168 SECTIONAL ADDRESSED. 



example being tliab of isomaltose from glucose by Croft Hill — has so 

 far been seldom achieved. Barbour in the experiment just referred to 

 was unable to demonstrate any synthesis of glycogen from the trisaccharide 

 produced by the muscle enzyme even in highly concentrated solutions. 



This failure to obtain evidence of the synthesis of glycogen from the 

 products of its hydrolysis makes it legitimate to consider whether we are 

 right in adopting the orthodox view that the synthesis of glycogen from 

 glucose in the living cell is brought about by a reversal of action of the 

 enzyme or enzymes which hydrolyse it. 



Besides the facts about the constitution of glycogen and the nature of 

 its hydrolytic products that have already been mentioned, there are others 

 which merit consideration in any discussion of its mode of synthesis in the 

 body. When an animal is fed liberally with glucose or fructose it converts 

 a part of them into glycogen in the liver. The evidence for this is indubit- 

 able. It implies, therefore, either a conversion of fructose into glucose 

 before the condensation to glycogen occurs or a conversion of both into 

 some common form of hexose which then undergoes the condensation. 

 Further, there is a considerable amount of accredited evidence that many 

 substances not belonging to the sugar group can be converted into glucose 

 in the animal body. Such substances therefore, must be regarded as 

 potential glycogen formers. Several amino-acids such as alanine, glutamic 

 acid, aspartic acid, glycine and serine come into this category. Then it is 

 well known that glycogen can be formed from the trioses glyceric aldehyde 

 and dihydroxyacetone as well as from methyl glyoxal and lactic acid, 

 which are easily derived from them in vitro. In addition, glycerol and 

 glycolaldehyde can give rise to glucose in the diabetic animal though the 

 evidence in favour of the latter is not very convincing. It is easy to 

 understand from the work of Emil Fischer on the synthesis of hexoses 

 from glycerose how glycerol and the two trioses could give rise to a hexose 

 in the body. It is also possible that methyl glyoxal by condensation and 

 hydration could be converted into a hexose and that lactic acid, which has 

 been shown by Dakin and Dudley to be capable of conversion into methyl 

 glyoxal in vitro, could also undergo the same change. But the production 

 of glucose from amino-acids is not explicable so easily except in the case 

 of alanine and perhaps aspartic acid, and we must assume that in the 

 process of catabolism which they undergo intermediate substances are 

 produced which can. condense to a hexose. Our knowledge of the metabolic 

 changes which the amino-acids undergo suffices in some instances to offer 

 a reasonable explanation of this on chemical grounds, but not in all. 

 Whatever these processes may be which eventually result in the production 

 of a hexose from such diverse substances, the most remarkable thing about 

 them to my mind is that the hexose is always d-glucose. We have no 

 satisfactory explanation for this striking stereochemical performance, but 

 the facts suggest two possibilities. Either the condensation of the two — ■ 

 or three — carbon units to a hexose is brought about under such specific 

 conditions of strain that only the (Z-glucose configuration can result, much 

 as coins must be minted in a definite mould to become currency, or the 

 hexose produced by these various condensations is a labile form which 

 condenses to glycogen and is in turn hydrolysed to glucose. But to 

 produce this hypothetical labile form of hexose or to bring about its 



