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Have you ever had a sudden fright?
Perceived a threat, you’re all geared up for fight or flight
Heart pounding, face flushed, hair standing up on end.
It’s partly from a hormone called epinephrine
Epinephrine’s got another name: adrenaline
Secreted from adrenal glands, it’s the stuff in EpiPens
A shot can save your life, if you have an allergy
Involving sensitivity to nuts or stings from bees.
Epinephrine’s polar so it can’t diffuse
Through the lipid bilayer, so instead it induces
A second messenger, it’s cyclic AMP
Which stimulates massive cellular activity.
Let’s learn how liver cells react to an epinephrine dose.
What they do is break down glycogen to glucose.
Which streams into your blood to give you energy,
Required to respond to threats | as you fight or flee.
How does epinephrine get your liver cells to do this function?
It’s three steps, first reception then transduction,
Then cellular response, an enzyme activation.
We’re learning ‘bout the process of cell communication.
CHORUS
Cell communication:
Works through phases three,
Reception of the ligand
They’re complementary,
(TWO)
Second messenger released
Transduction is a beast!
Now amplified response until the stimulus has ceased!
Today’s focus is G protein coupled receptors.
We’ll leave the other systems, for another lecture.
Epinephrine’s the ligand that with the receptor binds.
It’s a hormone — the hydrophilic kind.
Ligands bind to receptors only if their shape matches.
It’s specific based on complementary attachment
Epinephrine goes everywhere but only affects,
Cells with receptors with which it can connect
Once epinephrine binds at the the receptor binding site
The receptor changes shape on its cytoplasmic side
Where, just inside the membrane, you’ll find the G protein.
Which until epinephrine binds is dormant asleep
In its dormant form the G protein’s bound to GDP,
But epinephrine binding makes it bind with GTP
Then the G protein drifts in the membrane space
’Til it bumps into Adenylyl cyclase
A membrane-bound enzyme whose signaling function’s
Activating a second messenger setting up transduction.
Transduction converts a message into another kind.
Message 1 was the ligand, which came along to bind
With the receptor which in response woke up the G protein
Which gets adenylyl cyclase to take an ATP
And remove two phosphates making cyclic AMP
That’s the second messenger, it takes the message deep
Into the cytoplasm where it unleashes a chain of
Enzyme action: a phosphorylation cascade.
The message was received, it was then transduced
Next we’ll see how the cellular response gets produced
CHORUS
A phosphorylation cascade involves a chain
Of enzymes | known as kinases
These kinases | get phosphorylated
Which means “gaining a phosphate” which activates them
And what do kinases do when they’re charged up with a phosphate?
They find the chain’s next kinase and phosphorylate it.
This chain of activation is like falling dominoes,
‘Cause that’s how a phosphorylation cascade goes.
And each kinase carries out multiple activations,
Causing massive signal amplification
The signal grows in strength | with every kinase action,
Building in intensity a chain reaction
One epinephrine binds causing many cyclic AMPs
Each of which activates many kinase proteins,
By the chain’s last kinase: tens of thousands activated,
A cellular tsunami as the chain is terminated.
Glycogen phosphorylase is the enzyme at the end.
It makes glucose by hydrolyzing glycogen.
So into the blood from the liver, glucose gets secreted,
And the threat that started this story can be fled from or defeated.
It’s adaptive how your cells are poised to spring into action
Once they hear epinephrine’s alarm there’s a reaction,
In all eukaryotes from amoebas to acacias.
G protein coupled receptors used in cell communication!
CHORUS
Back to the ligand at the receptor it only stays
For a moment before it diffuses away
So when the threat is gone, the cascade gets shut down
With no adrenal secretion, the receptor’s unbound.
G protein drops the phosphate, now bound to GDP
It goes back to sleep, and stops its activity
Bound to GDP it no longer stimulates
Adenylyl cyclase, which no longer creates
Cyclic AMP so the second message stops,
Kinase phosphorylation quickly drops.
As other enzymes, protein phosphatases,
Clip off phosphates, and turn off kinases
Glycogen phosphorylase stops hydrolyzing
Glycogen so blood glucose normalizes
Liver cells return to their resting state.
I love how G proteins let cells communicate!
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