INTRODUCTION:Olfactory receptors are presents in every vertebrate which areinvolved in the process of olfaction. It is a crucial process which helps inthe eating. Detecting prey or any danger, recreation, detections and overalllife style of living of an individual.
The major component of olfactoryreceptors is olfactory neurons which are explained in followings. Olfactoryreceptors genes are much higher in dogsand rodents as compared to other vertebrates.Olfactory neurons:The numbers of olfactory neurons in humans being are about tenmillion.
In vertebrates the olfactory neurons are located in the epithelium ofthe olfactory receptors in the nasal cavity. The cell builds of the ORNs aredispersed amongst all three of the stratified deposits of the olfactoryepithelium.Structure:Miniature hair-like cilia project from the olfactory receptor cell’sdendrite which ends into the mucus casing the exterior of the olfactoryepithelium. A very special protein of G type covered the cilia of the olfactoryneurons. Each olfactory receptor cell states only one type of olfactoryreceptor (OR), but many separate olfactory receptor cells express ORs whichbind the same set of odors.
The axons of olfactory receptor cells which expressthe same OR converge to form glomeruli in the olfactory bulb.Function:ORs, which are positioned on the membranes of the cilia, have beencategorized as a complex type of ligand-gated metabotropic channels.Approximately 1000 different kind of genes code for olfactory receptor whichmake them larger gene family. The odor of an odorant first dissolves in themucus lining of the olfactory epithelium and then binds to an OR. The affinityof olfactory receptor is vast and it can bind variety of different kind of odormolecules.it is the main cause of the alterations in activation patternsresulting in unique odorant profiles. The activated OR as a result activatesthe intracellular G-protein, GOLF (GNAL), adenylate cyclase and production ofcyclic AMP (cAMP) opens ion channels in the cell membrane, resulting in aninflux of sodium and calcium ions into the cell, and an efflux of chlorideions.
Neuron becomes depolarize as a result of influx of positive ions andefflux of negative ions, causing an action potential.Desensitization of olfactory neuron:Negative feedback response of olfactory neurons is very fast ondepolarization. At the time of neuron depolarizing, the CNG ion channel is openpermitting sodium and calcium to flash into the cell. The calcium influxactivates a flow of actions within the cell.
Calcium first binds to calmodulinto form CaM. Cam will stop the sodium and calcium influx when cam binds to theCNG channel and close it. CaMKII, which will phosphorylate ACIII and decreasecAMP production, is activated upon the presence of cam. CaMKII will alsoactivate phosphodiesterase, which will then hydrolyze cAMP. The overall resultof this negative feedback is that it stops the neuron from further activationwhen a new molecule of new odor came into the systemNumber of distinguishable odors:According to the scientific research humans can detect about more thanone trillion vast types of odors.
There are disputes on these findings asscientists believe that there are flaws in understanding the olfaction process.Moreover more research is needed to know the exact number of the odors whichhumans can detect. Olfactory Cilia and Disease:Now Days it is assessed that 3–6 million people suffer from overall orclinicalAnosmia in the United States alone. It can also be a miscalculate ofthe factual number of circumstances, as people are shy and mostly not reportedthe lost or transformed sense of smell to their medical doctor. A defect inolfactory functions can decrease the quality of life and most probably makespeople mood swings. Although the foremost causes of smell disorders in patientsarise following head trauma, upper respiratory tract infections, and chronicrhino sinusitis, olfactory dysfunction owing to genetic mutations orneurodegenerative disorders affecting cilia are becoming gradually morerecognized and better studied.Head trauma:The trauma of head of all ages is the major cause of the loss of thesense of smell in patients.Presently, the largest prevalence of head trauma occurs during a caraccident52%), with nearly 25% of these cases have malfunctioned olfactoryfunctions.
The rigorousness ofthe olfactory loss is directly connected with theseverity of the head trauma and period of any posttraumatic amnesia.The three main causes for the loss of the functions are explained mostprobably because of :(1) Skull or facial fractures causing the interruption of the Sinonasal tract;(2) Cutting or tearing of the olfactory nerve bundles(3) Hemorrhage of the brain region which includes the surrounding ofolfactory bulb or within the bulb. Chronic rhinosinusitus:The inflammation of the nasal cavity or mucosa is called as chronicsinusitis which occurs for at least 12 weeks and is linked with both allergicand nonallergic rhinitis. The nasal polyps can also be a cause. Representativesymptoms of chronic rhino sinusitiscompriseof nasal obstruction and mucosaldischarge which cause defects in olfactory functions. Theseanosmia’s affectnearly 10 million people world- wide and account for approximately 25% of allsmell loss cases.
Chronic rhinosinusitus can be occurring due to:(1) Injury of the olfactory mucosa(2) Inflammation and loss of the OSNs in the epithelium of olfactory.Mechanism:Olfactory receptors show affinity for a range ofodor molecules and different olfactory receptors may bind to a single odorantmolecule that depends on physio-chemical properties of molecules like theirmolecular volumes. Oncethe odor receptor has bound to odorant, structural changesoccur in receptor molecule and it binds and activates the olfactory-type Gprotein on the inside of the olfactory receptor neuron. The G protein (GolforGs) activates the lyase-adenylate cyclase which turnsATP to cyclicAMP (cAMP). The cAMP opens cyclic nucleotide gated ion channels that allow thecalcium and sodium ions to enter into the cell, depolarizing the olfactoryreceptor neuron and initiating an action potential that carries information tobrain.Primary sequences of varieties of olfactory receptorsare known from the genomes of various organisms.These are seven helixtransmembrane proteins.
The exact structures of these proteins are stillunknown. Their sequences exhibit typical class A GPCR motifs that are usefulfor building their structures with molecular modeling.In an advanced explanation, it has been explainedthat olfactory receptors could really sense various vibrational energy-levelsof a molecule rather than structural motifs by quantum coherence mechanisms.
Inevidence of this explanation it has shown that flies can differentiate betweentwo different odor molecules that only vary in hydrogen isotope. Besidedifferentiating between deuterated and non deuterated forms of an odorantmolecule they can also generalise the properties of deuteratedness.It is claimed that human olfactory receptors candifferentiate between deuterated and nondeuterated isotopomers ofcyclopentadecanone bysensing vibrational energy level.
On the other hand thisclaim was challenged by another report that human muskrecognizing receptor(OR5AN1) thatstrongly responds to cyclopentadecanone and muscone fails todifferentiate isotopomers of these compounds in vitro. It was then concludedthat the proposed vibration theory does not apply to the human musk receptorOR5AN1and other olfactory receptorsThis later study was also then criticizedthat it used cells in a dish rather examining within organisms i.e. applied invitro method of examination.Evolution:The olfactory receptors in vertebrates have shownto evolve by genomic mutation events such as gene duplication and geneconversion. Evidence in favor of gene duplication is provided by the fact thatmany olfactory receptor genes belong to the same phylogenetic origin that arelocated in the same gene cluster.Primates have a relatively small number offunctional OR genes as compared to other mammals. The recent hypothesis assumedthat functional OR genes can be correlated to the olfactory ability of a givenorganism.
In this sense decrease in the number of functional OR genes can causea reduction in the sense of smell.Species with higher pseudogene fraction wouldalso have a decreased olfactory ability. This assumption was flawed as dogsthat are reputed to have good sense of smell do not have the largest number offunctional OR genes. In addition pseudogenes may be functional. 67% of human ORpseudogenes are expressed in the main olfactory epithelium where they haveregulatory roles in gene expression.Applications:· Olfactoryreceptor neurons have enormous applications in environmental aspects and in infood quality checking.· Smells are sensed by olfactory sensory neurons in the olfactory epithelium invertebrates.
The olfactory epithelium iscomposed of six different types of cells differing in morphology and inbiochemical properties.· On the other hand in insectssmells are sensed by olfactory sensory neurons in the chemosensory sensilla that are present in insectantenna, palps and tarsa and on other body parts of insects. Odorants enter intothe cuticle pores of chemosensory sensilla and get attached with insect odorantbinding proteins (OBPs) before activating the sensory neurons that areresponsible for detecting sense of smell.· Olfactory receptors are able to detect air-borneodour molecules that enter the nasal cavity and bind to olfactory receptors.The activation of olfactory receptors results in olfactory receptor neuronssending an impulse to the brain’s olfactory system.· Olfactory receptors are key components in signaltransduction. The sequence and structural analysis of olfactory receptorsprovides deep insights to understand their function. In this work, we havesystematically analyzed the relationship between various physical, chemical,energetic and conformational properties of amino acid residues, and the changeof half maximal effective concentration (EC50) due to amino acid substitutions.
We observed that the odorant molecule (lignad) as well as amino acid propertiesare important for EC50. The inclusion of neighboring residues information ofthe mutants enhanced the correlation. Further, amino acid properties have beencombined systematically and we obtained a correlation of 0.90-0.98 withfunctional data for different (goldfish, mouse and human) olfactory receptors.Disorders:The following are disorders of olfaction or olfactory receptors:ü Anosmia “inability to smell” o Anosmia may be temporary, but some forms suchas from an accident, can be permanent.
o Anosmia is due to a number of factors,including an inflammation of the nasal mucosa, blockage of nasal passages or adestruction of one temporal lobe. ü Dyosmia “things smell different frommemory or expectation”o Dyosmia is a disorder described as anyqualitative alteration or distortion of the perception of smell.o The cause of dysosmia has not been determined but there havebeen clinical associations with the neurological disorder:§ Upper respiratory tract infection (URTIs)§ Nasal and paranasal sinus disease§ Toxic chemical exposure§ Neurological abnormalities§ Head trauma§ Nasal surgery Tumors on the frontal lobe or olfactory bulb§ Epilepsy ü Hyposmia “decreased ability to smell”o A related condition is anosmia, in which no odors can bedetected.o Some of the causes of olfaction problems are allergies, nasal polyps, viral infections and head trauma. It is estimated that up to 4million people in the UnitedStates have hyposmia or the related anosmia.
o Hyposmia might be a very early sign of Parkinson’s disease. Hyposmia is also an early and almost universal findingin Alzheimer’s disease and dementiawith Lewy bodies. Lifelong hyposmia could be causedby Kallmann syndrome.ü Parosmia ” things smell worse than theyshould” o One method used toestablish parosmia is the University of Pennsylvania SmellIdentification Test, or UPSIT. “Sniffin’Sticks” are another method that can be used to properly diagnose parosmia.These different techniques can also help deduce whether a specific case ofparosmia can be attributed to just one stimulating odor or if there is a groupof stimulating odors that will generate the displaced smell.o Fortunately forpatients afflicted with parosmia, symptoms usually decrease with time. ü Phantosmia”hallucinated smell” often unpleasant in nature.
o It can occur inone nostril or both.o Olfactoryhallucinations can be caused by common medical conditions such as nasalinfections, nasal polyps, or dental problems.o It can result fromneurological conditions such as migraines, head injuries, strokes, Parkinson’s disease, seizures, or brain tumors.
o It can also be asymptom of certain mental disorders such as depression, bipolar disorder,intoxication or withdrawal fromdrugs and alcohol, or psychotic disorders. Environmentalexposures are sometimes the cause as well, such as smoking, exposure to certaintypes of chemicals (e.g., insecticides or solvents), or radiation treatment for head or neck cancer.
Conclusion:Olfactory receptors belong to the super family of G-protein-coupledreceptors (GPCRs), which are characterized by seven transmembrane helicalregions. Olfactory receptors are responsible for checking sense of smell.Different disorders are also associated with olfactory receptor neurons. Genemutations and gene duplications are involved in evolution of olfactoryreceptors.