By David N. Leff

Your tongue can tell apart the five flavors ¿ bitter, sweet, sour, salty and umami ¿ that tickle your sense of taste.

Umami?

That little-known fifth factor of gustation, explained neurobiologist Robert Margolskee at Mt. Sinai School of Medicine in New York, ¿is a Japanese word used to describe the unique taste of glutamate and other amino acids. Umami¿s own special taste sensation lies somewhere between sweet, salty and indescribable. It¿s likely to be savored,¿ he added, ¿in chicken soup, crab meat, sea urchin roe and a number of other protein-rich seafoods.

¿Monosodium glutamate ¿ MSG ¿ is a umami stimulant,¿ Margolskee pointed out, ¿and is added to many cuisines to enhance their flavor. And it¿s not clear whether MSG and other umami stimuli act to enhance sweet, salty and other tastants, or whether they have their own matchless taste ¿ or a combination of the two.¿

Taste perception varies among individuals. Bitter, sour and salty are readily recognized, as are sweet and umami. Receptor proteins ¿ taste receptors ¿ on neuronal-like epithelial cells in the tongue¿s taste buds distinguish among them. Over the past few years, receptors and signaling proteins responsible for bitterness have been identified, but until now, identity of the sweetness receptor has been a black box. Now its lid has been lifted a bit.

Margolskee is senior author of a paper in the May 2001 issue of Nature Genetics, which reports: ¿Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac.¿

By editorial coincidence, a similar article appears in the May 2001 issue of Nature Neuroscience. Its title: ¿A candidate taste receptor gene near a sweet taste locus.¿ That article¿s senior author is neurobiologist Linda Buck at Harvard Medical School in Boston.

¿Our two papers,¿ Margolskee observed, ¿are largely complementary. The important conclusions are gratifyingly in common ¿ identification of the same receptor in mice and humans.

¿The key finding of our Nature Genetics paper,¿ he told BioWorld Today, ¿is that this sweet tooth receptor corresponds to a gene or a locus previously known in mice as Sac ¿ for saccharine responsiveness. This Sac locus regulates taster¿ vs. non-taster¿ mouse strains ingesting saccharine-sweetened or sugar-sweetened solutions.

¿We found that this receptor occurs in mice,¿ Margolskee continued, ¿that there are different forms of the receptor in sweet-preferring animals vs. sweet-indifferent ones. This has given rise to it as the sweet-tooth gene. In the specific sequence of the receptor there are two amino acids that we predict differentiate the taster from the non-taster form, with specific mutations that would alter function in a taster vs. a non-taster mouse.¿

Making Mice Reveal Their Sugary Little Secret

Getting the mice to confide their gustatory predilections, Margolskee recounted, ¿could be done very easily in a simple behavioral assay. We looked at eight different inbred strains of mice, which fell into four taster and four non-taster cohorts. They were inbred animals selected for other traits. It just turned out we could categorize them as sweet-preferring and sweet-non-preferring.¿

To acquire this privileged information, the co-authors put a mouse in a cage with a bottle of water and a bottle of sugar-sweetened solution, then measured how much of each liquid it drank. That afforded a measure of its sweet preference. By thus interrogating 10 tasters and 10 non-tasters, they obtained a dose-response curve that showed an order-of-magnitude difference in sensitivity between the two preference groups. ¿It took about 10 times more sugar or saccharine to elicit a preference response in the non-taster mice,¿ Margolskee recalled.

¿In another experiment,¿ he went on, ¿we recorded from the taste nerves of their tongues, as stimulated by sweetened solutions, and noted that there was a more robust response in the taster mice than in their non-taster matched controls. This led us to infer that there was less receptor signal in the sweetness-indifferent animals, perhaps because the receptor protein itself was less functional.

¿This receptor also exists in humans,¿ Margolskee pointed out, ¿so presumably people with a sweet tooth vs. people without one have differences in this particular gene ¿ something we¿re following up on.

¿These impending studies,¿ he observed, ¿are a potential collaboration with investigators at Monell Chemical Senses Center, a research institution in Philadelphia devoted to studying the chemical basis of taste and smell. They have already started such a survey, recruiting human subjects with differing responsiveness to sweet solutions.¿

Converting Non-Tasters And Vice Versa

¿We think it very likely,¿ Margolskee suggested, ¿that this receptor we¿ve identified is a sweet-taster receptor. It probably binds sugars, artificial sweeteners and amino acids that may taste sweet. This must be proven by biochemical experiments, but it¿s a reasonable expectation based on the data we have.¿

He foresees that data pointing ¿ distantly ¿ ¿to three or four practical outcomes.¿

For example, ¿someone who is indifferent to sweeteners, and would like to have more sweetness in their life, can have their receptor activity stimulated.¿

¿Another case,¿ he cited, ¿which happens fairly frequently, is in the elderly population, which with time experiences a decrease in taste and olfactory acuity. So savoring foods has diminished for many elderly individuals. Their food intake goes down, and then their nutritional status is compromised.

¿Finally, and I think this is the most speculative,¿ Margolskee proposed, ¿there are people who have the taster form of this receptor, and this has contributed to their over-eating and over-preference for sweets, leading to obesity and related diseases, such as diabetes. There might be a way to turn down the activity of their receptor protein, and convert these individuals from tasters to non-tasters, in this way, perhaps, helping them control their diet and obesity.

Five years ago, Margolskee co-founded Linguagen Inc. in Paramus, N.J, a biotech company aimed at modifying flavors ¿ particularly blocking the bitter taste of oral pharmaceuticals.

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