secondary messengers

types and pathway of secondary messengers.

1. SECONDARY MESSENGERS PATHWAY

2. INDEX INTRODUCTION TYPES OF SECONDARY MESSENGERS COMMON PATHWAYS OF SECONDARY MESSENGERS IP3-DAG SECONDARY MESSENGER CALCIUM ION AS A SECONDARY MESSENGER NITRIC OXIDE REFERENCES

3. INTRODUCTION G eneration of small intermediate, rapidly diffusing molecules by cells referred to as secondary messenge. They follow the Signal transduction pathways. They cause changes in the activities of cell. Removal of secondary messenger terminates the cellular response. Secondary messengers are discovered by Earl Wilbur Sutherland, Jr There e are 3 major classes of second messengers: C yclic nucleotides (e.g., cAMP and cGMP) I nositol trisphosphate (IP 3 ) and diacylglycerol (DAG) C alcium ions (Ca 2+ )

4. TYPES OF SECONDARY MESSENGERS HYDROPHOBIC- water-insoluble molecules, diffuse from th e  plasma membrane into the intermembrane space . HYDROPHILIC- water-soluble molecules,located within the cytosol . GASES - can diffuse both through cytosol and across cellular membrane .  HYDROPHOBIC HYDROPHILIC GASES Diacylglycerol(DAG) cAMP, cGMP Nitrous Oxide Phosphatidylinositol IP3 Hydrogen Sulfide Calcium Ion Carbon Monoxide

5. COMMON PATHWAYS OF SECONDARY MESSENGERS Three classic second messenger pathways are illustrated in the picture;

6. CONTINUED... A ctivation of adenylyl cyclase by G-protein-coupled receptors (GPCRs) to generate the cyclic nucleotide second messenger 3′- 5′-cyclic adenosine monophosphate (cAMP) . S timulation of phosphoinositide 3-kinase (PI3K) by growth factor receptors to generate the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ). A ctivation of phospholipase C by GPCRs to generate the two second messengers membrane-bound messenger diacylglycerol (DAG) and soluble messenger inositol 1,4,5-trisphosphate (IP 3 ) . And then binds to receptors on subcellular organelles to release calcium into the cytosol.

7. IP3-DAG SECONDARY MESSENGER IP3-DAG produced by the hydrolysis of PIP2(Phosphatidylinositol 4,5-biphosphate) . PLC(Phospholipase C) is the lead component in the hydrolysis of PIP2 . IP3 diffuses through the cytosol & bind to receptor on the endoplasmic reticulum(ER) . At endoplasmic reticulum (ER) it binda to the IP3 gated calcium ion channel . DAG stimulates protein kinase C (PKC) by increasing the affinity of enzyme for calcium ion. Known target protein include calmodulin , the glucose transporter, cytochrome P450 .

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9. CALCIUM ION AS SECONDARY MESSENGERS Calcium ion released from the ER they enter the cytoplasm & exerts allosteric regulatory effect on many enzyme and protein. Low cytoplasmic Ca ++ at rest (10-100nM) , sudden increase in cytoplasmic Ca ++ level upto 500-1000nm . Low concentration of Ca ++ is maintained by pumping from cytosol to the extracellular space. Ca ++ act as a secondary messenger In two ways; Bind to an effector cell(e.g. Enzyme ) Bind to cytosolic calcium binding protein (e.g. Calmodulin CaM ) Most of the Ca ++ medicated event occurs when C ++ bind and activate the regulatory protein Calmodulin . Besides, calmodulin there are other C ++ binding protein (e.g. Troponin C). Binding of C ++ cause profound confirmation change in calmodulin (CaM).

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11. NITRIC OXIDE NO is a unique messenger. It is a gas, although it does dissolve in an aqueous solution. NO does not require energy to transport itself in and out the cell. NO functions within the cell that produces it as a second messenger. It functions as a paracrine molecule able to travel 10–20 cell diameters to regulate the biology in adjacent cells. NO is a simple gas and it is able to alter the activity of intracellular target enzyme . It is synthesized from arginine & oxygen by the NO Synthases . The endothelium (inner line) of blood vessels use NO to signal the surrounding smooth muscle results in vasodilation.

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13. CONTINUED... Acetylcholine is released from the terminus of nerve cell in the blood vessel wall. Acetylcholine acts on endothelial cell to stimulate NO synthesis(by arginine). NO diffuse to neighbours smooth muscle cell where it interact with guanylyl cyclase. Stimulate the synthesis of cGMP. The cGMP than induce the muscles relaxation and blood vessel dilation.

14. REFERENCES https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968160/ https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Biology_(Kimball)/04%3A_Cell_Metabolism/4.14%3A_Secondary_Messengers http://www.slideshare.net/drpriya07/slideshare-second-messengers-aj?from_m_app=android https://www.news-medical.net/life-sciences/PIP2-signal-pathway.aspx https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678935/

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