Smell and Taste UPDATES

Animal Smelling —

Mammals rely heavily on olfaction to interact adequately with each other and with their environment. The mammalian olfactory system recognizes diverse chemical stimuli conveying information about such things as food quality, the genetic identity or sexual status of potential mates, and even stress. A paper by Riviere et al in Nature May 2009 ) describes the identification of a chemosensory neuron in the rodent nose that responds to stimuli associated with cell damage, disease and inflammation, These results should help us to understand how animals identify pathogens or assess the health status of potential partners.

Until recently it was believed that the olfactory system of most mammals was of 2 types: a main olfactory system that detects environmental odours, for instance those emitted by food or predators, and an accessory (vomeronasal) olfactory system that detects pheromones – intraspecies chemical signals that elicit a stereotyped behavioural or hormonal change. It is now clear that the sense of smell is much more complex. Indeed, the main and accessory olfactory systems each respond to both general odours and pheromones.

Each olfactory division contains several types of sensory cell identified by the receptors and other proteins they express, the connections they make in the olfactory part of the brain, and the chemical stimuli to which they respond. This diversity of sensory cells in the nose has given rise to the concept of olfactory subsystems, each dedicated to a particular chemosensory role.

In addition animals use olfaction to assess whether other organisms may be dangerous, or even to judge the health status of potential partners. Mice use olfactory cues to avoid potential mates that are infected with parasites’, whereas nematode wormsdevelop aversions to odours given off by harmful bacteria, thereby avoiding toxic food, However, although such olfactory-based aversion behaviours have been documented, no olfactory subsystem that is dedicated to the assessment of health status or disease has been identified in mammals.

They make use of seven transmembrane G-protein-coupled receptors to identify odorants and pheromones. These receptors are present on dendrites of olfactory sensory neurons found in the main olfactory or vomeronasal sensory epithelia, and are involved in the odorant, trace amineassociated receptor and vomeronasal type 1 receptor superfamilies. The newly described formyl peptide receptor-related genes and vomeronasal sensory neurons, are found in multiple mammalian species. They are similar to the four known olfactory receptor gene classes, these genes encode seven-transmembrane proteins, and are characterized by monogenic transcription and a punctate expression pattern in the sensory neuroepithelium.

Munger Noses within noses Nature vol 459, 521-2
Riviere et al 2009 Formyl peptide receptor – like proteins are a novel family of vomeronasal chemosensors Nature vol 459, 574-577

Bitter Taste —

The sense of taste provides animals with valuable information about the nature and quality of food. When animal experience a bitter taste this is a warning against the ingestion of toxic and noxious substances. The mechanism of this is through bitter taste receptors called T2Rs. The T2Rs are a family of approximately 30 different G-protein-coupled receptors (GPCRs) that are selectively expressed in the tongue and palate epithelium. Differences in T2Rs between species (human and mouse) can determine the selectivity of bitter taste responses. ( Mueller et al Nature 2005, 10th March vol 434 pp 225-9

Mice and humans have distinctive differences in their sensitivities to many bitter compounds

In mice (m)T2R5 is a high affinity receptor for cycloheximide (Cyx)

In humans (h)T2R16 is a receptor for (3-glucopyranosides (salicin and related compounds),

( h)T2R14 is a candidate receptor for picrotoxinin

(h)T2R44 and (h)T2R61/hT2R43 are receptors for denatonium, aristolochic acid and 6-nitrosaccharin

Several β-glucopyrano-sides evoke strong bitter taste in humans, yet mice are largely indifferent to these compounds

. Similarly, phenylthiocarbamide (PTQ, a well known bitter taste often used in human genetic studies, is ineffective in mice.

Mueller et al were able to confer human bitter taste responses on mice by introduction of human taste receptors.

.From Mueller et al Nature 2005, 10th March vol 434 pp 225-9

Earth Eaters —

Earth eating or geophagia has been practised for thousands of years. There are recordings of this practice from ancient Sumeria, Egypt and China.

Some nutritionists sympathise with the value of this supplement to the diet, usually a clay as there is a rich provision of silicon, aluminium and traces of iron, calcium and zinc. However the clay may bid trace elements and prevent their absorption, worsening a precarious nutritional status. Geophagia in communities with marginal nutrition geophagia may cause anaemia. Especially in women who can in some cultures be the last to eat at meals.

Other studies suggest that geophagia is desired by, and provides trace elements, to individuals deficient in a trace element.

It has also been suggested that clays act as a detoxicant, whatever that means.

Perhaps in some states e.g. pregnancy the earths just taste nice , filling and not harmful. Or causing sickness.

The studies on geophagia are very welcome. On the one hand there is ingrained folk tradition and ascribed virtues of say eating clay. The reasons for such a practice should be examined and tested scientifically. This is so necessary and welcome.

Such a course of action is in contrast to some vocal media pundits who make ill founded claims which are totally untested scientifically

Trevor Stokes Nature 2006, 444, 30th November 543-4

Experiencing Pleasantness —

It would appear that pleasure can be mapped.

According to Plassmann et al, “…a basic assumption in economics is that experienced pleasantness from consuming a good depends only on its intrinsic properties and on the state of the individual” .

By contrast, it is known by so-called marketers that experienced pleasantness can be influenced by “…changing properties of Commodities, such as prices, that are unrelated to their intrinsic qualities or to the consumer’s state.”

To further elucidate these discrepancies, Plassmann and colleagues proceeded to investigate the neural associations of experienced pleasantness, by assessing both the subjectively reported perceived pleasure and the modulated blood-oxygen-level-dependent signal in the medial orbitofrontal cortex of the brain, an area of the brain in which activity is associated with the perception of experienced pleasantness.

Subjects randomly tasted three different wines in a series of six tastings, during which the price of each wine was varied. Not only did the price of the wine influence the subjectively reported experienced pleasantness, but also the activity in several areas of the brain associated with behavioral ratings for taste, odors and music. There were no changes in activity in the areas associated with primary taste

These finding support the concept that experienced pleasantness is computed by the brain in a hierarchical manner that incorporates both actual sensory properties as well as expectations.

Stephen B Hanauer 2008 Experienced pleasantness. Nature Gastroenterology and hepatology vol 5,pp 119

Infant Tastes —

Taste is a major determinant of children’s food preferences, but much has yet to be known of its development with age. This includes the acceptance of tastes and their developmental changes over the first year, and to compare acceptance across tastes. It is important to know within-subject variability of acceptance across tastes.

In this very interesting study the acceptance of sweet, salty, bitter, sour and umami tastes was measured in three groups of forty-five 3-, 6- and 12-month-old infants looking at ingestion and liking scored by the experimenter.

For each taste, four bottles were used (water, tastant, tastant, water). Acceptance of each taste relative to water was defined using proportional variables based on ingestion or liking. Acceptance over the first year only evolved for sweet taste (marginal decrease) and salty taste (clear increase). At each age, sweet and salty tastes were the most preferred tastes. Reactions to umami were neutral. Sour and bitter tastes were the least accepted ones

During the first year, inter-individual variability increased for all tastes except salty taste.

Schwartz et al 2009 Developmental changes in the acceptance of the five basic tastes in the first year of life British J of Nutrition vol 102 pp 1375-1385

Infants: Taste: Preference: Reactivity

Insect Odour Reception —

The malaria mosquito, Anopheles gambiae, is involved in the deaths of about one million humans every year. The female mosquitoes feed on human blood and whilst sucking their victim’s blood the mosquitoes unwittingly transmit the malaria causing parasite that threatens half of the world’s population. The number of people world wide who get malaria each year is greater than the population of the United States’.

Human-derived odorants have a key role in the mosquito tracing their human food sources. Female mosquitoes find the odour of patients with malaria particularly attractive.

Some of the mosquito’s odorant receptors are tuned into human derived compounds eg indole, an important component of human sweat. The receptors respond to phenol, methylphenols and other aromatic compounds and 3–methylindole , an odorant that induces females of another mosquito species to lay eggs.

Leal WS , 2010, The treacherous scent of a human. Nature vol 464 2010

Carey et al 2010 Odorant reception in the malarial mosquito Anopheles gambiae , Nature vol 464 , 66-71

Lack of Sense of Smell —

If one had to chose a sensory faculty to loose, smell would rank above sight or hearing. Neverthe less it is an important loss. It is called anosmia and is said to affect 2 % of the population. Nevertheless few clinicians are interested in this problem. Such olfactory disorders may be secondary to nasal polyps. Damage to the nerves supplying the nose and viral infections are other causes.

Watts G 2007 Scent trials British Medical Journal 335, pp588-9

Smells And All That —

Smells are almost everywhere. They colour our lives and make for pleasure and repulsion and can influence our appetite and pleasure in eating.

The smell of a baby even its faeces and vomit have a soft smell which lacks offensiveness. The smell of a baby’s skin is so lovely.

As the child develops, smell depends on whether the child is male or female. Boys love nasty smells. Refuse to change socks, sometimes to wash only under duress and have a glory in farts and other malodorous smells. If a group of little boys are standing in a group chortling the odds are it is farts which is the subject under discussion. In general little girls at this stage are beginning to develop the civilising characteristics of the woman and already are attracted to pleasant smells whether this is in flowers, nature as a whole or artificial scents.

The growing male then adds in stale clothes, stale beer and wine and cigarettes to his malodour.

The halitosis appears and we have the odour picture. And a smelly dog.

In the kitchen we have the accumulation of the damp smells of old kitchens , overcooked cabbage, garlic , fish and other smells.

Old peoples bedrooms smell of old people.

In nutrition if one comes into a house that smells one is put off eating. Some cafes have a damp horrid heavy old fish smell.

Air fresheners smell just as horrid.

So the answer is anosmia or to open the windows when ever possible.

Taste and Heat —

Temperature has a strong influence on how we taste. The sweetness of diluted sugar solutions increases strongly with temperature. Merely cooling or heating the tongue is sufficient to cause sensations of taste in approximately 50% of subjects.

Several members of the TRP super family function as thermosensors and this has been studied by Talavera et al Nature 2007, vol 438, 1022- 1025 to attempt explain what is happening in the tongue. The TRP super family are Transient Receptor Potential channels .

TRPM5, is an intra-cellular calcium -activated, voltage-dependent channel of the TRP superfamily, and is highly expressed in taste buds of the tongue, where it has a key role in the perception of sweetness, umami and bitter tastes. Activation of TRPM5 occurs downstream of the activation of G-protein-coupled taste receptors and generates a depolarizing potential in the taste receptor cells:. Factors that influence TRPM5 activity are therefore expected to influence taste.

Talavera et al have shown that TRPM5 is a highly temperature-sensitive, heat-activated channel. Inward TRPM5 currents increase steeply at temperatures between 15 and 35 degrees centigrade

Increasing temperature between 13 and 35 degrees centigrade markedly enhances the gustatory nerve response to sweet compounds in mice. The strong temperature sensitivity of TRPM5 may underlie known effects of temperature on perceived taste in humans, including enhanced sweetness perception at high temperatures and ‘thermal taste’, the phenomenon whereby heating or cooling of the tongue evoke sensations of taste without any taste being involved.

Which is why a hot sweet cup of tea can taste so deliciously in certain circumstances. It’s the TRPM5 at work.

The Chemistry of Pungent Tastes —

Despite their highly dissimilar flavours, garlic, horseradish and cinnamon each can have a fiery taste. This pungency has been attributed to chemicals that activate a specific ion-channel protein, known as transient receptor potential ankyrin 1 (TRPA1). Activated TRPA1 facilitates the flow of ions into the endings of specialized neurons in the mouth and skin. This excites the neurons, resulting in local inflammation and a sensation of burning pain. The activation of many ion channels by chemicals involves a readily reversible binding of the stimulating molecules. New evidence shows that the spicy compounds found in the foods listed above activate TRPA1 in a different, and often more sustained, manner, by covalently attaching themselves to cysteine amino-acid residues on the channel protein. The TRPAl channel can be activated by an array of chemical and physical signals. There are a number of food constituents that act on TRPA1, as well as acrolein (an environmental irritant) and icilin (a substance that evokes a cooling sensation), each quite different structurally. TRPA1 can also be activated by several other cell-communication pathways, including G-protein-coupled signalling pathways and membrane depolarisation. All of this may be involved in cold-sensing and mechanosensation’.

The question is how can one channel be activated by so many and such varied stimuli? Macpherson and his colleagues in Nature 2007, vol 445, p 541 and discussed by Caterina Nature 2007 vol 445 p 491 note that many TRPAI stimuli are electrophiles capable of reacting with cysteine residues (albeit by different mechanisms). This property, rather than chemical geometry, night account for their shared activation of TPA1. They showed that the cysteine-reactive agonists must enter the cell before activating TRPAl. Covalent modification of these cysteines, individually or, together or in combination with others accounts for the activation of TRPAI by electrophiles. Only-one cysteine residue was identified as crucial, possibly reflecting subtle differences between species in overall TRPAI structure. Aside from the newly identified sites of electrophile action, the TRPAI N-terminal domain contains 18 ankyrin repeat motifs and an EF-hand domain. These two features have been proposed to contribute to the regulation of the channel by mechanical force and calcium ions, respectively. The duration of covalent TRPA1 activation differs between species. The lifetimes of covalent cysteine modifications can vary, depending on the modifying agent and on environmental factors such as pH or redox state and lead to differences in the duration, magnitude and qualitative features of TRPA1-mediated food pungency, inflammation and pain. Electrophilic agents can be damaging to DNA and proteins, one possible step towards cancer.

Many of the cysteine-reactive compounds that activate TRPA1 induce the expression of the enzymes that detoxify them protecting against such injury.


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