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.

Phospholipase C catalyses the formation of DAG (diacylglycerol) and IP3 (inositol triphosphate) from PIP2 (phosphatidylinositol-4,5-bisphosphate). IP3 promotes the influx of calcium ions into the cytoplasm while DAG stimulates protein kinase C.

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.

In this question, we're asked to identify a statement that is not connected with intracellular signal transduction pathways (STP). To do so, we'll need to look at each answer choice individually.

Upon binding of a ligand to a G protein-coupled receptor (GPCR), the conformational change of this receptor is transmitted to a G-protein that is on the inner leaflet of the plasma membrane. This causes the individual sub-units of the G-protein to dissociate from each other, which then goes on to activate other components of the signal transduction pathway.

Activation of GPCR can also result in a signal transduction pathway in which a particular intracellular enzyme is activated. This enzyme is responsible for cleaving a specific fatty acid off of certain phospholipids from the plasma membrane. The fatty acid cleaved off is called phosphatidylinositol bisphosphate, which acts as a second messenger in STP's.

Another consequence of the activation of certain GPCR's is the activation of an enzyme called protein kinase A (PKA). This enzyme then goes on to phosphorylate other kinase enzymes. The end result is amplification of the entire signal.

One of the common second messengers in STP's is cyclic AMP (cAMP) and cyclic GMP (cGMP). One of the mechanisms in place to turn STP's off is to degrade these cyclic nucleotides. The class of enzymes responsible for this is called phosphodiesterases.

Beta-hydroxybutyrate is a ketone body that forms when excess acetyl-CoA is present. This molecule is not involved in signal transduction pathways.

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. 

Steroid hormones are nonpolar molecules that can travel across the hydrophobic (or nonpolar) interior of the plasma membrane whereas peptide hormones are polar molecules that cannot travel across the hydrophobic interior. The question states that the hormone cannot enter the cell. This means that it cannot traverse the plasma membrane and, therefore, must be a peptide hormone. A peptide is made up of several amino acids. There are polar and nonpolar amino acids. Since they are polar, peptide hormones must have at least a few polar amino acids. These polar amino acids can be positively charged, negatively charged, or uncharged. There are twelve polar amino acids, five of which are charged (aspartic acid, glutamic acid, histidine, lysine, and arginine). Aspartic acid and glutamic acid are negatively charged at physiologic pH, whereas the other three are positively charged. A molecule that forms clumps in water is hydrophobic and nonpolar. Since we are dealing with a peptide hormone, the hormone will dissolve and not form clumps in water. A steroid hormone, on the other hand, is nonpolar and will form clumps in water.

A hormone is a signaling molecule that binds to a receptor and initiates a signaling cascade inside the cell. The receptor for a hormone can be found on the periphery of the cell (on plasma membrane) or inside the cell (cytoplasm or nucleoplasm). A steroid hormone is nonpolar and can traverse the hydrophobic interior of the plasma membrane whereas a peptide hormone is polar and cannot traverse the hydrophobic interior; therefore, a steroid hormone will have its receptor inside the cell whereas a peptide hormone will have its receptor on the plasma membrane. The question is asking us to find the polar, peptide hormone (because its receptor will be found on the plasma membrane, not in cytoplasm). To answer this question, we need to know which amino acids are polar. Recall that there are twelve polar amino acids. They are serine, threonine, cysteine, tyrosine, asparagine, glutamine, aspartic acid, glutamic acid, histidine, lysine, and arginine; therefore, the hormone containing phenylalanine, histidine, and methionine is most likely to be polar. The rest of the hormones have nonpolar amino acids only.

Peptide hormones are polar molecules that cannot traverse the plasma membrane. Recall that plasma membranes have a hydrophobic interior. Since peptide hormones are polar, they cannot travel through this hydrophobic interior of the plasma membrane; therefore, peptide hormones signal cells by binding to receptors on the plasma membrane. There are several types of hormone receptors on the membrane, including G protein coupled receptors and receptor tyrosine kinases. Upon binding, the receptors activate themselves and other intracellular molecules called second messengers. This leads to a signaling cascade that ultimately results in upregulation or downregulation of processes inside the cell. Second messenger molecules facilitate the amplification and propagation of signal throughout the cell. Cyclic adenosine monophosphate, or cAMP, is one of the most common second messenger molecules; therefore, all three molecules listed in this question are involved in peptide hormone pathway.

Insulin promotes the translocation of GLUT-4 receptors to the cell surface through cell signaling triggered by its binding to cell surface insulin receptors. GLUT-2 transporters are insulin-independent and are found in tissues like the pancreas and liver where immediate glucose sensing is important for whole body function (The pancreas needs to sense glucose so it can secrete insulin for the rest of the body. Imagine if the pancreas itself needed insulin.)

Glucagon and epinephrine are typically thought of as having catabolic effects; however, their purpose is to increase the availability of fuel substrates to extra-hepatic tissues during the fasting state or during fight or flight situations, respectively. So, while many of their effects like glycogenolysis and lipolysis conform to this pattern, they also induce the anabolic process of gluconeogenesis in the liver to increase the availability of glucose to other tissues.