CHEMICAL STRUCTURE AND STIMULATION BY 

 CARBOHYDRATES* 



David R. Evans 



Department of Biology, Johns Hopkins University, Baltimore 18, Maryland 



ABSTRACT 



Based on considerations of the configurational and conformational structure of 

 polyols and experimental evidence, it is proposed that the polyols which stimulate 

 taste receptors of the blowfly combine with two or more distinct receptor sites, each 

 with unique structural requirements, and that these sites are associated with the same 

 receptor cell. The stimulating elTectiveness of a series of derivatives of D-glucose 

 are assessed to determine the structural requirements for stimulation by that molecule. 

 It is tentatively concluded that only the hydroxyl groups on C3 and C4 of the molecule 

 combine with the receptor site and that additional specificity is conferred on the 

 reaction by steric hindrance due to substituents not otherwise involved. Some 

 evidence is discussed in relation to the mechanism of stimulation by polyols. It 

 would appear that polyols combine with receptor sites through weak, physical forces 

 although the reaction has a high degree of specificity. How the reaction produces 

 depolarization of the receptor is posed as a unique and challenging problem of 



neurophysiology. 



Ingestive behavior of animals is frequently elicited upon stimulation of 

 their taste receptors by various carbohydrates. The chemical species which 

 evoke a *' sweet " taste for mammals, and especially humans, have been the 

 subject of much research (cf. Pfaffman, 1959). There are a number of 

 puzzling facts about the sweet taste, probably the most puzzling of which 

 is the wide array of chemical species that elicit it, while at the same time 

 there is a rather high degree of specificity sometimes toward the structure 

 of chemicals of the same general type. Many carbohydrates (e.g. glycols, 

 glucose, sucrose, and glycogen), L-amino acids (not d), certain synthetic 

 aromatic compounds (e.g. saccharin), lead acetate, and beryllium salts, all 

 are effective. Furthermore, the same inhibitor for the sweet taste (gym- 

 nemic acid) blocks stimulation by radically different chemicals (sucrose and 

 saccharin : Warren and Pfaffman, 1959). There are also complexities 

 relating to the frequent close association of different taste qualities (sweet 

 and bitter), both in terms of chemical structure and after-tastes. Gym- 

 nemic acid inhibits both sweet and bitter, while the salt and acid qualities 

 are unaffected. And synthetic sweeteners, such as saccharin, often has a 

 bitter after-taste. The last thorough attempt to relate sweetness to chemical 



*Supported by grant number E-2358 from the U.S. Public Health Service. 



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