GLYCOSIDASES 415 



the pentose-P pathway. Sahasrabudhe et al. (1960) in looking for carcino- 

 static analogs found that thiophene-2,5-dicarboxylate, which might be con- 

 sidered as an analog of substances such as ribose-5-P, inhibits the formation 

 of C^^Og from glucose- 1-C^* and glucose-6-C^'* around 43% (concentration 

 unspecified) in tumor tissue, and suppresses the growth in vivo of rat sar- 

 coma. No evidence was given as to the site of action and so the assumption 

 is tenuous, but the concept of using heterocyclic substances analogous to 

 the furanose and pyranose structures may be important. 



GLYCOSIDASES 



This large group of enzymes hydrolyzing the glycosidic bonds of simple 

 glycosides, oligosaccharides, and polysaccharides has been studied for many 

 years and it is not surprising that numerous instances of analog inhibition 

 have been observed. Most of the reports, although important in themselves, 

 do not lend themselves to interpretations on the molecular level; some of 

 the data have been briefly summarized in Table 2-22. Most of the inhibi- 

 tions are relatively weak but a few could definitely be significant in meta- 

 bolic regulation. The a, (3 configuration of the inhibitor is seen to be im- 

 portant in some instances. However, the enzymes are seldom completely 

 specific for the a- or /?-forms and the affinities often diff"er very little, as 

 with maltose transglucosylase (amylomaltase) from E. coli where (see ac- 

 companying tabulation) the binding difference between the u- and /5-glu- 



cosides is 0.14-0.68 kcal/mole (Wiesmeyer and Cohn, 1960). It appears that 

 the hydroxyl groups on C-2, C-4, and C-6 of ring A are involved in the 



CH,OH CH,OH 



-Ott XT J O 



ring A 



