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OLFACTIONOLFACTION
SARAMITA DESARAMITA DE
CHAKRAVARTICHAKRAVARTI
Research AssistantResearch Assistant
Chembiotech Research LaboratoriesChembiotech Research Laboratories
Worcestershire, United KingdomWorcestershire, United Kingdom
What is Olfaction ?What is Olfaction ?
Olfaction (the sense of smell i.e., the detection ofOlfaction (the sense of smell i.e., the detection of
small molecules in the air ) is one of the mostsmall molecules in the air ) is one of the most
ancient sense, which allows vertebrates andancient sense, which allows vertebrates and
other organisms with olfactory receptors toother organisms with olfactory receptors to
identify food, mates, predators and provide bothidentify food, mates, predators and provide both
sensual pleasure (the odour of flowers andsensual pleasure (the odour of flowers and
perfume) as well as warning of danger (spoiledperfume) as well as warning of danger (spoiled
food, chemical dangers).food, chemical dangers).
A Wide Variety of Organic Compounds areA Wide Variety of Organic Compounds are
Detected by OlfactionDetected by Olfaction
Human beings can detect and distinguish thousand of
different compounds by smell, often with considerable
sensitivity and specificity. Most odourants are relatively
small organic compounds with sufficient volatility and they
can be carried as vapours into the nose.
Figure 1 : Structure of different organic molecule
The shape of the molecule rather than itsThe shape of the molecule rather than its
other physical properties is crucialother physical properties is crucial
Figure2 : Structure of different organic molecule
General Physiology of OlfactionGeneral Physiology of Olfaction
 The olfactory region consist of ciliaThe olfactory region consist of cilia
projecting down, out of the olfactoryprojecting down, out of the olfactory
epithelium into a mucous layer.epithelium into a mucous layer.
 The mucous layer is produced byThe mucous layer is produced by
Bowman’s gland, which resides inBowman’s gland, which resides in
the olfactory epithelium.the olfactory epithelium.
 Odorants are volatile chemicalOdorants are volatile chemical
compounds, carried out by inhaledcompounds, carried out by inhaled
air to the Regio olfactoria (Olfactoryair to the Regio olfactoria (Olfactory
epithelium) located in the roof ofepithelium) located in the roof of
the two nasal cavities of the nose.the two nasal cavities of the nose.
 In the olfactory epithelium, olfactoryIn the olfactory epithelium, olfactory
receptor neurons are present. Eachreceptor neurons are present. Each
olfactory receptor neurons have 8-olfactory receptor neurons have 8-
20 whip like ciliary projection.20 whip like ciliary projection.
Figure 3: The Main Nasal Epithelium
 The olfactory receptor neurons extend through the epithelium to contact odorants inThe olfactory receptor neurons extend through the epithelium to contact odorants in
the atmosphere, on the opposite side within the epithelium, the neuronal cells formthe atmosphere, on the opposite side within the epithelium, the neuronal cells form
axons that are bundled in groups of 10-100 to penetrate the ethmoidal cribriformaxons that are bundled in groups of 10-100 to penetrate the ethmoidal cribriform
plate of bone, reaching the olfactory bulb of the brain where they converge toplate of bone, reaching the olfactory bulb of the brain where they converge to
terminate with post-synaptic cells to form synaptic structures called glomeruli. Theterminate with post-synaptic cells to form synaptic structures called glomeruli. The
glomeruli are connected in groups that converge into mitral cells.glomeruli are connected in groups that converge into mitral cells.
 Physiologically, this convergence increases the sensitivity of the olfactory signalPhysiologically, this convergence increases the sensitivity of the olfactory signal
sent to the brain. From the mitral cells the message is sent directly to the highersent to the brain. From the mitral cells the message is sent directly to the higher
levels of the central nervous system in the corticomedial amygdala portion of thelevels of the central nervous system in the corticomedial amygdala portion of the
brain (via the olfactory nerve tract) where the signaling process is decoded andbrain (via the olfactory nerve tract) where the signaling process is decoded and
olfactory interpretation and response occurs.olfactory interpretation and response occurs.
Figure4 : Cells and connection of olfactory epithelium and olfactory bulb
The Trigeminal Sense in theThe Trigeminal Sense in the
Olfactory EpitheliumOlfactory Epithelium
It must also be recognized that the olfactory epithelium contains
another sensory system in the form of "Trigeminal Nerve" receptors,
present in mouth, eyes and nasal cavity.
A number of trigeminal chemical stimulants produce effects
described as hot, cold, tingling or irritating. For examples ---
ChemicalsChemicals
leavo menthol or (-) menthol cold (at moderateleavo menthol or (-) menthol cold (at moderate
concentration)concentration)
hot (at high concentration)hot (at high concentration)
allyl isothiocyanate --- mustard, mustard oilallyl isothiocyanate --- mustard, mustard oil
capciacin --- hot Chile powder, mace spraycapciacin --- hot Chile powder, mace spray
diallyl sulfide --- oniondiallyl sulfide --- onion
The Odorant BindingThe Odorant Binding ProteinsProteins
In 1979, Steven Price & coworkers and later Fesenko. et. al. found a number ofIn 1979, Steven Price & coworkers and later Fesenko. et. al. found a number of
“Odorant Binding Protein” (OBP) for odorant chemicals such as ---“Odorant Binding Protein” (OBP) for odorant chemicals such as ---
5-a-ANDROST-16-EN-3-ONE
Figure 5 : Different odourant binding protein
Function Of OBPFunction Of OBP
 They bind lipophilically to odorants inThey bind lipophilically to odorants in
the aqueous / lipid mucousthe aqueous / lipid mucous
increasing the concentration andincreasing the concentration and
facilitate in transport.facilitate in transport.
 They bind to ligand and receptors &They bind to ligand and receptors &
assist in transport.assist in transport.
 They act as a kind of filter to preventThey act as a kind of filter to prevent
excessive amounts (over stimulation)excessive amounts (over stimulation)
from reaching the receptors.from reaching the receptors.
 The role of OBPs become clear inThe role of OBPs become clear in
2000 with characterization of human2000 with characterization of human
lipocalins involvement in odorantslipocalins involvement in odorants
bindings.bindings.
Figure 6: Partial structure ofFigure 6: Partial structure of
Human OPB IIaHuman OPB IIa
modeled against 1EW3A (CRYSTALmodeled against 1EW3A (CRYSTAL
STRUCTURESTRUCTURE
OF THE MAJOR HORSE ALLERGENOF THE MAJOR HORSE ALLERGEN
EQU C 1)EQU C 1)
Odorant or olfactory receptor (OR)Odorant or olfactory receptor (OR)
 In 1991, Linda Buck andIn 1991, Linda Buck and
Richard Axel discoveredRichard Axel discovered
both the family ofboth the family of
transmembrane proteins,transmembrane proteins,
called odorant receptors.called odorant receptors.
The proteins contained the 7The proteins contained the 7
helical transmembranehelical transmembrane
structure and have sequencestructure and have sequence
similarity to other memberssimilarity to other members
of the G-protein family.of the G-protein family.
 Recently (2000), DoronRecently (2000), Doron
Lancet & co-workers at theLancet & co-workers at the
Weizmann Institute ofWeizmann Institute of
Science Crown HumanScience Crown Human
Genome Center haveGenome Center have
constructed a database ofconstructed a database of
human olfactory receptorhuman olfactory receptor
genes present in differentgenes present in different
chromosomes.chromosomes.
Figure 7 : 7-transmembrane olfactory receptor
Figure 8 : Human olfactory receptor genes by chromosome location
Molecular events in OlfactionMolecular events in Olfaction
 The olfactory stimulus arrives at the sensory cells by diffusion through air.
 The odorant molecule binds directly to an olfactory receptors or to a specific
binding protein that carries the odorant to a receptor.
 Interaction between odorant and the receptor triggers a change in receptor
conformation that result in the replacement of bound GDP by GTP on G-
protein (Golf).
 The activated Golf then activates adenyl cyclase of the ciliary membrane,
which synthesize cAMP from ATP, raising local [cAMP].
 The cAMP gated Na+
and Ca++
channels of the ciliary membrane open and the
influx of Na+ and Ca++
produce a small depolarization called receptor
potential.
 if a sufficient number of odorant molecules encounter receptors, the
receptor potential is strong enough to cause the neuron to fire an action
potential. This relayed to brain in several stages and registers as a specific
smell. These events occur within 100-200 ms.
Figure 9 : Molecular events of Olfaction
Other second messengers inOther second messengers in
olfactionolfaction
 Inositol triphosphate (IPInositol triphosphate (IP33
)actively participate in)actively participate in
olfactory transduction with in certain mammals.olfactory transduction with in certain mammals.
 Recent evidence is that the cAMP is mediated byRecent evidence is that the cAMP is mediated by
another cyclic nucleotide cGMP.another cyclic nucleotide cGMP.
 NO modulate cGMP concentration in mitral cells.NO modulate cGMP concentration in mitral cells.
 Similarly carbon monoxide (CO) serves as aSimilarly carbon monoxide (CO) serves as a
gaseous neuronal messenger linked to cGMPgaseous neuronal messenger linked to cGMP
production.production.
ConclusionConclusion
So from this discussion we can say that olfaction is very important forSo from this discussion we can say that olfaction is very important for
us and also for other animals.us and also for other animals.
Dog’s sense of smell is 1000 times more than humans. People useDog’s sense of smell is 1000 times more than humans. People use
dog’s keen sense of smell in many ways---dog’s keen sense of smell in many ways---
i.i. Govt. agencies use specially trained dogs in search and rescueGovt. agencies use specially trained dogs in search and rescue
missiomissio
ii.ii. Detection of narcotics.Detection of narcotics.
iii.iii. Detection of forensic cadaver material.Detection of forensic cadaver material.
Due to lack of smell the following disorders may be seen---Due to lack of smell the following disorders may be seen---
Anosmia : lack of ability to smellAnosmia : lack of ability to smell
Hyposmia- decreased ability to smellHyposmia- decreased ability to smell
Phantosmia- [“hallucinated smell”] often unpleasant in naturePhantosmia- [“hallucinated smell”] often unpleasant in nature
Dysosmia- things smell differently than they should.Dysosmia- things smell differently than they should.
Hyperosmia- an abnormally acute sense of smellHyperosmia- an abnormally acute sense of smell
Some times olfaction serve as marker for Perkinson’s diseases. SomeSome times olfaction serve as marker for Perkinson’s diseases. Some
illness can be diagnosed by their associated smell( e.g. acetone andillness can be diagnosed by their associated smell( e.g. acetone and
diabetes). So smell therapy and clinical use of odour is an area fordiabetes). So smell therapy and clinical use of odour is an area for
future.future.
AcknowledgementAcknowledgement
 Thanks to Dr. Prof John Kerry, University of London for giving me
constant encouragements and suggestions whenever it is necessary.
 Other Professors and Scholars of my department, to whom I am
indebted for various courtesies.
 The liberal assistance of the non – teaching staffs and technical
assistance of our Technical Assistant of our Department is also
acknowledged.
 I am thankful to my entire colleagues for encouragement and
appreciations and their co – operations.
 Lastly, but not the least, I would like to express my gratitude to my
parents and my sister for their constant encouragements and
blessings on me.
Thank YouThank You

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OLFACTION

  • 1. OLFACTIONOLFACTION SARAMITA DESARAMITA DE CHAKRAVARTICHAKRAVARTI Research AssistantResearch Assistant Chembiotech Research LaboratoriesChembiotech Research Laboratories Worcestershire, United KingdomWorcestershire, United Kingdom
  • 2. What is Olfaction ?What is Olfaction ? Olfaction (the sense of smell i.e., the detection ofOlfaction (the sense of smell i.e., the detection of small molecules in the air ) is one of the mostsmall molecules in the air ) is one of the most ancient sense, which allows vertebrates andancient sense, which allows vertebrates and other organisms with olfactory receptors toother organisms with olfactory receptors to identify food, mates, predators and provide bothidentify food, mates, predators and provide both sensual pleasure (the odour of flowers andsensual pleasure (the odour of flowers and perfume) as well as warning of danger (spoiledperfume) as well as warning of danger (spoiled food, chemical dangers).food, chemical dangers).
  • 3. A Wide Variety of Organic Compounds areA Wide Variety of Organic Compounds are Detected by OlfactionDetected by Olfaction Human beings can detect and distinguish thousand of different compounds by smell, often with considerable sensitivity and specificity. Most odourants are relatively small organic compounds with sufficient volatility and they can be carried as vapours into the nose. Figure 1 : Structure of different organic molecule
  • 4. The shape of the molecule rather than itsThe shape of the molecule rather than its other physical properties is crucialother physical properties is crucial Figure2 : Structure of different organic molecule
  • 5. General Physiology of OlfactionGeneral Physiology of Olfaction  The olfactory region consist of ciliaThe olfactory region consist of cilia projecting down, out of the olfactoryprojecting down, out of the olfactory epithelium into a mucous layer.epithelium into a mucous layer.  The mucous layer is produced byThe mucous layer is produced by Bowman’s gland, which resides inBowman’s gland, which resides in the olfactory epithelium.the olfactory epithelium.  Odorants are volatile chemicalOdorants are volatile chemical compounds, carried out by inhaledcompounds, carried out by inhaled air to the Regio olfactoria (Olfactoryair to the Regio olfactoria (Olfactory epithelium) located in the roof ofepithelium) located in the roof of the two nasal cavities of the nose.the two nasal cavities of the nose.  In the olfactory epithelium, olfactoryIn the olfactory epithelium, olfactory receptor neurons are present. Eachreceptor neurons are present. Each olfactory receptor neurons have 8-olfactory receptor neurons have 8- 20 whip like ciliary projection.20 whip like ciliary projection. Figure 3: The Main Nasal Epithelium
  • 6.  The olfactory receptor neurons extend through the epithelium to contact odorants inThe olfactory receptor neurons extend through the epithelium to contact odorants in the atmosphere, on the opposite side within the epithelium, the neuronal cells formthe atmosphere, on the opposite side within the epithelium, the neuronal cells form axons that are bundled in groups of 10-100 to penetrate the ethmoidal cribriformaxons that are bundled in groups of 10-100 to penetrate the ethmoidal cribriform plate of bone, reaching the olfactory bulb of the brain where they converge toplate of bone, reaching the olfactory bulb of the brain where they converge to terminate with post-synaptic cells to form synaptic structures called glomeruli. Theterminate with post-synaptic cells to form synaptic structures called glomeruli. The glomeruli are connected in groups that converge into mitral cells.glomeruli are connected in groups that converge into mitral cells.  Physiologically, this convergence increases the sensitivity of the olfactory signalPhysiologically, this convergence increases the sensitivity of the olfactory signal sent to the brain. From the mitral cells the message is sent directly to the highersent to the brain. From the mitral cells the message is sent directly to the higher levels of the central nervous system in the corticomedial amygdala portion of thelevels of the central nervous system in the corticomedial amygdala portion of the brain (via the olfactory nerve tract) where the signaling process is decoded andbrain (via the olfactory nerve tract) where the signaling process is decoded and olfactory interpretation and response occurs.olfactory interpretation and response occurs. Figure4 : Cells and connection of olfactory epithelium and olfactory bulb
  • 7. The Trigeminal Sense in theThe Trigeminal Sense in the Olfactory EpitheliumOlfactory Epithelium It must also be recognized that the olfactory epithelium contains another sensory system in the form of "Trigeminal Nerve" receptors, present in mouth, eyes and nasal cavity. A number of trigeminal chemical stimulants produce effects described as hot, cold, tingling or irritating. For examples --- ChemicalsChemicals leavo menthol or (-) menthol cold (at moderateleavo menthol or (-) menthol cold (at moderate concentration)concentration) hot (at high concentration)hot (at high concentration) allyl isothiocyanate --- mustard, mustard oilallyl isothiocyanate --- mustard, mustard oil capciacin --- hot Chile powder, mace spraycapciacin --- hot Chile powder, mace spray diallyl sulfide --- oniondiallyl sulfide --- onion
  • 8. The Odorant BindingThe Odorant Binding ProteinsProteins In 1979, Steven Price & coworkers and later Fesenko. et. al. found a number ofIn 1979, Steven Price & coworkers and later Fesenko. et. al. found a number of “Odorant Binding Protein” (OBP) for odorant chemicals such as ---“Odorant Binding Protein” (OBP) for odorant chemicals such as --- 5-a-ANDROST-16-EN-3-ONE Figure 5 : Different odourant binding protein
  • 9. Function Of OBPFunction Of OBP  They bind lipophilically to odorants inThey bind lipophilically to odorants in the aqueous / lipid mucousthe aqueous / lipid mucous increasing the concentration andincreasing the concentration and facilitate in transport.facilitate in transport.  They bind to ligand and receptors &They bind to ligand and receptors & assist in transport.assist in transport.  They act as a kind of filter to preventThey act as a kind of filter to prevent excessive amounts (over stimulation)excessive amounts (over stimulation) from reaching the receptors.from reaching the receptors.  The role of OBPs become clear inThe role of OBPs become clear in 2000 with characterization of human2000 with characterization of human lipocalins involvement in odorantslipocalins involvement in odorants bindings.bindings. Figure 6: Partial structure ofFigure 6: Partial structure of Human OPB IIaHuman OPB IIa modeled against 1EW3A (CRYSTALmodeled against 1EW3A (CRYSTAL STRUCTURESTRUCTURE OF THE MAJOR HORSE ALLERGENOF THE MAJOR HORSE ALLERGEN EQU C 1)EQU C 1)
  • 10. Odorant or olfactory receptor (OR)Odorant or olfactory receptor (OR)  In 1991, Linda Buck andIn 1991, Linda Buck and Richard Axel discoveredRichard Axel discovered both the family ofboth the family of transmembrane proteins,transmembrane proteins, called odorant receptors.called odorant receptors. The proteins contained the 7The proteins contained the 7 helical transmembranehelical transmembrane structure and have sequencestructure and have sequence similarity to other memberssimilarity to other members of the G-protein family.of the G-protein family.  Recently (2000), DoronRecently (2000), Doron Lancet & co-workers at theLancet & co-workers at the Weizmann Institute ofWeizmann Institute of Science Crown HumanScience Crown Human Genome Center haveGenome Center have constructed a database ofconstructed a database of human olfactory receptorhuman olfactory receptor genes present in differentgenes present in different chromosomes.chromosomes. Figure 7 : 7-transmembrane olfactory receptor
  • 11. Figure 8 : Human olfactory receptor genes by chromosome location
  • 12. Molecular events in OlfactionMolecular events in Olfaction  The olfactory stimulus arrives at the sensory cells by diffusion through air.  The odorant molecule binds directly to an olfactory receptors or to a specific binding protein that carries the odorant to a receptor.  Interaction between odorant and the receptor triggers a change in receptor conformation that result in the replacement of bound GDP by GTP on G- protein (Golf).  The activated Golf then activates adenyl cyclase of the ciliary membrane, which synthesize cAMP from ATP, raising local [cAMP].  The cAMP gated Na+ and Ca++ channels of the ciliary membrane open and the influx of Na+ and Ca++ produce a small depolarization called receptor potential.  if a sufficient number of odorant molecules encounter receptors, the receptor potential is strong enough to cause the neuron to fire an action potential. This relayed to brain in several stages and registers as a specific smell. These events occur within 100-200 ms.
  • 13. Figure 9 : Molecular events of Olfaction
  • 14. Other second messengers inOther second messengers in olfactionolfaction  Inositol triphosphate (IPInositol triphosphate (IP33 )actively participate in)actively participate in olfactory transduction with in certain mammals.olfactory transduction with in certain mammals.  Recent evidence is that the cAMP is mediated byRecent evidence is that the cAMP is mediated by another cyclic nucleotide cGMP.another cyclic nucleotide cGMP.  NO modulate cGMP concentration in mitral cells.NO modulate cGMP concentration in mitral cells.  Similarly carbon monoxide (CO) serves as aSimilarly carbon monoxide (CO) serves as a gaseous neuronal messenger linked to cGMPgaseous neuronal messenger linked to cGMP production.production.
  • 15. ConclusionConclusion So from this discussion we can say that olfaction is very important forSo from this discussion we can say that olfaction is very important for us and also for other animals.us and also for other animals. Dog’s sense of smell is 1000 times more than humans. People useDog’s sense of smell is 1000 times more than humans. People use dog’s keen sense of smell in many ways---dog’s keen sense of smell in many ways--- i.i. Govt. agencies use specially trained dogs in search and rescueGovt. agencies use specially trained dogs in search and rescue missiomissio ii.ii. Detection of narcotics.Detection of narcotics. iii.iii. Detection of forensic cadaver material.Detection of forensic cadaver material. Due to lack of smell the following disorders may be seen---Due to lack of smell the following disorders may be seen--- Anosmia : lack of ability to smellAnosmia : lack of ability to smell Hyposmia- decreased ability to smellHyposmia- decreased ability to smell Phantosmia- [“hallucinated smell”] often unpleasant in naturePhantosmia- [“hallucinated smell”] often unpleasant in nature Dysosmia- things smell differently than they should.Dysosmia- things smell differently than they should. Hyperosmia- an abnormally acute sense of smellHyperosmia- an abnormally acute sense of smell Some times olfaction serve as marker for Perkinson’s diseases. SomeSome times olfaction serve as marker for Perkinson’s diseases. Some illness can be diagnosed by their associated smell( e.g. acetone andillness can be diagnosed by their associated smell( e.g. acetone and diabetes). So smell therapy and clinical use of odour is an area fordiabetes). So smell therapy and clinical use of odour is an area for future.future.
  • 16. AcknowledgementAcknowledgement  Thanks to Dr. Prof John Kerry, University of London for giving me constant encouragements and suggestions whenever it is necessary.  Other Professors and Scholars of my department, to whom I am indebted for various courtesies.  The liberal assistance of the non – teaching staffs and technical assistance of our Technical Assistant of our Department is also acknowledged.  I am thankful to my entire colleagues for encouragement and appreciations and their co – operations.  Lastly, but not the least, I would like to express my gratitude to my parents and my sister for their constant encouragements and blessings on me.