cAMP Full Form: Targets of cAMP
cAMP generated by adenylyl cyclase has 3 major targets:
- The cyclic AMP-dependent protein kinase (PKA)
- cAMP-regulated guanine nucleotide exchange factors termed EPACs (Exchange protein directly activated by cAMP)
- via PKA phosphorylation, a transcription factor named CREB (cAMP response element-binding protein)
cAMP Full Form: Mode of Action
- cAMP is a second messenger, synthesized by ATP by the enzyme adenylyl cyclase.
- Adenylate cyclase is activated by stimulatory G (Gs) protein-coupled receptors.
- Inhibited by adenylate cyclase inhibitory G (Gi) protein-coupled receptors.
- Inactive PKA is a tetramer that consists of two regulatory (R) subunits and two catalytic (C) subunits.
- Each R subunit contains a pseudosubstrate domain whose sequences resemble that of a peptide substrate and binds to the active site in the catalytic domain but are not phosphorylated.
- Thus, this pseudosubstrate domain inhibits the activity of catalytic subunits.
- Inactive PKA is turned on through the binding of cAMP
- Each R subunit has two distinct cAMP-binding sites, called CNB-A and CNB-B
- The binding of cAMP to both sites causes a conformational change in the R subunit. including its pseudosubstrate domain so that it can no longer bind to and inhibit the catalytic domain.
- Thus, the kinase activity is activated.
- The binding of cAMP by an R sub-unit of PKA occurs cooperatively.
- The binding of the first cAMP molecule to CNB-Blowers the Kd for binding the second cAMP to CNB-A.
- Thus, small changes in the level of cytosolic cAMP can cause proportionately large changes in the number of dissociated C subunits and hence in cellular kinase activity.
cAMP Full Form: Regulation of Glycogen Metabolism By cAMP and PKA
I. Effect of increase in cAMP:
- An increase in cytosolic cAMP activates PKA
- PKA phosphorylates glycogen synthase
- This leads to inhibition of glycogen synthesis.
- Active PKA also promotes glycogen degradation via a protein kinase cascade.
- At high cAMP conc, PKA phosphorylates an inhibitor of phosphoprotein phosphatase (PP)
- The binding of the phosphorylated inhibitor to PP prevents this phosphatase from de-phosphorylating the activated enzymes in the kinase cascade or the inactive glycogen synthase.
II. Effect of decrease in cAMP
- Decrease in cAMP inactivates PKA
- This leads to the release of the active form of PP
- The activation of PP promotes glycogen synthesis and inhibits glycogen degradation
- PKA mediates a large array of hormone-induced cellular responses in multiple tissues.
cAMP Full Form: Inhibition of cAMP
- cAMP decomposition into AMP is catalyzed by the enzyme phosphodiesterase
- They work by hydrolyzing the cyclic 3’,5’-phosphodiester bond in cAMP and cGMP; thereby terminating the action.
cAMP Full Form: Role of cAMP in Lac Operon
A. Positive regulation of lac operon:
- When lactose is present, but glucose is absent.
- A protein called Catabolite Activator Protein (CAP) binds with cAMP to form a CAP-cAMP complex.
- The CAP protein is a dimer of two identical polypeptides
- Next, the CAP-cAMP complex binds to the CAP site which is upstream of the site where RNA Polymerase binds to the promoter.
- CAP then recruits RNA polymerase to the promoter and then transcription is initiated.
B. Negative regulation of lac operon:
- When glucose is present along with lactose, glucose is preferentially used because catabolite repression (also called the glucose effect) occurs.
- In catabolite expression, the lac operon is expressed only at very low levels of lactose present in the medium.
- This is because glucose causes the amount of cAMP in the cell to be reduced greatly.
- Thus, insufficient CAP-cAMP complex is available to recruit RNA Polymerase to the lac promoter, and thus transcription of lac operon takes place at a very low level.
- Thus, RNA Polymerase cannot bind to the promoter efficiently without the aid of the CAP-cAMP complex.
- Thus, cAMP plays a crucial role in catabolite repression.
cAMP Full Form: Functions of cAMP
Hormone inducing Rise in cAMP
Epinephrine; ACTH; glucagon
Increase in the hydrolysis of triglyceride; decrease in amino acid uptake
Epinephrine; norepinephrine; glucagon
Increase in the conversion of glycogen to glucose, inhibition of glycogen synthesis; increase in amino acid uptake; increase in gluconeogenesis (synthesis of glucose from amino acids)
Increase in the synthesis of estrogen, progesterone
Increase in the synthesis of aldosterone, cortisol
Increase in contraction rate
Secretion of thyroxine
Increase in resorption of calcium from bone
Conversion of glycogen to glucose-1-phosphate
Resorption of water
Inhibition of aggregation and secretion