ﻢﻴﺣﺮﻟا ﻦﻤﺣﺮﻟا ﷲا ﻢﺴﺑ - · PDF fileHow does cAMP act as a second messenger for hormonal action. ... Gi: Inhibits adenylate cyclase

بسم اهللا الرحمن الرحيمبسم اهللا الرحمن الرحيمبسم اهللا الرحمن الرحيمبسم اهللا الرحمن الرحيم

Dr. Hani Alrefai - 2014

Revision General functions of hormones. Hormone receptors Classification according to chemical nature Classification according to mechanism of action Compare and contrast between Hormones bind to

intracellular RCs and Hormones that bind cellmembrane receptor. Give (an) example(s) of: Hormone derived from steroids Small polypeptide Hormone

General functions of hormones. Hormone receptors Classification according to chemical nature Classification according to mechanism of action Compare and contrast between Hormones bind to

intracellular RCs and Hormones that bind cellmembrane receptor. Give (an) example(s) of: Hormone derived from steroids Small polypeptide Hormone


Dr. Hani Alrefai


ILOs How does cAMP act as a second messenger for

hormonal action. What are the types of G regulatory proteins and what

role do they play in hormonal mech. Of action The role of PKA in hormonal mech. Of action. Hormones acting through adenylate cyclase. NO

How does cAMP act as a second messenger forhormonal action. What are the types of G regulatory proteins and what

role do they play in hormonal mech. Of action The role of PKA in hormonal mech. Of action. Hormones acting through adenylate cyclase. NO


B) Hormones which bind to cellmembrane receptors

These hormones bind to their specific receptors onthe cell membrane.

This binding causes the formation of the secondmessenger

These hormones bind to their specific receptors onthe cell membrane.

This binding causes the formation of the secondmessenger



cAMP pathway


cAMP The hormone binds to its specific cell membrane

receptor. This binding activates a regulatory protein called G

protein. The active G protein activates or inhibits adenylate

cyclase enzyme. If adenylate cyclase is activated, it catalyses the

formation of cAMP from ATP. cAMP, through several steps, mediates the effects

of the hormone. Then cAMP is hydrolysed by phosphodiesterase

into AMP.

The hormone binds to its specific cell membranereceptor. This binding activates a regulatory protein called G

protein. The active G protein activates or inhibits adenylate

cyclase enzyme. If adenylate cyclase is activated, it catalyses the

formation of cAMP from ATP. cAMP, through several steps, mediates the effects

of the hormone. Then cAMP is hydrolysed by phosphodiesterase

into AMP.


cAMP pathway



A. G-regulatory protein This protein is so named because it binds to guanine

nucleotides: GDP or GTP. It consists of 3 polypeptide subunits (heterotrimeric

protein): α subunit, β subunit and γ subunit Under basal conditions the α subunit binds to GDP Binding of the hormone to its receptor activates G

protein through: Exchange of GDP and GTP on the α subunit.Dissociation of active α subunit from β- γ

subunits.

This protein is so named because it binds to guaninenucleotides: GDP or GTP. It consists of 3 polypeptide subunits (heterotrimeric

protein): α subunit, β subunit and γ subunit Under basal conditions the α subunit binds to GDP Binding of the hormone to its receptor activates G

protein through: Exchange of GDP and GTP on the α subunit.Dissociation of active α subunit from β- γ

subunits.


The active α subunit (α-GTP) affects the activity ofthe next reaction according to the type of G protein: Gs: Stimulates adenylate cyclase. Gi: Inhibits adenylate cyclase. Gq: Stimulates phospholipase C. Other types affect Ca channels and K channels.

The α subunit has intrinsic GTPase activity. After α subunit exerts its effects, GTPase hydrolyses its GTP

into GDP and Pi. The inactive α subunit (α –GDP) reassociates with the β- γ

subunits and remains inactive until reactivated again.

A. G-regulatory protein The active α subunit (α-GTP) affects the activity of

the next reaction according to the type of G protein: Gs: Stimulates adenylate cyclase. Gi: Inhibits adenylate cyclase. Gq: Stimulates phospholipase C. Other types affect Ca channels and K channels.

The α subunit has intrinsic GTPase activity. After α subunit exerts its effects, GTPase hydrolyses its GTP

into GDP and Pi. The inactive α subunit (α –GDP) reassociates with the β- γ

subunits and remains inactive until reactivated again.


B. Adenylate Cyclase enzyme Adenylate cyclase catalyses the formation of cAMP from ATP. Stimulation or inhibition of adenylate cyclase depends on

the type of activated G protein.

hormones activate adenylatecyclase

hormones inhibit adenylatecyclase

hormones activate adenylatecyclase

hormones inhibit adenylatecyclase

•FSH, LH, TSH, HCG.•Glucagons.•β catecholamines.•PTH and calcitonin.

•Somatostatin.•Angiotensin II.

•α2 catecholamines


C. Protein Kinase A cAMP dependent protein kinase A is a tetramer formed

of: 2 regulatory subunits (R). 2 catalytic subunits (C).

The R2C2 tetramer is inactive. On activation 4 cAMP molecules bind to the 2

regulatory subunits leaving the 2 catalytic subunits freeto act.

Active protein kinase transfers gamma phosphate groupfrom ATP to serine or threonine amino acid residues of aspecific protein causing its phosphorylation. The phosphorylated protein e.g. enzyme, mediates the

hormonal effect.

cAMP dependent protein kinase A is a tetramer formedof: 2 regulatory subunits (R). 2 catalytic subunits (C).

The R2C2 tetramer is inactive. On activation 4 cAMP molecules bind to the 2

regulatory subunits leaving the 2 catalytic subunits freeto act.

Active protein kinase transfers gamma phosphate groupfrom ATP to serine or threonine amino acid residues of aspecific protein causing its phosphorylation. The phosphorylated protein e.g. enzyme, mediates the

hormonal effect.


D. Phosphodiesterase After mediating its effects, cAMP is hydrolysed by

cAMP-dependent phosphodiesterase enzyme into5’AMP.

Phosphodiesterase is inhibited by methyl xanthines e.g.caffeine. So, they increase cAMP levels and prolong theaction of some hormones.

After mediating its effects, cAMP is hydrolysed bycAMP-dependent phosphodiesterase enzyme into5’AMP.

Phosphodiesterase is inhibited by methyl xanthines e.g.caffeine. So, they increase cAMP levels and prolong theaction of some hormones.



Cyclic GMP It is the second messenger of a group hormones called

“Atriopeptins” e.g. Atrial natriuretic factor (ANF). They cause:

1-Natiuresis 2-Diuresis 3-VD 4-Inhib. aldosterone sec.

Mechanism:Mechanism: The hormone binds to its specific receptor. Activates the membrane bound form of guanylate cyclase. Active guanylate cyclase catalyses the formation of cGMP from GTP. cGMP activates a cGMP-dependent protein kinase. The active protein kinase phosphorylates a number of proteins which

mediate the effects of atriopeptins. cGMP is then hydrolyzed by cGMP dependent phosphodiesterase

enzyme to 5’ GMP.

It is the second messenger of a group hormones called“Atriopeptins” e.g. Atrial natriuretic factor (ANF). They cause:

1-Natiuresis 2-Diuresis 3-VD 4-Inhib. aldosterone sec.

Mechanism:Mechanism: The hormone binds to its specific receptor. Activates the membrane bound form of guanylate cyclase. Active guanylate cyclase catalyses the formation of cGMP from GTP. cGMP activates a cGMP-dependent protein kinase. The active protein kinase phosphorylates a number of proteins which

mediate the effects of atriopeptins. cGMP is then hydrolyzed by cGMP dependent phosphodiesterase

enzyme to 5’ GMP.


Nitric Oxide (NO) Certain compound such as Nitric oxide, nitroglycerine,

nitroprusside, sodium azide and sodium nitrite cause: Smooth muscle relaxation. Vasodilatation.

These compounds use a common mechanism bystimulating the soluble cytosolic form of guanylatecyclase.

Certain compound such as Nitric oxide, nitroglycerine,nitroprusside, sodium azide and sodium nitrite cause: Smooth muscle relaxation. Vasodilatation.

These compounds use a common mechanism bystimulating the soluble cytosolic form of guanylatecyclase.


Nitric Oxide (NO)Synthesis (Site) Endothelial cells

Synthesis (enzyme) NO synthetase

Synthesis (precursor) Arginine ----------→ NO + citrulline

Site of action Adjacent smooth muscles

Second messenger cGMPSecond messenger cGMP

Protein kinas cGMP dependent protein kinase

End pathway effect phophorylates certain muscle proteins

Physiological effects •Regulation of blood pressure.•Smooth muscle relaxation•Neurotransmitter in brain andperipheral autonomic nervous system.•Inhibits aggregation of platelets.



بسم اهللا الرحمن الرحيمبسم اهللا الرحمن الرحيمبسم اهللا الرحمن الرحيمبسم اهللا الرحمن الرحيم


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ﻢﻴﺣﺮﻟا ﻦﻤﺣﺮﻟا ﷲا ﻢﺴﺑ - · PDF fileHow does cAMP act as a second messenger for hormonal action. ... Gi: Inhibits adenylate cyclase