Signal transduction -Insulin, glucagon and glucose regulation Flashcards
Describe how the binding of IRS-1 to phosphorylated Tyr residues in the cytoplasmic domain of
the insulin receptor causes muscle cells to transport glucose from the bloodstream into the cells.
After IRS-1 binds to the phosphotyrosine residues of the insulin receptor, it is phosphorylated by the
cytoplasmic domain of the receptor. The enzyme PI3K binds to the phosphotyrosine residues on IRS-1, which
activates it. Activated PI3K phosphorylates PIP2 lipid molecules in the plasma membrane to form PIP3. The
protein kinase PDK1 binds to the PIP3 lipids in the membrane. This activates PDK1, allowing it to phosphorylate
and activate PKB. By an unknown mechanism, activated PKB triggers the fusion of vesicles containing the
glucose transporter GLUT4 to the plasma membrane of the muscle cell. Because it is now present on the
muscle cell surface, GLUT4 can transport glucose from the blood circulation into the muscle cell, which causes
blood glucose concentration to decrease.
In addition to the transport of glucose into muscle cells, insulin also stimulates the glucose to be
polymerized into glycogen. Which key enzyme is activated to perform the latter function?
Glycogen synthase
The brain and neurons of the central nervous system critically rely on glucose in the blood
circulation to provide them with a constant source of energy (ATP) to keep functioning. Thus, when
the blood glucose concentration drops, the pancreas immediately responds to correct the situation.
Describe how it achieves this.
The pancreas releases glucagon, which binds to the glucagon receptor on liver cells. The glucagon receptor
is a GPCR that activates PKA. PKA phosphorylates and activates glycogen phosphorylase kinase (GPK) which in
turn phosphorylates and activates glycogen phosphorylase. The latter enzyme breaks down the glycogen that
is stored in liver cells to glucose, which is released into the bloodstream to restore normal blood glucose
concentration
By describing neural signal transduction (the formation of an action potential), explain why
neurons require so much energy (ATP) to keep functioning.
An action potential is caused by the opening of voltage gated Na+
channels in the membranes of neurons.
This causes membrane depolarisation due to the movement of Na+
ions into the neuron. Membrane
repolarisation is subsequently achieved by the closing of the Na+
channels and the opening of voltage gated K+
channels, allowing the movement of K+
from the cytoplasm of the neuron to the external environment. The K+
channel then closes. In order to generate another nerve impulse (action potential), the neuron has to reestablish the normal concentrations of Na+ and K+
inside and outside the cell (the recovery phase of the action
potential). This is achieved by the Na+
/K+ ATPase, which uses the energy obtained from ATP hydrolysis to pump
Na+ back out of the cell into the external environment and K+
into the cell from the external environment. It is
because of the ATP used by this transporter that neurons require so much energy (supplied by blood glucose)
to keep functioning.
An action potential (nerve impulse) is transmitted from one neuron to the next by the release of
neurotransmitters into the synaptic cleft. How are the neurotransmitters subsequently removed?
In two ways: the neurotransmitters are either transported across the membrane back into the presynaptic
neuron (re-uptake), or are degraded by enzymes in the synaptic cleft
How does the release of neurotransmitters by neurons trigger muscle contraction? (you don’t
have to describe the process of muscle contraction, only what triggers it).
The neurons release the neurotransmitter acetylcholine which binds to acetylcholine receptors in the
muscle cell plasma membrane. These receptors are ligand gated Na+
channels – when acetylcholine binds to
them, they open and cause Na+
to rush into the muscle cells from the external environment. This depolarises
the muscle cell membrane and causes voltage gated L-type Ca2+ channels in the muscle cell membrane to
open. Ca2+ enters the muscle cell through these channels and the rise in Ca2+ concentration in the muscle cell
cytoplasm triggers muscle cell contraction
Neurons require a lot of energy to function, but most of the ATP used in the body is used by
muscle cells. By referring to the mechanism of muscle cell contraction and the role of Ca2+ in this
process, explain why this is the case.
Entry of Ca2+ into muscle cells from the external environment and the sarcoplasmic reticulum triggers
muscle contraction by the binding of the Ca2+ to troponin. This causes the troponin to shift position and expose
the myosin binding site on actin filaments. The myosin head domain hydrolyses its bound ATP to ADP and
phosphate and binds to the exposed binding site on the actin filament. Release of the ADP and phosphate
causes the myosin to change shape and slide the actin filament past it. The myosin is released from the actin
when it binds to ATP again and the cycle repeats as the muscle cell keeps contracting. For muscle cell
contraction to stop and the muscle to relax, the Ca2+ has to be removed from the muscle cell cytoplasm. This is
achieved by SERCA that uses the energy obtained by hydrolysing ATP to pump Ca2+ back into the sarcoplasmic
reticulum (ER) (though less important, the plasma membrane Ca2+ ATPase also contributes by pumping Ca2+ to
the outside of the cell). From this description, one can see that myosin uses ATP to move the actin filaments
during contraction, while SERCA uses ATP to allow muscle relaxation, thus explaining why muscle cells require
so much energy.
Explain why adrenalin increases the i) strength and ii) rate of heart muscle contraction
The β1 adrenergic receptor that is situated on heart muscle cells is a GPCR that activates PKA after binding
to adrenalin. i) PKA phosphorylates the L-type Ca2+ channels, causing more Ca2+ to enter the heart muscle cells
from the external environment when the muscle cell membranes depolarise. It also phosphorylates the
ryanodine receptors (Ca2+
channels) in the sarcoplasmic reticulum, causing more Ca2+ to be released into the
cytoplasm from the sarcoplasmic reticulum. The higher cytoplasmic Ca2+ concentration caused by these two
mechanisms increases the strength of muscle cell contraction. ii) PKA phosphorylates phospholamban, a
protein that normally binds to SERCA and inhibits its function. This causes phospholamban to be released from
SERCA, increasing the rate at which SERCA pumps Ca2+ from the cytoplasm back into the sarcoplasmic
reticulum and thus the rate at which the heart muscle cell can contract.
PKA activated by adrenergic receptors stimulate muscle contraction in heart muscle cells, but
has to opposite effect in smooth muscle cells. Explain.
In smooth muscle cells, myosin needs to be phosphorylated by MLCK to bind to actin and cause muscle cell
contraction. PKA phosphorylates MLCK and inhibits its function. In addition, PKA phosphorylates MLC
phosphatase, which then dephosphorylates any existing phosphorylated myosin. In this way, myosin is
prevented from being phosphorylated and from binding to actin, thus causing smooth muscle cell relaxation.
i) Which class of protease enzymes are activated in apoptosis? ii) How do they kill cells
) i) caspases. ii) executioner caspases have two functions. Firstly, they digest proteins that normally inhibit
DNase I. DNase I therefore becomes active and digests all the DNA in the cell into short fragments (the cell
therefore can’t make any more proteins). Secondly, they digest the actin filaments in the cell and destroy the
cell cytoskeleton. This causes the cell to lose its shape and detach from any other cells and surrounding
proteins (extracellular matrix) it might have been bound to. The cell then undergoes blebbing – it breaks up
into smaller pieces, or membrane-bound vesicles. The vesicles are taken up and destroyed by phagocytic cells
(macrophages) and the cell eventually disappears.
glucose is converted into what in Adipose cells
fatty acids
What stimulates the triglyceride synthesis in adipose cells ?
PKB
What are the four steps the enable action potential ,name them.
Rest
depolarization
re-polarization
recovery
As during synaptic transmission, depolarization of the
neuron membrane causes Ca2+
to enter the neuron,
which triggers the release of a neurotransmitter called
Acetylcholine
