CHEMICAL STRUCTURE AND STIMULATION 



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sugar depends upon nonbonded interactions among its substituents : 

 especially the ring oxygen atom, the hydroxyl groups, and the carbinol 

 group of aldohexopyranoses. Of the aldohexoses, only d- and L-glucose 

 are capable of having all such substituents in the equatorial position (CI 

 and IC conformations respectively — Fig. 1) where they are most stable. 



CH2OH 



CH2OH 



H0^_ 



OH 



OH 



Fig. I. />-D-glucopyranose in the IC and CI conformations. 



Hence, both are present in solution (or in crystals) almost entirely in a chair 

 conformation as the aldopyranose and are more stabilized in this form than 

 are other aldohexoses. As a consequence also, derivatives of most kinds 

 do not change the conformation. Based on these considerations, the struc- 

 ture of D-glucose that was responsible for stimulation was assessed by 

 comparing the effectiveness of a series of its derivatives (Table 1). In that 

 table, cpds 1-23 are relevant to the point at hand. Compounds 1-8, 10, 

 and 13-20 have 6-membered rings in the CI conformation. Compounds 

 9 and 11 have 5-membered rings which are planar. Compound 12 can be 

 considered largely comparable to glucopyranose by appropriate designation 

 of the first carbon atom. Compounds 21-23 are disaccharides of glucose to 

 which more complicated conformational considerations must be applied. 



In several biological systems, conformational analysis has proven essen- 

 tial for an understanding of reaction mechanisms. 



LeFavre and Marshall (1958) have given evidence that transport of 

 sugars by the facilitated diffusion system of the red blood cell has simply 

 the requirement that the sugar be in the CI conformation. The more stable 

 a sugar is in that form, the greater its affinity for the " carrier " system. 

 Hence, D-glucose has about the greatest affinity, and L-glucose the least. 

 Since sugars which are most stable in the IC conformation are apparently 

 never utilized by organisms, the authors further suggest that enzymes that 

 act on carbohydrates have foremost a requirement for the CI conformation 

 like the red cell system, but that they then are differentiated by their addi- 

 tional configurational requirements. This generalization does not apply 

 to stimulation of the sugar receptors of the fly since sugars in the IC con- 

 formation are effective stimuli (L-fucose and L-xylose : Hassett et al., 

 1950). 



