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 - 2014
Dr. Hani Alrefai
Dr. Hani Alrefai - 2014
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
Dr. Hani Alrefai - 2014
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
Dr. Hani Alrefai - 2014
Dr. Hani Alrefai - 2014
cAMP pathway
Dr. Hani Alrefai - 2014
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.
Dr. Hani Alrefai - 2014
cAMP pathway
Dr. Hani Alrefai - 2014
Dr. Hani Alrefai - 2014
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.
Dr. Hani Alrefai - 2014
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.
Dr. Hani Alrefai - 2014
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
Dr. Hani Alrefai - 2014
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.
Dr. Hani Alrefai - 2014
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.
Dr. Hani Alrefai - 2014
Dr. Hani Alrefai - 2014
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.
Dr. Hani Alrefai - 2014
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.
Dr. Hani Alrefai - 2014
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.
Dr. Hani Alrefai - 2014
Dr. Hani Alrefai - 2014
بسم اهللا الرحمن الرحيمبسم اهللا الرحمن الرحيمبسم اهللا الرحمن الرحيمبسم اهللا الرحمن الرحيم
Dr. Hani Alrefai - 2014