BIOCHEMISTRY OF OLFACTION

 Olfaction – the primal sense, forgotten sense, smaller role for humans
 Significance: alarm system (fire, smokers), flavor, communication (pheromones), social context (family,attractiveness)
 Mercaptan – smelly chemical + natural gas = smelly gas leak
 Pathway: Air passes olfactory epithelium with chemosensors  neurons in olfactory bulb  sensory cortex
 OSNs (olfactory sensory neurons) – specialized cells that detect gaseous molecules and produce an electrical signal
 Chemo-electrical signal transduction – turning chemical signal into electrical signal
 Transduction all located within sensory cilia of OSN

Odorants
 Volatile chemical compounds carried by inhaled air to olfactory epithelium
 Humans can smell 4K-10K odors
 Size of epithelium related to sense of smell = larger size means greater sense (humans 10 cm2 vs dogs 170 cm2)
 Molecular properties: water solubility, volatile, vaporizable, low polarity / non-ionic, lipophilicity, surface activity
 Each odorant activates a unique set of olfactory receptors; various receptors respond to discrete parts of an odor
structure; brain must determine the precise combination of activated receptors to distinguish a smell

Odorant Binding Proteins (OBP)

 Proteins in mucus layer that bind to odorants
 Proposed roles:
o Transporter – facilitates transfer of odorants across mucus layer to receptors
o Terminator – removes “used” odorants for degradation; Lipocalin – carrier proteins for hydrophobic molecules,
prevents receptor desensitization
o Protector – prevents over-stimulation of excessive odorants
 Human hOBP (IIa) – strongly expressed in nasal structures, salivary and lachrymal glands and lung, has an oral
sphere profile similar to lipocalins
 hOBP IIb – genital sphere

Olfactory Receptors
 humans 30 genes, some lost (converted to pseudogenes) during evolution
 one of the largest G-protein receptors, linked to cAMP and IP3
 part of 7TM receptor family (7 times passes membrane), odorant complemantarity determining regions in TM3, 4, 5
 odorant selectivity – has hundreds of different genes for odorant receptors, only one in each OSN

OBP and OR Interaction

 No odorant: OBP + OR with high affinity and relevance = Quiescent state
 Odorant-OBP + OR or OBP-OR complex  odorant released, activate OR or even displace OBP-OR complex
 High odorant concentration = OBP acts as scavenger, preventing binding site saturation and anti-desensitization

G-protein Activation
Odorant + OR activates G-protein Effect
ATP into cAMP  Ca influx = action potential  Ca opens Cl
AC G-olf
channels  electrical excitation
PLC Other G-protein production of IP3 + DAG  act on ion channels and ↑ Ca levels
Ca and GC activating protein Other G-protein produce cGMP  augments cAMP signal

 G-olf G-protein in receptor cells, similar to Gs, made up of α active portion, and β & γ regulatory subunits, α-GDP is
inactive, α-GTP is active
 α subunit has GTPase activity after activating AC = acts as regulatory mechanism
 Cl influx to generate potential is unusual, OSN actively accumulates Cl against electrochemical gradient

Adaptation
 Ca ions entering cyclic nucleotide-gated channels  Ca acts with calmodulin  ↓ cAMP sensitivity  requires
stronger odor stimulus to produce sufficient cAMP
 Acts via closing of Ca channels

Theories of Olfaction
Theory By Hypothesis
Molecular lock & key hypothesis of Moncrieff ability to bind depends on odorant shape and electrical charge
shape stereochemical theory of Amoore geometry of odorants = 7 primary odors
Davis and Taylor odorant molecules diffuses across membrane  ion pore
Diffusion pore
formation
Rosenberg carotenoids + odorants = semiconductor current  activate
neurons; Problems: receptors have no pigment and weakly
Piezo-effect odorous short chain alcohols gave greater increase in
semiconductor current than smellier long-chain alcohols.

Dyson receptors detect and respond to a vibration in the odorant,

Molecular
characteristic vibrations for discrimination; frequency is infrared
vibration
= different IR frequency means different smell
Turin OR + odorant = electron tunneling if vibrational mode of
Nose as a
odorants equals energy gap between filled and empty electron
spectroscope
levels; NADPH diaphorase action of receptor
 Electron tunneling – transfer of electrons down the backbone of CHON when:
o No odorant = unable to tunnel, oxidized disulfide bridge between OR and G-protein;
o Odorant present = electrons lose energy during tunneling by exciting its vibrational mode  disulfide bond
reduced  G-protein activation and cascade

Smells and molecules

 Structure-activity relationship approaches
o Using numbers – description of some aspect of an odor on a numerical scale
o Molecular features – osmophore – key odorant atoms or functional groups placed at certain distances = certain
binding according to molecular shape and composition
o Computer models – looking for patterns linking odors with features and properties

Smells and Steroisomerism

 Gemotric and optical isomerism = different fragrances
 Geometric isomers: Geraniol (waxy, sweet rose) and nerol – sweet rose with citrus
 Structural (positional isomer): Linalool – 2 optical isomers (L and R), R has bergamot and lavender
 Structural (functional isomer): Citronellal – aldehyde and 2 optical isomers, citrus, used in soap and insect repellants
 Optical Isomers: chiral, non-superimposable; D-carvone – caraway; L-isomer – spearmint

Disorders
Disorder Notes
temporary or permanent loss of smell, most common; due to head trauma, upper
respiratory infection or nasal/sinus disease; may be due to smoking, crooked nose /
Anosmia / Anosphrasia
septum, medication,s drugs, aging, lead poisoning, insecticides, radiation therapy,
idiopathic loss
Hyposmia / Partial
diminished sense of smell, after acute influenza
Anosmia
Dysosmia distorted sense of smell, smells non-existent unpleasant odors
Hyperosmia increased sensitivity to smell, neurotics or histrionics
Kallman’s syndrome genetic, anosmia + ↓ functional activity of gonads
inability to distinguish a particular odor due to fatigue or desensitization, test a max of 3
Odor fatigue
odors when testing fragrances

Other notes
 Astronauts = Capillary pressure = ↓ smell and taste
 Women can differentiate HLA alleles via smell; ↑ HLA = preference
 Amorphallus titanium – largest and smelliest (putrefying roadkill) flower, petals like rotting flesh, putrescin and
cadaverin
 GnRH develop in olfactory tract
 Vomeronasal Organ – bottom of nasal septum, active in animals, pheromone receptors, involuted in humans