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Seminars in Cell & Developmental Biology

Takumi Misaka∗

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan





                  Sweetness, the most popular of the basic tastes, is representatively derived from carbohydrates, a source of energy commonly found in our daily foods, and the sweet sensation also acts as a nutritionally important signal. However, excessive intake of carbohydrates may cause lifestyle-related diseases. The most known of which is diabetes.

                  These current nutritional crises have led to the development of low-calorie sugar substitutes. Various artificial sweeteners have been developed to date and are widely used in food industrial products, such as soft drinks and confectioneries. Typical examples of sweet substances include saccharides, such as sugar; amino acids, such as glycine and d-tryptophan; and artificial sweeteners, such as aspartame and saccharin.

                  Most proteins, which are macromolecules, tend to be flat in taste, but some proteins, such as monellin and thaumatin, are known to be intensely sweet. These sweet-tasting proteins may be used as low-calorie sweeteners because they are perceived by humans as intensely sweet, but have almost no calories.


1 - Mechanism of action of MCL on the human sweet taste receptor

                  A. Activation of sweet taste receptors by pH reduction

Based on the phenomenon that a sweet sensation is evoked every time an acidic solution is consumed after MCL has been taken into the mouth. MCL is bound to the membrane of taste cells near the sweet receptor site. The receptor membrane undergoes a structural change in the presence of protons (H+), causing the sugar part of the MCL molecule to bind to the sweet receptor site in the membrane, thereby evoking a strong sensation of sweetness. In other words, the basis of the sweetness-inducing behaviour under acidic conditions are the pH-dependent conformational changes of the receptor membrane that detect the sweet sensation.


Interestingly, the acid-induced sweetness of MCL was diminished in the presence of a sweet taste inhibitor, lactisole. Lactisole is known to specifically inhibit the human sweet taste receptor.

                   B. Effects of MCL on the human sweet taste receptor

As described above, an evaluation system using cultured cells functionally expressing the human sweet taste receptor uncovered the taste-modifying mechanism of MCL, i.e., the modification from sour to sweet taste. The results basically supported the sweetness-inducing mechanism of MCL suggested by the MCL activation model proposed over forty years ago which reaffirms the insights of our visionary predecessors.


2 - Conclusion

                  As described above, the development of an assay system using cells expressing the human sweet taste receptor permitted us to uncover a more complete picture of the unusual properties of MCL, i.e., modifying taste perception from sour to sweet.

                  The sensation of sweetness evoked by MCL is refined and very pleasant. In addition, the development of a safe, novel calorie-free substance that tastes sweet would be ideal for those who suffer from lifestyle-related diseases. Thus,taste-modifying proteins have also been attracting attention in the food industry. The successful production of active MCL using Aspergillus oryzae, lettuce, or tomatoes as a host has recently been reported. Therefore, MCL may have promise in the near future as a new low-calorie sweetener or to modify the taste of sour fruits.


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