase the flow of ions into and outside of cell. Receptors, such as G protein-coupled receptors, are activated by ligand binding; however, they signal the cell by activating second messenger molecules such as cAMP.

Receptor tyrosine kinase pathway utilizes second messenger molecules to activate molecules in the cell that, subsequently, activate cellular mechanisms. Ion channels allow for flow of ions between membranes; they do not directly activate second messenger molecules.

cAMP is a second messenger molecule that activates several molecules. Second messenger molecules often amplify the original signal, allowing for the signal to travel all across the cell. One of the molecules activated by cAMP is protein kinase C (PKC). This molecule, as the name implies, is a kinase; therefore, it phosphorylates other molecules. Note that this is a function of protein kinase C, not a direct function of cAMP.

With an inhibitory G protein, the binding of a ligand and stimulation of the receptor will activate the alpha subunit of the G protein, however since it is an inhibitory G protein, it will not go on to activate adenyl cyclase. With no activation of Adenyl cyclase it will lead to decrease cAMP and other secondary messengers.

Guanylyl cyclase is the enzyme responsible for catalyzing this reaction, and the reaction involves removing two phosphate groups from guanosine triphosphate to generate cyclic guanosine monophosphate. Adenylyl cyclase performs a similar reaction but the substrate is adenosine triphosphate and the product is cyclic adenosine monophosphate. cGMP protein kinase is a target that is activated by cGMP, but is not involved in this reaction.

PIP2 gets cleaved into two smaller molecules by phospholipase C, and these two molecules are DAG and IP3. The protein kinases are not produced from this reaction, nor is cAMP or phosphatidylcholine. This is simply a matter of knowing that DAG and IP3 are the two most important lipid-derived second messengers.

Once the conformation change has been induced by ligand binding, the GPCR can act as a guanine exchange factor (GEF) which exchanges out a bound GDP (lower energy) on the G-protein for a GTP (higher energy). This triggers the dissociation of the G-protein, and it goes on to activate various second messenger cascades within the cell. Generally, addition of phosphate groups in biochemistry signals "activation," and removal triggers "deactivation."

All of the hormones, and tissues, listed, have responses which can be mediated by cyclic AMP. Luteinizing hormone, however, does not target the heart. Rather, it targets organs of the reproductive system.

The binding of four cAMP molecules to PKA dissociates it into two regulatory subunits and two catalytic subunits. The actual sites that the cAMP binds to, however, are allosteric sites - they are not directly on the regulatory sites or the catalytic sites.

There are many types of second messengers including diacylglycerol, cAMP, cGMP, calcium, and inositol trisphosphate. However, a G-protein is part of a pathway that utilizes second messengers, but is not one itself.

The function of phospholipase C is to cleave phosphatidylinositol biphosphate (PIP2) into the two second messenger molecules, diacylglycerol (DAG) and inositol triphosphate (IP3). These can then act within signal transduction pathways to amplify ligand/receptor signals.

A phosphorylation cascade, involves many different steps and complicated interactions between kinases, phosphorylases, and phosphatases. In this case, the enzymes mentioned relate to the phosphorylation and dephosphorylation cascade involved with glycogen synthesis and degradation.

When a beta-adrenergic receptor or glucagon receptor is activated, two types of G-protein couple receptors, a G-protein is phosphorylated and disassociates GTP to act upon the enzyme, Adenylate cyclase, to synthesize cylic AMP (cAMP) from ATP.

This first step following the release of cAMP is that it acts upon protein kinase A by attaching to its two R subunits (requiring 4 cAMP) while releasing two C subunits. The C subunits function as other chemical messengers in the cell, acting upon multiple different enzymes to ultimately increase the rate of glycogen degradation and decrease the rate of glycogen synthesis.

Second messengers are molecules that act within cells to either increase or decrease activity or amount of a final molecule. All of the answer choices are second messengers in various pathways.

When a ligand binds to its associated receptor, the signal is passed into the cell and on to a distinct final molecule (often DNA transcription factors). Second messengers allow for significant amplification of a single ligand/receptor signal in order to cause mass change within a cell, and therefore within the body.

Often following the activation of a G protein, ATP is converted to the second messenger, cAMP, by adenylate cyclase. This propagates the amplification of the signal transduction.

After adenylate cyclase converts ATP to cAMP, this second messenger goes on to bind to protein kinase A. Unactivated protein kinase A requires cAMP in order to become activated, at which point it can phosphorylate certain threonine and serine residues on target molecules.

In order for protein kinase A to become activated, cAMP must bind to it. PKA has a structure composed of two regulatory subunits and two catalytic subunits all bound together. The catalytic units are active on their own, so in order to work they must simply become dissociated from the regulatory subunits. Thus, cAMP will bind to only the regulatory subunits of PKA which then allows dissociation of the already catalytic subunits.

Atrial natriuretic factor (ANF) and nitric oxide use cGMP as a second messenger to exert their effects. The ANF has guanylyl cyclase activity which converts GTP (guanosine-5'-triphosphate) to cGMP (cyclic guanosine monophosphate). This in turn activates protein kinase G and leads to relaxation of smooth muscle. IP3, calcium and DAG are second messengers in activation pathways of G protein-coupled receptors, as is the case of the epinephrine receptor.