SECOND MESSENGER
SECOND MESSENGERS:
- Molecules relaying signals from membrane receptors to target molecules inside cells.
Common second messengers:
- Cyclic Adenosine 3′ 5′- Monophosphate (cAMP)
- Cyclic Guanosine Monophosphate (cGMP)
- Diacylglycerol (DAG)
- Calcium ions (Via Calmodulin)
- Inositol Triphosphate (IP3)
- Gaseous molecules – Nitric oxide (NO), Carbon-mono-oxide (CO) & Hydrogen Sulphite (H2S)
Note: NO acts as both 1° messenger (through cGMP) & 2° messenger.
CLASSIFICATION:
Group I hormones:
- Lipid soluble
- Readily diffuse across cell membrane .
- Directly bind to intracellular receptors.
- No need for second messenger.
Group II hormones:
- Most are polypeptides
- Water-soluble.Act on cell membrane receptors.
- Hence, cannot diffuse across cell membrane.
- Membrane receptors convey effector signals to target molecule via 2nd messenger.
- Hormone/Ligand – 1st messenger exerting its effects on 2nd messenger
MECHANISM OF ACTION:
1. Intracellular receptors:
- Stimulates transcription.
- Formation of mRNA translating into effector protein.
2. Secondary messengers of membrane receptors:
- Act by post-translational modification.
- Most predominant protein modification – “Phosphorylation”.
Cellular phosphorylation:
- Under control of 2 groups of protein –
1. Protein kinases –
- Enzymes adding/catalyzing phosphorylation tyrosine or serine or threonine residues in proteins
- 2nd messengers act on protein kinases stimulating protein phosphorylation.
2. Phosphatases I–
- Enzymes removing phosphates from protein (dephosphorylation).
CALMODULIN:
- Calcium-dependent regulatory protein is calmodulin
- Second messenger Ca2+ effects through calmodulin.
- Calmodulin- four Ca2+ binding sites & its full site occupancy leads to marked conformational change.
Functions of calmodulin:
- Marked conformational change allows calmodulin to activate enzymes & ion channels.
Important enzymes & proteins regulated:
- Adenylyl cyclase.
- Ca2+ dependent protein kinase.
- Ca2+-Mg2+ ATPase.
- Phosphodiesterase.
- Ion channels.
- Nitric acid synthase.
- Phosphorylase kinase.
Exam Important
SECOND MESSENGERS:
Common second messengers:
- Cyclic Adenosine 3′ 5′- Monophosphate (cAMP)
- Cyclic Guanosine Monophosphate (cGMP)
- Diacylglycerol (DAG)
- Calcium ions (Via Calmodulin)
- Inositol Triphosphate (IP3)
- Gaseous molecules – Nitric oxide (NO), Carbon-mono-oxide (CO) & Hydrogen Sulphite (H2S)
CLASSIFICATION:
Group I hormones:
- Directly binds to intracellular receptors.
Group II hormones:
- Acts on cell membrane receptors.
- Hormone/ligand is 1st messenger effecting on 2nd messenger
MECHANISM OF ACTION:
1. Intracellular receptors:
- Act by stimulation of transcription.
2. Secondary messengers of membrane receptors:
- Act by post-translational modification.
- Most predominant – “Phosphorylation”.
Cellular phosphorylation by,
1. Protein kinases –
- Enzymes catalyzing phosphorylation of tyrosine or serine or threonine residues in proteins.
- 2nd messengers act on protein kinases stimulating protein phosphorylation.
2. Phosphatases I–
- Enzymes removing phosphates from protein.
CALMODULIN:
- Calcium-dependent regulatory protein is calmodulin.
- Marked conformational change allows calmodulin to activate enzymes & ion channels.
Important enzymes & proteins regulated:
- Adenylyl cyclase.
- Ca2+ dependent protein kinase.
- Ca2+-Mg2+ ATPase.
- Phosphodiesterase.
- Ion channels.
- Nitric acid synthase.
- Phosphorylase kinase.



