(acetosuifam, sodium saccharin, rebaudioside and stevioside) tended to fall near one another with the amino acid d-tryptophan located a little farther away.
Physiology & Behavior, Vol. 23, pp. i-9. Pergamon Press and Brain Research Publ., 1979. Printed in the U.S,A.
Qualitative Differences Among Sweeteners S U S A N S. S C H I F F M A N , D E B R A A. R E I L L Y A N D T H O M A S B. C L A R K , III
Department of Psychiatry, Duke Medical Center, Durham NC 27710 Received 15 March 1979 SCHIFFMAN, S. S., D. REILLY AND T. CLARK. Qualitative differences among sweeteners. PHYSIOL. BEHAV. 23(1) 1-9, 1979.--Seventeen sweeteners varying widely in chemical structure were arranged in a three-dimensional space by two multidimensional scaling procedures, INDSCAL and ALSCAL. Fructose, glucose, sorbose, xylitol and xylose tended to fall near one another. Two sweeteners with a syrupy component, maltose and sorbitol, fell further away. Ca cyclamate and the dipeptide aspartame were the two artificial sweeteners which fell closest to and thus tasted most like the sugars. The proteins monellin and thaumatin, as well as the chalcone glycoside, neohesperidin dihydrochalcone, all have long aftertastes and thus tended to fall proximate to one another. Stimuli with the highest metallic and bitter ratings (acetosuifam, sodium saccharin, rebaudioside and stevioside) tended to fall near one another with the amino acid d-tryptophan located a little farther away. Adjective scales were related to the spatial arrangement. Wide variability in the patterns of intensity ratings over subjects suggests that the sweet taste may be mediated by several peripheral receptor mechanisms.
Sweeteners
Multidimensionalscaling procedures
AT THE present time, it is not possible to predict whether a molecule will impart a sweet taste by examining its chemical structure. Compounds which taste sweet vary widely in molecular structure: in addition, there may be different types of sweetness which vary in quality. A basic structural subunit, the AH-B system, has been proposed as a prerequisite for a compound to taste sweet, where A and B are electronegative atoms separated by 2.5 to 4.0 A, and H is a hydrogen atom which is part of a polarized system A-H [41,42]. According to this hypothesis, the "sweet molecule" interacts with a similar AH-B receptor system in the membrane, involving two simultaneous hydrogen bonds. Additional site(s) may also be necessary for a sweet taste. The D-isomer of an amino acid can have a sweet taste while the L-isomer does not, implying a stereoselective receptor or at least three bonding sites [43]. It has been observed that sweetness may depend on a hydrophobic bonding area [10] which has led to proposal of a third, so-called "dispersion" site to account for a potent sweet response [24]. The sensation of sweetness is quite complex and is frequently accompanied by other qualities as well [3,14]. Bitterness is often associated with simple sugars and glycosides which may be due to polar and lipophilic features as well as ring size and shape [4]. Sweet and bitter receptor sites could be proximate, accounting for molecules which taste both sweet and bitter [5]. Neurophysiological studies suggest that not all receptor sites which bind sweet-tasting molecules are identical [3]. Receptor sites for sweet-tasting compounds not only differ from cell to cell, but differ within a single cell as well. Two independent studies [2,28] have revealed that single neurons are not uniform in their responses to sugars; but, rather, the response characteristics vary from one cell to the next.
INDSCAL
ALSCAL
Spatialmolecular arrangement
Each of the above studies has introduced important factors for deepening our understanding of the relationship between sweetness and chemical structure. However, a strict understanding of the structure-activity relationships for the sweet taste which would allow us to design accurately new sweeteners has yet to be achieved. The search for new sweeteners has tended to begin with manipulation and modification of chemical structure, looking for a relationship to taste quality, i.e., sweetness. A reverse approach has recently been proposed [31, 32, 33, 36] which begins with making quantitative psychophysical measurements of the qualitative differences among tastes (or odors) in order to search for quantitative relationships to physicochemical parameters. This approach arranges chemical stimuli in spatial maps by a mathematical technique called "multidimensional scaling" (MDS) such that stimuli which are judged experimentally similar in taste (or smell) quality are arranged close to one another in the space. Stimuli judged phenomenologically dissimilar are located distant from one another. Utilizing this approach, it has been found [31, 32, 33, 36] that a series of physicochemical parameters (such as molecular weight, structure, functional group) can be weighted mathematically to provide more power for predicting sensory quality than a single factor alone. The purpose of this experiment is to delineate the psychophysical differences among sweeteners by utilizing MDS techniques. Multidimensional scaling techniques have previously been applied to psychophysical data in the chemical senses [31-40]. The spatial arrangement of sweeteners is examined with regard to individual differences among subjects, relation to adjective ratings, and relation to physicochemical parameters.
ZThispaper was supported in part by a grant to the senior author, NIA AG00443, and a grant to Dr. R. P. Erickson, NSF BNS75-22692. 2The authors would like to thank Dr. Michael Lindley and Dr. Guy Crosby for their reading of the manuscript.
Copyright © 1979 Brain Research Publications Inc.--0031-9384/79/070001-09502.00/0
2
S C H I F F M A N , REILLY AND C L A R K TABLE I SWEETNERS EMPLOYED INCLUDING CHEMICAL CLASSIFICATIONS,COMMERCIAL SOURCES, AND CONCENTRATIONS USED. CONCENTRATIONSOF SACCHARIDESAND POLYHYDRIC ALCOHOLS ARE GIVEN IN MOLARITY.CONCENTRATIONS OF THE REMAININGSTIMULI WHICH ARE GENERALLY CONSIDERED "ARTIFICIAL" SWEETENERS ARE GIVEN IN PERCENTAGES Classification
Source
Concentration Used
Oxathiazinone dioxide (methyl derivative); 3,4 dihydro-6-methyl-1,2,3 oxathiazin4-one-2,2-dioxide potassium salt Dipeptide: L-aspartyl-L-phenylalanine methyl ester Calcium cyclohexyl sulfamate Monosaccharide ketohexose Monosaccharide aldohexose Disaccharide Protein (MW 10,700)
Hoechst (German)
0.3YY(
Searle
0.25%
Monsanto Sigma Sigma Sigma Worthington and R.Cagan California Aromatics
0.6% 0.6M 1.1M 1.2M 0.025%
Compound Acetosulfam Aspartame Ca Cyclamate Fructose Glucose Maltose Monellin Neohesperidin dihydrochalcone Rebaudioside A Saccharin (sodium salt) Sorbose Sorbitol Stevioside Thaumatin d-Tryptophan Xylitol Xylose
Dihydrochalcone glycoside Diterpene glycoside o-sulfobenzimide: 1,2-benzothiazol-3(2H)-one- 1,1dioxide, Na + salt Monosaccharide ketohexose Polyhydric alcohol Diterpene glycoside Several distinct proteins (MW 18,000-21,000) D-Amino acid Polyhydric alcohol Monosaccharide aldopentose
METHOD Subjects
The subjects were 12 non-smoking undergraduate and graduate students at Duke University, aged 18--30, who were paid $2.50 per hour. Five of the students had previously been subjects in taste experiments. Stimuli
The 17 sweeteners used as stimuli were: acetosulfam (see Clauss et al. [9]), aspartame (see Mazur et al. [26]), calcium cyclamate, fructose, glucose, maltose, monellin (see Inglett [21], Morris and Cagan [29], Bohak and Li [6]), neohesperidin dihydrochalcone (see Horowitz and Gentili [17,18], DuBois et al. [121), sodium saccharin, rebaudioside A (see Khoda et al. [231, Kaneda et al. [22]), sorbitol, sorbose, stevioside (see Mosettig et al. [30]), thaumatin (see van der Wel [45], Hough and Edwardson [19]), d-tryptophan, xylitol, and xyiose. The compound classifications, commercial sources, and concentrations used are shown in Table 1. Some of the compounds were obtained from the sources listed by General Foods Corporation and provided for use in this study. The chemical structures are given in Fig. 1. Monellin, neohesperidin dihydrochalcone, stevioside, rebaudioside A, and thaumatin derive from natural sources. Monellin is a protein isolated from the fruit of the tropical plant Dioscoreophyllum cumminsii Diels (Serendipity Berry). Neohesperidin dihydrochalcone is prepared from
0.016%
Ajinomoto Logica International Corp.
0.07% 0.045%
Sigma Sigma Ajinomoto Tate and Lyle, Ltd. Sigma Sigma Sigma
1.2M 1.2M 0.09% 0.01% 0.3% 1.0M 1.3M
neohesperidin which is a flavanone found in Seville oranges, C. aurantium. Stevioside and rebaudioside A are isolated from the leaves of Stevia rebaudiana Bertoni, a wild herb found in Paraguay. Thaumatin is a protein derived from the fruit of the West African plant Thaumatococcus danielli Bentham. The stimuli were dissolved in deionized water. Natural sugars were prepared 36-48 hours prior to testing to allow mutarotational equilibrium to be established. The remaining stimuli were prepared just before use. Solutions were poured into plastic cups prior to testing and allowed to reach room temperature (72°F). Experimental Procedure
The experiment was divided into three parts: (1) intensity matching, (2)judgments of similarity, and (3)judgments on adjective scales. Intensity matching. In the first sessions, 10 ml of the stimuli at various dilutions were presented in 5 oz plastic cups. Subjects judged the overall intensity of each stimulus by marking an X along a 5-in. line as shown below: weak
strong
Intensity measures were taken as distances in 1/20 in. increments along the 5-in. line such that a rating at the " w e a k "
DIFFERENCES AMONG SWEETENERS
3 SORBITOL
MALTOSE
ACETOSULFAM
0=~/~
CHaOH CH2OH CH2OH CH2OH
3
CH2OH
CH2OH CH20~I
o
@ K
HO
(B"D- Maltose)
(ac-D-Maltose)
CH2~
H-¢'O MONELUN-PROTEIN
ASPARTAME o
SORBOSE
B-NEOHESPEREDINDIHYOROCHALCONE
•
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CH2-CH-NH-C-CH-NH 3
.o
/~-e
00CH 3
U
.o~-o o
OH
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__
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OH OH
cyclichemikeml
STEVIOSIOE
CH2OH
CALCIUMCYCLAMATE REBAUOIOSIOE CH2OH
FRUCTOSE
~,c., OH
yCH~OH
8-D'fructo'fu
..... '~
OH //' CH2OH
CH3
~-D-fructo-pyronose
HoI=O
OH
--OH --OH
THAUMATIN-PROTEIN CH3 -C,0
J
D-TRYPTOPHAN
HoI~O~C~IH2 OH OH
a "D" fructo" furanose
a -D-fructo-pyronose
GLUCOSE
O
CH2OH
O
o
e ONo 2
CH2
.N@
SACCHARIN(NoSALT) ~
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OH
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C,O
XYLITOL
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HoIOH OH
Cx'I OH
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CH2OH
¢ - D - ~ue~o~se
I~tdominont at c50 °
O%.H HO-
XYLOSE H,C,O
t °" OH OH
OHt
CH2OH
troce furonose ~ m $
~ OH OH
CH2OH FIG.
1. C h e m i c a l s t r u c t u r e s o f t h e s w e e t e n e r s
employed.
H O~ ~ O HO
4
S C H I F F M A N , R E I L L Y AND C L A R K
end of the line was transcribed as " 0 " and a rating at the " s t r o n g " end was transcribed as "100." The concentrations of stimuli which yielded ratings such that the geometric mean over subjects fell between 55 and 65 were considered to be approximately equal in intensity. It should be noted that the intensities were equated on overall impact and not on sweetness alone. Equating sweetness was found to be an impossible task for most subjects due to problems in separating " s w e e t n e s s " from other qualities of the stimuli as well as temporal patterns. It should also be noted that, although subjects gave idiosyncratic ratings (see Results and Discussion), the final concentrations employed were considered close enough in intensity by all subjects such that they reported that they were able to make similarity judgments based on qualitative differences among the stimuli. Judgments of similarity. The subjects, wearing nose plugs, were presented with pairs of stimuli by the experimenter. The subjects first tasted the solution in the cup on the left and then the solution in the cup on the right, rinsing well with deionized water in between cups. The subjects took all l0 ml of each stimulus in the cup into their mouths, swirling it as much as possible to allow it to come in contact with the entire oral cavity, including the back of the tongue. Stimuli were not swallowed, but rather they were ejected into a spittoon. After tasting the two stimuli of a pair, subjects made a rating of qualitative similarity along a 5 in. line: same
different
Ratings were transcribed from " 0 " to "100" in a manner analogous to those for intensity ratings. One hundred thirty-six judgments (C~r) were required to compare each stimulus with every other on the basis of qualitative similarity of taste. The time interval between presentation of two stimuli of each pair was approximately 30 seconds. The time interval between presentation of pairs was at least 5 minutes. Intervals of l0 or more minutes were required when monellin or thaumatin were used as stimuli. Twenty 1-hr sessions were needed to complete all the pairs. The order of presentation was counterbalanced so that each stimulus was presented first in a pair (i.e., it was the stimulus in the left cup) one half of the time. Judgments on adjective scales. After the subjects completed all the similarity judgments, they rated each of the sweeteners on a series of adjective scales previously used by Schiffman and colleagues [33, 34, 35, 36,371. The adjectives (such as " g o o d " - " b a d " ) defined the ends of a 5-in. line. Ratings were transcribed in a manner analogous to intensity and similarity judgments. Four additional adjectives not included in the above studies were employed as well: " s y r u p y , " "taste fades fast," "delayed sweetness," and "aftertaste." Subjects were also asked to make additional comments.
distances in the spatial map correspond to the rank order of the similarity judgments. Both procedures were employed to avoid making a priori assumptions about the level of measurement (ordinal, interval or ratio) appropriate to the similarity data. In addition to providing multidimensional maps of stimuli, ] N D S C A L and A L S C A L are individual differences models which provide weights for individual subjects on each of the dimensions of a multidimensional space common to all subjects. Solutions for individual subjects were also found using SSAI (see Guttman [15], Lingoes [25]). P R E F M A P (Carroll and Chang, see Carroll [8]) was used to relate adjective ratings to the multidimensional stimulus space. Phase 4 of P R E F M A P was used here to represent the mean adjective ratings over subjects as scale values along unit vectors in the multidimensional sweetener space. RESULTS
Similarity Space Derived by INDSCAL and ALSCAL Application of I N D S C A L and A L S C A L to the 12 similarity matrices for the 12 subjects yielded almost identical results, indicating that the solution was stable over various levels of assumed measurement type. The three-dimensional solution common for the 12 subjects is shown in Fig. 2. Cross-sections through the space are shown in Figs. 3a and 3b to aid in understanding the relationships among the stimuli in Fig. 2. A three-dimensional solution, which can be conceptualized geometrically, was considered best for representation of the sweeteners tested here because only one new relationship was revealed in solutions with higher dimensionality. Additional dimensions slightly separated xylose from the other monosaccharides (probably because of a slight sour component). It can be seen that fructose, xylose, sorbose, xylitol and glucose tend to group together in Fig. 2 (cf. upper left-hand quadrant in Fig. 3a). Aspartame, sorbitol and maltose are located nearby. Monellin, thaumatin and neohesperidin dehydrochalcone are separate from the "fructose a r e a " (cf. MALTOSE T d=-TRYPTOPHAN CoCYCLAMATE SORBtTOL STEVLOSIDE ACETDSULFAM
Na SACCHARIN
XYLiTOL
/
Analysis of Data The similarity data were analyzed by two multidimensional scaling procedures, I N D S C A L (Carroll and Chang [8]) and A L S C A L (Takane et al. [44]), which arrange stimuli in spatial maps such that sweeteners which were rated similar to one another are located proximate to one another in the map. I N D S C A L is a metric procedure which makes the assumption that the experimental similarity measures obey the restrictions of the interval or ratio level of measurement. A L S C A L has a nonmetric option which treats the experimental data at the ordinal level of measurement such that the
SO~61lOSE ASPARTAME
FIG. 2. Three-dimensional arrangement of sweeteners achieved by INDSCAL. Stimuli which were judged similar to one another experimentally are arranged close to one another in the space. Stimuli judged dissimilar are located distant from one another.
D I F F E R E N C E S AMONG S W E E T E N E R S
5
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orbitol
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FIG. 3. Cross-sections of the three-dimensional arrangement in Fig. 2: (a) Dimension I versus Dimension II (the floor of the model in Fig. 2): (b) Dimension I versus Dimension III. lower left quadrant of Fig. 3a). Acetosulfam, rebaudioside, stevioside and Na saccharin are located proximate to one another (cf. the lower right quadrant in Fig. 3a), with d-tryptophan located a little farther away (cf. Fig. 3b). Ca cyclamate is located intermediate between the sugars and acetosulfam, rebaudioside and Na saccbarin. Weight spaces which reflect individual subject differences are shown for the ] N D S C A L solution in Figs. 4a and 4b. The weight spaces are interpreted as follows. Individual subjects weight the dimensions of the space in idiosyncratic ways.
I
I -0 800
I
I - 0400
I
I
I 0 400
I
0
80/0
I
I 200
FIG. 4. Weight spaces derived by INDSCAL which indicate idiosyncratic stretching of the dimensions of the space in Fig. 2 by individual subjects. (See text for explanation.! (a) Dimension I versus 11: (b) Dimension I versus Dimension III. For example, subject 3 weighted dimension I, which is highly correlated with "sweet and bitter" adjective ratings, proportionately more than dimension 11 which is more highly correlated with "aftertaste." Thus, the appropriate multidimensional arrangement for subject 3 is similar to that in Fig. 2, but stretched out in an elliptical fashion along the first dimension. Subject 8 weighted dimension II relatively more than I so that the appropriate arrangement for this subject would be stretched in an elliptical fashion along dimension II. Individual solutions for each subject were found using SSAI [15,25]. The individual differences in relative arrangements of the points were found to be minor among subjects apart from idiosyncratic weighting or stretching of the axes.
Relation of the Adjective Ratings to the Similarity Space The adjective ratings as well as the comments were examined to explore their relationship to the spatial arrangement in Fig. 2. Most of the adjective scales employed were not found to be relevant (i.e., all sweeteners, were rated "not
6
SCH1FFMAN. RE1LLY AND CLARK SWEET
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FIG. 5. Histograms for 10 adjective scales which represent the range of ratings for the 12 subjects. For example, one subject's rating for acetosulfam on the "good-bad" scale was transcribed as a rating between 11 and 20: one subject's rating was transcribed between 21 and 30. The left side of the scale corresponds with the rating "good": the right side corresponds with the rating " b a d . "
DIFFERENCES AMONG SWEETENERS
7 WARMING
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,.,. Xylose
FIG. 5. continued. salty"). The remainder of the adjective ratings tended to be widely distributed over subjects across the scales. Histograms showing the variation of ratings on 10 adjective scales are shown in Fig. 5. Each circle corresponds to a rating by an individual subject in a given area along the scale. For example, in Fig. 5, one subject's rating for acetosulfam on the 5-in. "good-bad" scale was transcribed as a rating between 11-20: one subject's rating was transcribed from 21-30: two subjects' ratings were transcribed from 81-90, etc. The left side of the scale corresponds with a rating of "good": and the right side of the scale corresponds with a rating of "bad." The rank order ratings for stimuli on any given adjective scale showed that much wider individual variation was found when "language-based" adjective ratings were applied to the sweeteners than when "nonlanguage-based" similarity judgments were used. Although adjectives are not as stable a means of finding relationships among the sweeteners, they are helpful in understanding the reasons for the arrangement in Fig. 2 found using similarity judgments. The saccharides and polyhydric alcohols tended to fall close together and, in general, their tastes according to adjective ratings tended to develop fairly
fast with less aftertaste than the other stimuli. Sorbitol, fructose and glucose were, in general, considered good, natural, somewhat syrupy sweet tastes. Maltose was rated quite syrupy. Xylose and xylitol had slight unpleasant components (possibly sour for some subjects) which are difficult to characterize verbally. The tastes of thaumatin and neohesperidin dihydrochalcone developed slower than the other stimuli. The taste of monellin developed fast. The aftertaste of monellin lingered a long time, while the aftertaste for thaumatin and neohesperidin dihydrochalcone also lingered a long while for most subjects. One subject commented on a strong cooling effect of the aftertaste of neohesperidin dihydrochalcone. Many subjects found the aftertaste of neohesperidin dihydrochalcone and thaumatin to be unpleasant. Monellin had no unpleasant or bitter component. The highest bitter and metallic ratings were found for acetosulfam, Na saccharin, rebaudioside, stevioside and d-tryptophan. Ca cyclamate had a relatively good sweetness which was intermediate between Na saccharin and the saccharides in pleasantness. Aspartame also had a relatively good sweetness though several subjects detected a bitter component which developed with time.
8
S C H I F F M A N , R E I L L Y AND C L A R K
In order to further understand the psychological dimensions in the space in Fig. 2, P R E F M A P was applied to the geometric means of the adjective ratings in Fig. 5 to determine whether the adjectives could be projected into the similarity space. Direction cosines for the adjectives which yielded correlations above 0.80 between the geometric means for each stimulus on a given adjective scale with the projections of the stimuli on the directions through the space found by P R E F M A P for each adjective are given below:
good taste changes sweet
aftertaste
I
II
I11
- 0.639 0.424 -0.832
0.768 -0.898 0.409
0.051 -0.115 0.375
0.227
-0.933
0.281
Thus, it can be seen that the saccharides are seen as highest on " g o o d " and " s w e e t . " The thaumatin, neohesperidin dihydrochalcone, monellin group, in general, have the longest aftertastes. DISCUSSION
This study, using sweeteners which were adjusted in concentration such that mean intensity ratings were approximately equal, indicates that the saccharides tended to fall near one another. The polyhydric alcohols, xylitol and sorbitol, were separated somewhat from this group. Stimuli with long aftertastes (the proteins monellin and thaumatin, as well as neohesperidin dihydrochalcone) tended to fall proximate to each other. Stimuli with the highest metallic and bitter ratings (acetosulfam, Na saccharin, rebaudioside, and stevioside) tended to fall near one another. Four rapidly developing tastes were elevated in the space: maltose and sorbitol (which are syrupy), monellin (which also has a long sweet aftertaste), and d-tryptophan (which has a relatively long bitter aftertaste). There are some trends in structural similarities among stimuli which fall close together in the space. However, no definitive relationship between molecular structure and quality was found. F o r example, the proteins monellin and thaumatin, as well as the dipeptide aspartame, fall on one side of the space: however, the amino acid d-tryptophan falls on the other side of the space. Ca cyclamate and aspartame were the two "artificial" sweeteners found to taste most like the sugars. Equating intensities proved to be a very difficult and arduous task, revealing two important characteristics of sweet-tasting compounds. First, sweetness ratings were not found to be directly related to a " s w e e t " component, but rather to be a complex judgment which weights other aspects of the stimuli as well. F o r example, strong concentrations of acetosulfam were rated less sweet than weak concentrations because the intensity of the bitter component in the strong concentration diminished the perceived sweetness. There was extremely wide variation in the intensity ratings for maltose depending on how salient subjects found its syrupy texture and off-color in overall intensity.
Initially, the experimenters had desired to adjust the concentrations such that the stimuli would be equally intense with regard to " s w e e t n e s s . " However, subjects were unable to perform this task because they found it difficult to extract a common quality called " s w e e t n e s s " from the other qualitative and temporal complexities of the stimuli. For this reason, the final concentrations were determined such that the geometric means of the individual intensity ratings, when overall impact as well as sweetness was considered, were approximately equal. In addition, the patterns of intensity ratings on the sweeteners were highly variable over subjects. Faurion and Macleod [13] also found that the patterns of suprathreshold intensity measurements as well as threshold values were variable over subjects. In their data, there was a tendency, however, for patterns of moneUin and thaumatin to be related: fructose and glucose were somewhat related: and the amino acid d-leucine fell separate from the rest of the stimuli. This, interestingly, is consistent with the qualitative spatial arrangement in Fig. 2, where monellin and thaumatin fall close to one another: fructose and glucose are similar qualitatively: and the amino acid d-tryptophan falls apart from the rest of the stimuli. The variability in intensity ratings suggests that the sweet taste may be mediated by several peripheral receptor mechanisms. To support this hypothesis, Faurion and Macleod [13] pointed out that, although pronase E and semi-alkaline protease (Hiji [16]), and gymnemic acid (Bartoshuk et al. [1] and Diamant et al. [ l i d appear to selectively inhibit the sweet taste, the level of inhibition is not uniform across all sweeteners. Hiji's data indicated that pronase E and semialkaline protease partially depressed whole chorda tympani responses to glycine and alanine in rat while fully suppressing responses to glucose, fructose, sorbitol and saccharin. Zawalich [46] found that alloxan selectively depressed the integrated neural responses to sugars with no effect on artificial sweeteners, such as sodium saccharin. In addition, in psychophysical experiments in man, McBurney [271 found that sweeteners do not equally cross-adapt. If more than one kind of receptor site mediates the sweet taste, this may explain the comments made by numerous subjects that sweetness is qualitatively different among the stimuli tested apart from bitter, textural, or temporal differences. The fact that it is so difficult to relate structural features of the molecules to the spatial configuration in Fig. 2 may be due to the fact that there are several peripheral receptor mechanisms for the sweet taste with stimuli using the same receptor sites falling near one another in the space. Preliminary cross-adaptation studies by the senior author indicate that stimuli falling close to one another in the space in Fig. 2 cross-adapt more than stimuli located distant from one another. Application of multidimensional scaling to a portion of the multidimensional sweetener space utilizing analogs of aspartame [26] or chlorosucroses [20], for example, could possibly shed more light on the relationship of sweetness to chemical structure for a particular type of receptor. Enlarging the number of sweeteners arranged by multidimensional scaling may enable us to help determine how many receptor mechanisms mediate sweetness.
DIFFERENCES
AMONG SWEETENERS
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