Revision. General functions of hormones. Hormone receptors. Hormone derived from steroids Small polypeptide Hormone
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1 االله الرحمن الرحيم بسم
2 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 cell membrane receptor. Give (an) example(s) of: Hormone derived from steroids Small polypeptide Hormone
3 Dr. Hani Alrefai
4 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 role do they play in hormonal mech. Of action The role of PKA in hormonal mech. Of action. Hormones acting through adenylate cyclase. NO
5 B) Hormones which bind to cell membrane receptors These hormones bind to their specific receptors on the cell membrane. the cell membrane. This binding causes the formation of the second messenger
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7 camp pathway
8 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.
9 camp pathway
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11 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 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.
12 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.
13 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 adenylate cyclase FSH, LH, TSH, HCG. Glucagons. β catecholamines. PTH and calcitonin. hormones inhibit adenylate cyclase Somatostatin. Angiotensin II. α2 catecholamines
14 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 free to act. Active protein kinase transfers gamma phosphate group from ATP to serine or threonine amino acid residues of a specific protein causing its phosphorylation. The phosphorylated protein e.g. enzyme, mediates the hormonal effect.
15 D. Phosphodiesterase After mediating its effects, camp is hydrolysed by camp-dependent phosphodiesterase enzyme into 5 AMP. Phosphodiesterase is inhibited by methyl xanthines e.g. caffeine. So, they increase camp levels and prolong the action of some hormones.
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17 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: 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.
18 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 by stimulating the soluble cytosolic form of guanylate cyclase.
19 Nitric Oxide (NO) Synthesis (Site) Synthesis (enzyme) Synthesis (precursor) Site of action Second messenger Protein kinas End pathway effect Physiological effects Endothelial cells NO synthetase Arginine NO + citrulline Adjacent smooth muscles cgmp cgmp dependent protein kinase phophorylates certain muscle proteins Regulation of blood pressure. Smooth muscle relaxation Neurotransmitter in brain and peripheral autonomic nervous system. Inhibits aggregation of platelets.
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21 االله الرحمن الرحيم بسم
Revision. camp pathway
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