Ligands & Receptors Quiz.text - - 6/8/99

QUESTION 1:  What is a "binding site" on a protein?  What sort of
structure is it? ANSWER:  A binding site is a part of a protein which
has a shape and distribution of charge which enables it to bind another
(usually smaller) molecule which has a complementary shape and charge. 
Just as a lock fits a key.

QUESTION 2:  What is a receptor? ANSWER:  A receptor is a binding site
on a protein,  involved in cell to cell communication.  It is usually on
the surface of a cell.  Not all binding sites are receptors ‹ some are
active sites of enzymes, not involved in cell communication.

QUESTION 3:  What is a ligand? ANSWER:  A ligand is a molecule which
attaches to a binding site on another molecule.

QUESTION 4:  What is the difference between a ligand and a chemical
messenger? ANSWER:  All chemical messengers are ligands, but not all
ligands are chemical messengers.

QUESTION 5:  What is allosteric modulation of a protein? ANSWER: 
Proteins can adopt different shapes depending on factors such as pH,
surrounding electrical fields, or binding of ligands.  This is
allosteric modulation.

QUESTION 6:  How is allosteric modulation of a protein different from
covalent modulation? ANSWER:  Covalent modulation involves the formation
of a "covalent" bond between the protein and another chemical component,
such a phosphate group.  Allosteric modulation does not require a proper
bond to be formed, but can occur as a result of a relatively loose
binding of a ligand due to electrostatic attraction.

QUESTION 7:  What is a membrane channel made up of? ANSWER:  A typical
membrane channel is made up of a number of protein subunits, each
roughly cylindrical in shape.  Groups of 4, 5, or 6 such subunits are
joined lengthwise, forming a narrow passage in their middle.

QUESTION 8:  What are membrane channels good for? ANSWER:  Membrane
channels are needed to allow polar (charged) molecules to pass through a
cell membrane.  The movement of these molecules can also be regulated 
by modulation of the channel proteins. This simple mechanism has a lot
of extrememly useful applications (action potentials, synaptic
transmission, hormone actions etc.)

QUESTION 9:  What's the difference between a membrane channel and a
pump? ANSWER:  A channel is just a hole.  Some are always open, others
alternate between open and closed states.  Movement through a channel
depends on diffusion down an electrochemical gradient.  A pump actively
transports substances, often against electrochemical gradients.  Like a
channel, it is made of protein, but a pump is more complicated with more
moving parts.

QUESTION 10:  What makes the gates in a membrane channel swing? ANSWER: 
It's basically a special case of modulation of a protein, where the bit
that changes its shape happens to block the channel.  Gates can be
ligand-sensitive, voltage-sensitive or mechano-sensitive.  Some channels
have both ligand-sensitive and voltage-sensitive gates.

QUESTION 11:  What sorts of channels are involved in synaptic
transmission? ANSWER:  Voltage-sensitive calcium channels trigger the
release of transmitter from the nerve ending. The transmitter then binds
to ligand-sensitive channels on the postsynaptic membrane.  Or the
transmitter may bind to a receptor which indirectly controls a separate
channel nearby .

QUESTION 12:  Does all cell to cell communication work through membrane
channels?  What if the chemical messenger is highly lipid soluble?
ANSWER:  No, cell surface receptors may be proteins that are not part of
a channel.  Activation of such a receptor may just turn on intracellular
enzyme systems.  For lipid-insoluble messengers, the receptor protein
acts as a "bridge" between the outside world and the intracellular
compartment.  However, if the chemical messenger is lipid-soluble, there
is no need for a surface receptor.  Lipid-soluble messengers can pass
straight through the cell membrane ‹ they bind to intracellular
receptors (eg. in the cell nucleus where they can influence protein
synthesis).

QUESTION 13:  What's the difference between a G-protein and a G-string?
ANSWER:  I'm working on this one... If you think of a funny punch-line,
let me know.

QUESTION 14:  What is a G-protein?  Why G? ANSWER:  G-proteins are
special proteins which are attached to certain cell surface receptors. 
They act as a link between the receptor and a channel or an
intracellular enzyme system.  They are "G" because, in their inactive
state,  they bind a molecule called guanosine di-phosphate (GDP).

QUESTION 15:  What does a G-protein do? ANSWER:  When the receptor
associated with a G-protein is activated, the G-protein swaps the GDP
(guanosine diphosphate) that is bound to it for GTP (guanosine
triphosphate).  This causes the G-protein to become activated.  The
G-protein then does useful things by turning on other intracellular
enzyme systems or modulating membrane channels.

QUESTION 16:  What's the difference between a hormone and a
neurotransmitter? ANSWER:  Both are chemical messengers and they can
even be the same chemical.  What makes them different is that a hormone
acts through the bloodstream and contacts almost all cells in the body,
whereas the neurotransmitter is dropped right onto a cell and doesn't
spread very far from it.

QUESTION 17:  What is a second messenger? ANSWER:  A second messenger is
a chemical agent which is released or accumulated inside the cell as a
result of the interaction of the extracellular (first) chemical
messenger with its receptor.  The second messenger (eg. cyclic AMP,
calcium ion) diffuses within the cell, turning enzymes on here and there
(and maybe turning some enzymes off).

QUESTION 18:  Some receptors are linked to an intracellular enzyme
called tyrosine kinase.  What is their special role in life? ANSWER: 
Tyrosine-kinase linked receptors mediate the actions of various growth
factors, agents which stimulate cell division and hormones which control
cell metabolism (eg. insulin).

QUESTION 19:  How can a hormone be selective in its actions when it
contacts almost every cell in the body? ANSWER:  Only cells with the
right receptor can respond to the hormone.

QUESTION 20:  What is the difference between a hormone and a paracrine
agent? ANSWER:  A paracrine agent acts on cells close to the source of
release of the paracrine agent, via the extracellular fluid.  However,
if it enters the bloodstream and acts on other cells at a distance, it
may also  be a hormone...

QUESTION 21:  What makes a membrane ion channel selective about the ions
that can get through it? ANSWER:  A narrow part of the channel known as
a selectivity filter.  This selects ions according to their size and
charge.  Fixed charges lining the entrance to the filter are thought to
select ions according to whether they are positive or negative.  Narrow
channels obviously allow only small ions through.  However, some
channels magically allow some large ions (eg. potassium) through  more
easily than smaller ones (eg. sodium).

QUESTION 22:  How does a receptor antagonist work? ANSWER:  An
antagonist binds to the receptor and prevents the normal ligand
(agonist) from binding to it.  In order to bind to the receptor, the
antagonist must be partly similar in shape to the agonist.

QUESTION 23:  If an antagonist binds to a receptor,  why does it not
also activate the receptor? ANSWER:  An antagonist must be similar in
shape to the normal ligand in order to bind specifically to the
receptor. However, it must lack a critical component, normally necessary
to activate the receptor and modulate the receptor protein. Antagonists
are not perfect and may activate the receptor to some extent.

QUESTION 24:  Once an antagonist binds to a receptor, how can it be
removed? ANSWER:  Some antagonists are competitive.  This means that
they compete with the normal ligand for the receptor site.  Winning
depends on strength of numbers (concentration) and  strength of
attraction to the binding site (affinity).  Some antagonists are
non-competitive ‹ they stick to the binding site like glue and fully
saturate it‹ a good place to find them is in natural products like
spider venom.

QUESTION 25:  What is the difference between "modulation" of a receptor
protein and "up-regulation" or "down-regulation" of a receptor? ANSWER: 
Modulation involves inducing a change in the shape of a receptor and
activating it.  Up-regulation involves actually manufacturing more
receptors and putting them in place.  Down-regulation involves allowing
the receptor numbers to decrease by natural attrition (receptors are
continually recycled).

QUESTION 26:  Why do heroin addicts tend to increase the dose they take?
ANSWER:  Chronic use of heroin causes down-regulation of the receptors
which bind the heroin (these receptors normally respond to the body's
own "endogenous opiates".  This means you have to increase the dose to
get the same effect.

QUESTION 27:  A drug called "naloxone" is a competitive antagonist for
the opiate receptor.  When might this drug be useful? ANSWER:  In
treating heroin or morphine overdose. A related drug Naltrexone, which
has a longer duration of action, is used as a treatment for opiate
addiction.  It apparently stops the user from experiencing the "high" of
a heroin "hit" ‹ so they tend not to bother.

QUESTION 28:  Under what physiological circumstances might receptors be
up-regulated? ANSWER:  When there is reduced supply of the natural
ligand.  This occurs in disease states such as failure of an endocrine
gland or degeneration of a neural pathway.  Up-regulation results in
supersensitivity of the target cells, which helps to compensate for a
low concentration of ligand.