CHEMICAL STRUCTURE AND STIMULATION 173 



If the Structural requirements are as proposed, it might be expected that 

 linear polyols would stimulate ; but Dethier (1955) reported that mannitol 

 and glucitol did not. Some small fraction of vicinal hydroxy! groups, how- 

 ever, ought to be in the proper orientation in solution at any given time. 

 When flies were starved longer than Dethier's, until they were maximally 

 sensitive, all would respond to saturated solutions of the two hexitols. 

 And further, ingestion of the solutions, which depends on continual stimu- 

 lation of the sugar receptor (Dethier et aL, 1956), was supported for 1-2 

 min. While taste thresholds measure the inital response of the sugar re- 

 ceptor (i.e. for ca. 100 msec), feeding duration is a measure of the con- 

 tinuing response. Since the hexitols are free to rotate about single C — C 

 bonds and all conformations are potentially rapidly interconvertible, the 

 receptor may bind one form, causing conversion of others in the solution 

 to more of that form. 



Possible Spatial Relationships of Combining Sites 



The remaining selected compounds listed in Table 1 may signify some- 

 thing about the size and/or spatial distribution of combining sites. Since 

 maltose is among the most effective sugars (33 X more effective than glu- 

 cose), it may be that the combining sites are larger than one hexose unit, 

 or that sites are spatially juxtaposed. Recent evidence suggests that the 

 non-reducing hexose unit of maltose does not have the CI conformation 

 (Reeves, 1959, pp. 19-20) and the C4-OH of the reducing moiety is in- 

 volved in the glucosidic link ; consequently, the great effectiveness of 

 maltose most likely is not owing to the juxtaposition of two similar glucose 

 binding sites. Another y. disaccharide of glucose, trehalose, is only about 

 as effective as glucose alone ; while another disaccharide of glucose with the 

 /y configuration (cellobiose) is only weakly effective. As was pointed out 

 before, glucose and fructose synergize in mixtures (Dethier et al., 1956 and 

 Table 1). Sucrose is somewhat less effective than such mixtures and much 

 less so than fructose alone. A similar disaccharide of glucose and fructose 

 (turanose) but linked at the C3 position of fructose is about as effective as 

 sucrose. The trisaccharide, melezitose, which corresponds to either 

 sucrose or turanose with a glucose residue linked to one or the other end is 

 much less effective than either of the disaccharides. Very likely these and 

 other similar results reflect the size and arrangement of combining sites on 

 the receptor and the conformation of the molecules. 



Mechanism of Stimulation 



Dethier (1955) has given evidence that stimulation by sugars involves 

 a physical rather than a chemical reaction, but, of course, a highly specific 

 one. His argument was based largely on the lack of effect of various meta- 

 bolic inhibitors on sugar stimulation (e.g. azide, fluoride, cyanide, iodo- 



