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Hormones and Signal Transduction
Dr. Kevin Ahern
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Signaling• Outline
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Signaling• Outline
Background
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Signaling• Outline
BackgroundMembranes
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Signaling• Outline
BackgroundMembranesHormones & Receptors
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Signaling• Outline
BackgroundMembranesHormones & ReceptorsSecond Messengers
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Signaling• Introduction
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Signaling• Introduction
Needs of a Multicellular Organism
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Signaling• Introduction
Needs of a Multicellular OrganismResponding to Environment
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Signaling• Introduction
Needs of a Multicellular OrganismResponding to EnvironmentFood Status
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Signaling• Introduction
Needs of a Multicellular OrganismResponding to EnvironmentFood StatusDanger
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Signaling• Introduction
Needs of a Multicellular OrganismResponding to EnvironmentFood StatusDangerGrowth
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Signaling• Introduction
Needs of a Multicellular OrganismResponding to EnvironmentFood StatusDangerGrowthInjury
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Signaling• Introduction
Coordination of Cellular/Tissue Responses
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Signaling• Introduction
Coordination of Cellular/Tissue Responses
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Signaling
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Signaling• Membranes
Organization of Bilayer Around Cell
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Signaling• Membranes
Lipid Bilayer Prevents Entry of Most Molecules
Organization of Bilayer Around Cell
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Signaling• Membranes
Lipid Bilayer Prevents Entry of Most Molecules
Lipid Bilayer
Organization of Bilayer Around Cell
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Signaling• Membranes
Lipid Bilayer Prevents Entry of Most Molecules
Lipid Bilayer
Organization of Bilayer Around Cell
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Signaling• Membranes
Lipid Bilayer Prevents Entry of Most Molecules
Lipid Bilayer
Organization of Bilayer Around Cell
Information must move across membrane
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Signaling• Membranes
Lipid Bilayer Prevents Entry of Most Molecules
Lipid Bilayer
Organization of Bilayer Around Cell
Information must move across membraneSignal Transduction
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Signaling
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Signaling Simplest Signaling
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Signaling Simplest Signaling
Signal
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Signaling Simplest Signaling
Signal Response
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Nerve System Signaling
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Hormones and Signal Transduction• Hormones
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Hormones and Signal Transduction• Hormones
Hormones Communicate Messages
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Hormones and Signal Transduction• Hormones
Hormones Communicate MessagesHormones are Made in One Part of the Body
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Hormones and Signal Transduction• Hormones
Hormones Communicate MessagesHormones are Made in One Part of the BodyExert Effects in Other Part of Body
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Hormones and Signal Transduction• Hormones
Hormones Communicate MessagesHormones are Made in One Part of the BodyExert Effects in Other Part of BodyFirst Messengers of a Multi-component Message
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Hormones and Signal Transduction• Hormones
Hormones Communicate MessagesHormones are Made in One Part of the BodyExert Effects in Other Part of BodyFirst Messengers of a Multi-component MessageNumerous Chemical Forms
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Hormones and Signal Transduction• Hormones
Hormones Communicate MessagesHormones are Made in One Part of the BodyExert Effects in Other Part of BodyFirst Messengers of a Multi-component MessageNumerous Chemical Forms
Thyroid Hormone
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Hormones and Signal Transduction• Hormones
Hormones Communicate MessagesHormones are Made in One Part of the BodyExert Effects in Other Part of BodyFirst Messengers of a Multi-component MessageNumerous Chemical Forms
Epinephrine
Thyroid Hormone
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Hormones and Signal Transduction• Hormones
Hormones Communicate MessagesHormones are Made in One Part of the BodyExert Effects in Other Part of BodyFirst Messengers of a Multi-component MessageNumerous Chemical Forms
Epinephrine
Thyroid Hormone
Epidermal Growth Factor
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Hormones and Signal Transduction• Hormones
Hormones Communicate MessagesHormones are Made in One Part of the BodyExert Effects in Other Part of BodyFirst Messengers of a Multi-component MessageNumerous Chemical Forms
Epinephrine
Thyroid Hormone
Epidermal Growth Factor
Progesterone
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Hormones and Signal Transduction• Introduction
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Hormones and Signal Transduction• Introduction
Cellular Signaling Has Complexity
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Hormones and Signal Transduction• Introduction
Cellular Signaling Has Complexity Responses Aimed at Benefitting Organism
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Hormones and Signal Transduction• Binding to Receptor
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Hormones and Signal Transduction• Binding to Receptor
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Hormones and Signal Transduction• Binding to Receptor
Steroid Hormones Diffuse Through Membrane
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Hormones and Signal Transduction• Binding to Receptor
Steroid Hormones Diffuse Through MembraneCytosolic Receptor
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Hormones and Signal Transduction• Binding to Receptor
Steroid Hormones Diffuse Through MembraneCytosolic Receptor
Receptor Binding Inside Cell
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Hormones and Signal Transduction• Binding to Receptor
Steroid Hormones Diffuse Through MembraneCytosolic Receptor
Receptor Binding Inside Cell
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Hormones and Signal Transduction• Binding to Receptor
Steroid Hormones Diffuse Through MembraneCytosolic Receptor
Receptor Binding Inside Cell
Non-steroid Hormone
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Hormones and Signal Transduction• Binding to Receptor
Steroid Hormones Diffuse Through MembraneCytosolic Receptor
Receptor Binding Outside of Cell
Receptor Binding Inside Cell
Non-steroid Hormone
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Hormones and Signal Transduction• Binding to Receptor
Steroid Hormones Diffuse Through MembraneCytosolic Receptor
Receptor Binding Outside of Cell
Numerous Internal Message Carriers
Receptor Binding Inside Cell
Non-steroid Hormone
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Hormones and Signal Transduction• Receptors
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Hormones and Signal Transduction• Receptors
Interaction of Hormone with Receptor Changes Receptor
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Hormones and Signal Transduction• Receptors
Interaction of Hormone with Receptor Changes ReceptorReceptor Change Alters Interactions with Other Proteins
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Hormones and Signal Transduction• Receptors
Interaction of Hormone with Receptor Changes ReceptorReceptor Change Alters Interactions with Other Proteins
Changes on Hormone Binding
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Hormones and Signal Transduction• Membrane-bound Receptors
G-Protein Coupled Receptor
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Hormones and Signal TransductionG-protein Coupled Receptors (GPCRs)
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Hormones and Signal TransductionG-protein Coupled Receptors (GPCRs)
Almost 800 Genes in Human Genome
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Hormones and Signal TransductionG-protein Coupled Receptors (GPCRs)
Almost 800 Genes in Human Genome460 Olfactory
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Hormones and Signal TransductionG-protein Coupled Receptors (GPCRs)
Almost 800 Genes in Human Genome460 Olfactoryβ-adrenergic Receptor
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Hormones and Signal TransductionG-protein Coupled Receptors (GPCRs)
Almost 800 Genes in Human Genome460 Olfactoryβ-adrenergic Receptor
Membrane Bound
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Hormones and Signal TransductionG-protein Coupled Receptors (GPCRs)
Almost 800 Genes in Human Genome460 Olfactoryβ-adrenergic Receptor
Membrane BoundSeven Transmembrane
Domains
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Hormones and Signal TransductionG-protein Coupled Receptors (GPCRs)
Almost 800 Genes in Human Genome460 Olfactoryβ-adrenergic Receptor
Membrane BoundSeven Transmembrane
Domains
Extracellular Domain
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Hormones and Signal TransductionG-protein Coupled Receptors (GPCRs)
Almost 800 Genes in Human Genome460 Olfactoryβ-adrenergic Receptor
Membrane BoundSeven Transmembrane
Domains
Extracellular Domain
Intracellular Domain
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GPCR Action Cycle
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GPCR Action Cycle
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Hormone
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Binding of Hormone
Hormone
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Binding of Hormone
Hormone Structural Change of Receptor
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Binding of Hormone
Hormone Structural Change of Receptor
Replacement of GDP by GTP
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Binding of Hormone
Hormone Structural Change of Receptor
Replacement of GDP by GTPActivation of an Enzyme
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Binding of Hormone
Hormone Structural Change of Receptor
Replacement of GDP by GTPActivation of an Enzyme
Return to Original
State
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Hormones and Signal Transduction• Receipt of Message
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Hormones and Signal Transduction• Receipt of Message
Membrane Receptor Proteins Internalize Message
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Hormones and Signal Transduction• Receipt of Message
Membrane Receptor Proteins Internalize MessageActivate Synthesis of Second Messengers
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Hormones and Signal Transduction• Receipt of Message
Membrane Receptor Proteins Internalize MessageActivate Synthesis of Second Messengers
Inositol 1,4,5 Trisphosphate (IP3)
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Hormones and Signal Transduction• Receipt of Message
Membrane Receptor Proteins Internalize MessageActivate Synthesis of Second Messengers
Inositol 1,4,5 Trisphosphate (IP3)
Cyclic AMP (cAMP)
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Hormones and Signal Transduction• Receipt of Message
Membrane Receptor Proteins Internalize MessageActivate Synthesis of Second Messengers
Inositol 1,4,5 Trisphosphate (IP3)
Cyclic AMP (cAMP)
Ca++
Ca++
Ca++Ca++
Ca++
Ca++
Calcium Ions
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Hormones and Signal Transduction• Receipt of Message
Membrane Receptor Proteins Internalize MessageActivate Synthesis of Second Messengers
Inositol 1,4,5 Trisphosphate (IP3)
Cyclic AMP (cAMP)Cyclic GMP (cGMP)
Ca++
Ca++
Ca++Ca++
Ca++
Ca++
Calcium Ions
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Hormones and Signal Transduction• Receipt of Message
Membrane Receptor Proteins Internalize MessageActivate Synthesis of Second MessengersCovalent Modification of “Downstream” Proteins
Inositol 1,4,5 Trisphosphate (IP3)
Cyclic AMP (cAMP)Cyclic GMP (cGMP)
Ca++
Ca++
Ca++Ca++
Ca++
Ca++
Calcium Ions
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Hormones and Signal Transduction• Receipt of Message
Membrane Receptor Proteins Internalize MessageActivate Synthesis of Second MessengersCovalent Modification of “Downstream” ProteinsAlteration of Gene Expression
Inositol 1,4,5 Trisphosphate (IP3)
Cyclic AMP (cAMP)Cyclic GMP (cGMP)
Ca++
Ca++
Ca++Ca++
Ca++
Ca++
Calcium Ions
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Hormones and Signal Transduction• Receipt of Message
Membrane Receptor Proteins Internalize MessageActivate Synthesis of Second MessengersCovalent Modification of “Downstream” ProteinsAlteration of Gene ExpressionChange of Enzyme Activities
Inositol 1,4,5 Trisphosphate (IP3)
Cyclic AMP (cAMP)Cyclic GMP (cGMP)
Ca++
Ca++
Ca++Ca++
Ca++
Ca++
Calcium Ions
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Hormones and Signal Transduction• GPCRs and G-Proteins
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Hormones and Signal Transduction• GPCRs and G-Proteins
βγ
GPCR
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Hormones and Signal Transduction• GPCRs and G-Proteins
βγ
GPCR
Resting State
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Hormones and Signal Transduction• GPCRs and G-Proteins
G-Proteins Bind Guanine Nucleotides (GDP and GTP)
βγ
GPCR
Resting State
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Hormones and Signal Transduction• GPCRs and G-Proteins
G-Proteins Bind Guanine Nucleotides (GDP and GTP)Heterotrimeric - α,β,γ Subunits
βγ
GPCR
Resting State
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Hormones and Signal Transduction• GPCRs and G-Proteins
G-Proteins Bind Guanine Nucleotides (GDP and GTP)Heterotrimeric - α,β,γ SubunitsAssociate with GPCRs
βγ
GPCR
Resting State
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Hormones and Signal Transduction• GPCRs and G-Proteins
G-Proteins Bind Guanine Nucleotides (GDP and GTP)Heterotrimeric - α,β,γ SubunitsAssociate with GPCRsAltered by GPCR’s Binding of Hormone
βγ
GPCR
Resting State
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Hormones and Signal Transduction• GPCRs and G-Proteins
G-Proteins Bind Guanine Nucleotides (GDP and GTP)Heterotrimeric - α,β,γ SubunitsAssociate with GPCRsAltered by GPCR’s Binding of Hormone
βγ
GPCR
Resting State
Epinephrine
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Hormones and Signal Transduction• GPCRs and G-Proteins
G-Proteins Bind Guanine Nucleotides (GDP and GTP)Heterotrimeric - α,β,γ SubunitsAssociate with GPCRsAltered by GPCR’s Binding of Hormone
βγ
GPCR
Resting State
βγ
GPCREpinephrine
Epinephrine
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Hormones and Signal Transduction• GPCRs and G-Proteins
G-Proteins Bind Guanine Nucleotides (GDP and GTP)Heterotrimeric - α,β,γ SubunitsAssociate with GPCRsAltered by GPCR’s Binding of Hormone
βγ
GPCR
GTP GDPResting State
βγ
GPCREpinephrine
Epinephrine
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Hormones and Signal Transduction• GPCRs and G-Proteins
G-Proteins Bind Guanine Nucleotides (GDP and GTP)Heterotrimeric - α,β,γ SubunitsAssociate with GPCRsAltered by GPCR’s Binding of Hormone
βγ
GPCR
GTP GDPResting State
βγ
GPCREpinephrine
Epinephrine
+
βγ
GPCR
Active
Epinephrine
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Hormones and Signal Transductionβ-adrenergic Receptor Signaling
Creation of the Second Messenger
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Hormones and Signal Transductionβ-adrenergic Receptor Signaling
Creation of the Second Messenger
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Hormones and Signal Transductionβ-adrenergic Receptor Signaling
Creation of the Second Messenger
Adenylate Cyclase
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Hormones and Signal Transductionβ-adrenergic Receptor Signaling
Also Membrane Bound
Creation of the Second Messenger
Adenylate Cyclase
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Hormones and Signal Transductionβ-adrenergic Receptor Signaling
Also Membrane Bound
Adenylate Cyclase
Creation of the Second Messenger
Adenylate Cyclase
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Hormones and Signal Transductionβ-adrenergic Receptor Signaling
Activated by binding to α-subunit of G-protein
Also Membrane Bound
Adenylate Cyclase
Creation of the Second Messenger
Adenylate Cyclase
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Hormones and Signal Transductionβ-adrenergic Receptor Signaling
ATP
cAMP + PPi
Activated by binding to α-subunit of G-protein
Also Membrane Bound
Adenylate Cyclase
Creation of the Second Messenger
Adenylate Cyclase
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Hormones and Signal Transductionβ-adrenergic Receptor Signaling
ATP
cAMP + PPi
Activated by binding to α-subunit of G-protein
Second Messenger
Also Membrane Bound
Adenylate Cyclase
Creation of the Second Messenger
Adenylate Cyclase
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Hormones and Signal Transductionβ-adrenergic Receptor Signaling
ATP
cAMP + PPi
Activated by binding to α-subunit of G-protein
Second Messenger
Also Membrane Bound
Adenylate Cyclase
Transmits Signal
Creation of the Second Messenger
Adenylate Cyclase
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Hormones and Signal Transduction• Actions of the Second Messenger
4 cAMP
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Hormones and Signal Transduction• Actions of the Second Messenger
Protein Kinase A
4 cAMP
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Hormones and Signal Transduction• Actions of the Second Messenger
Protein Kinase A
(Inactive)
4 cAMP
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Hormones and Signal Transduction• Actions of the Second Messenger
Protein Kinase A
(Inactive)
4 cAMP
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Hormones and Signal Transduction• Actions of the Second Messenger
Protein Kinase A
(Inactive)
4 cAMP
Catalytic Subunits
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Hormones and Signal Transduction• Actions of the Second Messenger
Protein Kinase A
(Inactive)
4 cAMP
Regulatory SubunitsCatalytic Subunits
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Hormones and Signal Transduction• Actions of the Second Messenger
Protein Kinase A
(Inactive)
4 cAMP Activated
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Hormones and Signal Transduction• Actions of the Second Messenger
Protein Kinase A
(Inactive)
4 cAMP Activated
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Hormones and Signal Transduction• Actions of the Second Messenger
Protein Kinase A
(Inactive)
4 cAMP Activated
Activity Altered
by Phosphorylation
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Metabolic Melody
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Metabolic Melody
The Tao of Hormones(To the tune of "The Sound of Silence")
Copyright © Kevin Ahern
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The Tao of Hormones(To the tune of "The Sound of Silence")
Copyright © Kevin Ahern
Biochemistry my friendIt's time to study you again
Mechanisms that I need to knowAre the things that really stress me so
"Get these pathways planted firmly in your head,"Ahern said
Let's start with ep-inephrineMembrane proteins are well knownChanged on binding this hormoneRearranging selves without protest
Stimulating a G alpha STo go open up and displace its GDP
With GTPBecause of ep-inephrine
Active G then moves a ways Stimulating ad cyclase
So a bunch of cyclic AMP Binds to kinase and then sets it free
All the active sites of the kinases await Triphosphate
Because of ep-inephrine
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The Tao of Hormones(To the tune of "The Sound of Silence")
Copyright © Kevin Ahern
Biochemistry my friendIt's time to study you again
Mechanisms that I need to knowAre the things that really stress me so
"Get these pathways planted firmly in your head,"Ahern said
Let's start with ep-inephrineMembrane proteins are well knownChanged on binding this hormoneRearranging selves without protest
Stimulating a G alpha STo go open up and displace its GDP
With GTPBecause of ep-inephrine
Active G then moves a ways Stimulating ad cyclase
So a bunch of cyclic AMP Binds to kinase and then sets it free
All the active sites of the kinases await Triphosphate
Because of ep-inephrine
Muscles are affected then Breaking down their glycogen So they get a wad of energy In the form of lots of G-1-P
And the synthases that could make a glucose chain All refrain
Because of ep-inephrineNow I've reached the pathway end
Going from adrenalin Here's a trick I learned to get it right Linking memory to flight or fright
So the mechanism that's the source of anxious fears Reappears
When I make ep-inephrine