Download Olfactory Signalling - Biochemistry at CSU, Stanislaus

Alexander Skochko
Chris Gilbertson

Reveals Important Features of one’s surroundings
◦ Is it poisonous here?
◦ Have things died here?
◦ Is this food?


The absence of the sense of smell is called
“Anosmia.”
An overly acute sense of smell is known as
‘hypernosmia.’
◦ If you or somebody you know is a hypernosmiac please
contact NASA, as their hypernosmiac is getting old – and
the job is essential to long missions.
1.
A volatile molecule
from outside of the
body, called an
odorant, binds to
either:
a) A protein that
transfers the odorant
to the receptor.
b) Directly to the
receptor.
2.
The odorant’s
ligation with the
receptor
activates the
receptor site,
which catalyzes
the replacement
of GDP on the
alpha subunit of
a G protein with
GTP.

The enzymatic receptors activated by
the binding of odorant molecules have
low specificity for the odorants.
◦ This allows increased diversity of smells
that can activate the receptor neurons in
the nose.
◦ When two substances smell similar to each
other, it is likely that the molecules
responsible are similar in nature to each
other.

Since each receptor has the ability to signal
for multiple kinds of odorant, olfaction is a
burgeoning field of research. There have not
been many odorant-receptor ligands
identified in the literature.1
◦ Identifying odorant-receptor ligands would not
provide much insight into the process of olfaction,
as the rest of the process would be the same as
other ligands. The receptor changes shape in
response to the ligation, and the change in shape
results in the activation of the catalytic character of
the receptor.
3. The GTP binding
now causes the
alpha subunit to
disassociate
from the rest of
the G protein,
and to
subsequently
associate with
adenylyl cyclase.
4. The G protein
binding with
adenylyl cyclase
activates the
enzyme,
catalyzing the
production of
cyclic adenosine
monophosphate.
5. The cAMP
increase causes
calcium ion
channels to
open, raising the
concentration of
Ca2+ in the
olfactory cell
6.The increased calcium ion
concentration causes another gated
ion channel to open, this time
allowing the release of chloride from
the cell.
a. The net intake of calcium ions
and output of chloride ions causes
an increased membrane potential in
the receptor cell. If the potential
reaches a certain magnitude, the
neuron on which the charge is
building will send a signal to the
brain. This signal is part of what is
perceived as a smell.


There is no known route by which olfactory
recognition enzymes are deactivated by
another olfactory recognition enzyme.
Smells are recognized as a variety of
signals.2,3
◦ Some odorants have high affinity for some
of the Golf receptors, and low affinity for
other Golf sites.
 The combination of signals from high affinity and low affinity
sites is what is recognized by the brain as a particular scent.
 This reliance upon similarity between recognized odorants
can have negative results. For examples: cyanide smells of
almonds, and phosgene gas smells of liquorish – but one
should not inhale either.
1.
2.
3.
Phosphodiesterases
convert the cyclic
adenosine
monophosphate back to
AMP, shutting down the
calcium ion channels.
The G protein converts
the GTP back to GDP by
hydrolysis, causing
association of the alpha
subunit with the rest of
the protein.
The receptor protein is
then phosphorylated by
a kinase, causing
temporary inactivation,
or ‘Nose Blindness.’
1. Bush, C. , Jones, S. , Lyle, A. , Minneman, K. , Ressler, K. , et al. (2007).
Specificity of olfactory receptor interactions with other g protein-coupled
receptors. Journal of Biological Chemistry, 282(26), 19042-19051.
2. Bettina Malnic, Junzo Hirono, Takaaki Sato, Linda B Buck, Combinatorial
Receptor Codes for Odors, Cell, Volume 96, Issue 5, 5 March 1999, Pages
713-723, ISSN 0092-8674, http://dx.doi.org/10.1016/S0092-8674(00)80581-4.
(http://www.sciencedirect.com/science/article/pii/S0092867400805814)
3. Rokni, Dan, Vivian Hemmelder, Vikrant Kapoor, and Venkatesh N Murthy.
"An Olfactory Cocktail Party: Figure-ground Segregation of Odorants in
Rodents." Nature Neuroscience, 17.9 (2014): 1225-1232. doi: 10.1038/nn.3775
4. Nelson, David. Lehninger Principles of Biochemistry. 5th ed. New
York, NY: Sara Tenny, 2008. Page 466.