This document discusses secondary messengers, which are small molecules that transmit signals within cells during signal transduction. There are three major classes of secondary messengers: cyclic nucleotides, inositol trisphosphate and diacylglycerol, and calcium ions. These messengers are generated through pathways such as G protein-coupled receptor activation of phospholipase C, which produces IP3 and DAG from PIP2. IP3 triggers calcium release from intracellular stores, while DAG activates protein kinase C. Calcium then acts as a messenger by binding to and activating proteins like calmodulin. Nitric oxide is also discussed as a gaseous messenger.

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
• Generation 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
• Theree are 3 major classes of second messengers:
1. Cyclic nucleotides (e.g., cAMP and cGMP)
2. Inositol trisphosphate (IP3) and diacylglycerol (DAG)
3. Calcium ions (Ca2+)

4. TYPES OF SECONDARY MESSENGERS
• HYDROPHOBIC-water-insoluble molecules, diffuse from the 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...
1) Activation of adenylyl cyclase by G-protein-coupled receptors (GPCRs) to
generate the cyclic nucleotide second messenger 3′-5′-cyclic adenosine
monophosphate (cAMP).
2) Stimulation of phosphoinositide 3-kinase (PI3K) by growth factor receptors to
generate the lipid second messenger phosphatidylinositol 3,4,5-
trisphosphate (PIP3).
3) Activation of phospholipase C by GPCRs to generate the two second
messengers membrane-bound messenger diacylglycerol (DAG) and soluble
messenger inositol 1,4,5-trisphosphate (IP3).
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.
Ligand+Re-
ceptor(GP
CR)
G-protein
Phospholi-
paseC
(PLC)
PIP2 IP3+DAG

8. CONTINUED...

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;
1. Bind to an effector cell(e.g. Enzyme)
2. 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).

10. CONTINUED...

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.

12. CONTINUED...

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/Boo
k%3A_Biology_(Kimball)/04%3A_Cell_Metabolism/4.14%3A_Secondary_Messe
ngers
• 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/

15. THANK YOU