WITH THE NAME OF ALLAH THE MOST GRACIOUS AND THE MOST MERCIFUL.

Cyclic AMP pathway and regulation

Presented by RIDA MASOOM & SAIMA TUFAIL.
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STRUCTURE OF CYLIC AMP

In the structure of ribose sugar the phosphate molecule is attached in cyclic manner b/w C3-C5.

HOW CYCLIC AMP IS FORMED

In the second messenger mechanism cyclic AMP is formed due to the activation of adenylyl cyclase enzyme by the action of alpha subunit due to incorporation of GTP.

 SECOND MESSENGER SYSTEM

The system for the transportation of second messengers with in the cell.

SECOND MESSNGER
It intervene between the origional messenger and have an ultimate effect on the cell.

TYPES
Calcium or phosphatidylinositol system Adenylyl cyclase system

ADENYLYL CYLASE
This is a membrane bounded enzyme which converts ATP to 3,5 adenosine monophosphate(cAMP). Recognition of Chemical signals due to Alpha and beta andrenergic receptors either increase or decrease the activity of adenylyl cyclase.
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AYDENYLYL CYCLASE
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 There are G protein coupled receptor are present on membrane (GPCR) GPCR is characterized by an extracellular ligand - binding region , seven transmembrane helices,and an intercellular domain that interact with Gprotein.

Structure of GPCR
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GTP-DEPENDENT REGULATORY PROTEIN

Action of GPCR on second messenger formation is mediated by trimeric proteins(alpha , beta , gemma subunits) of cell membrane. These proteins are called G-proteins because they bind with guanosine nucleotide. It form a link in the chain of communication between the receptor and adenylyl cyclase.
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 Inactive form of alpha-subunit bind to GDP and there is a conformational change in the structure of receptor. GDP is converted into GTP. GTP-bound form of alpha-subunit dissociates from the beta,gemma subunit to adenylyl cyclase which is there by activated. The action of Galpha-GTP complex are short lived due to inherent GTPase. Adenylyl cyclase in active form convert ATP into cAMP.

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FAMILY OF G-PROTEIN
Gs,Gq (stimulates the enzymes) Gi (inhibits the enzyme)

For example
Vibrio cholera inhibit the GTPase activity of Gs. Bordetella pertussis (whooping cough) inhibit the Gi.

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FUNCTIONS OF CYCLIC AMP

It activates protein kinase A by binding to its regulatory subunit. The active subunit catalyze the transfer of phosphate from ATP to specific serine or therionine. This phosphorylated protein directly acts on cell membrane channels. If these proteins are enzymes these can be activated or inhibited. protein kinase A can also phosphorylate the protein which binds to DNA and cause change in gene expression.

Note
several types of protein kinases are not cAMP dependent like protein kinase C.

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cAMP PATHWAY
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HYDROLYSIS OF CYCLIC AMP

Cyclic AMP is rapidly hydrolyzed to 5-AMP by cAMP phosphodiesterase. cAMP phosphodiesterase is an enzyme which cleave the cyclic 3,5phosphodiester bond. Increase of cAMP is terminated if extracellular signal are remove(hormone or neurotransmittors).

Note
Phosphodieserase is inhibited by methyxanthine derivative, such as theophylline and caffeine.

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HYDROLYSIS OF cAMP

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REGULATION OF cAMP
As long as stimulus is attached to the receptor site of the binding proteins outside domain the alpha subunit of Gprotein remains active. Active alpha subunit have inherit GTPase activity. It regulates itself.

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ANY QUESTION?
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QUESTIONS???
Q.1 The structure of G protein consists of extracellular domain for .. ? 1. Binding with G-protein 2. Binding with adenylyl cyclase 3. Binding with 1st messenger 4. Binding with 2nd messenger correct option is 3. Q. 2 Second messenger formation is mediated by.? 1. Trimeric protein 2. G protein 3. Alpha,beta,gamma subunits 4. All are correct Correct option is 4

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Q.3 A membrane bound enzyme that convert ATP into cyclic AMP 1. Phosphokinase A 2. Phosphokinase C 3. GTPase 4. Adenylyl cyclase Correct option is 4. Q.4 cAMP is hydrolysed by the enzyme phosphodiesterase which is inhibited by 1. Methylxanthine 2. Theophylline 3. Caffeine 4. All are correct. The correct option is 4.

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Q.5 Function of cAMP is..?

1. Protein kinase C is activated 2. Dephosphorylated protein act directly on ion channels 3. Protein kinase A bind to specific protein that binds to DNA 4. Activates to protein kinase A by binding with its functional unit Correct option is 3.
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