1.— PHYSIOLOGY. 169 



condensation to glycogen would probably require such conditions of speci- 

 ficity that this second hypothesis seems unnecessary. 



The view that any substance that produces glucose in the body may 

 also give rise to glycogen is supported .by good experimental evidence. 

 Several of the glucose-formers that have been already mentioned are able 

 to produce glycogen in the isolated, perfused liver, particularly in the liver 

 of the tortoise. But the difficulties of this kind of experiment are con- 

 siderable and the conditions for success are not completely understood. 

 It is, however, essential that the liver cells be alive and adequately supplied 

 with oxygen. It has also been demonstrated that insulin plays some 

 part in enabling this synthesis to be brought about ; but exactly how it 

 enters into the process is not known. 



Much more exact studies of the synthesis of glycogen in the animal cell 

 than are possible with liver have been made with frog's muscle. Fletcher 

 and Hopkins, in their well-known experiments on the production of lactic 

 acid by muscle, showed that in undamaged muscle and in the presence of 

 oxygen the lactic acid which is produced during the contraction process 

 disappears. Meyerhof proved later that the disappearing lactic acid was 

 largely reconverted into glycogen. Assuming that the oxygen which is 

 necessary for this process is used in oxidising a part of the lactic acid, we 

 get the relation that of four parts of lactic acid produced in the muscle, 

 one is oxidised and three are utilised for the resynthesis of glycogen. 

 Under more ideal experimental conditions and using thermal data, Hartree 

 and Hill calculated that the ratio of lactic acid resynthesised to lactic acid 

 oxidised is about four to one. The chemical mechanism of this synthesis 

 is unknown. Under conditions in which muscle produces glycogen from 

 lactic acid, Meyerhof was unable to observe such a synthesis from a series 

 of substances including, among others, glyceric acid, glyceric aldehyde, 

 dihydroxyacetone, alanine, glycollic acid, glycolaldehyde and acetalde- 

 hyde. The only substance discovered to behave like lactic acid was pyruvic 

 acid, and Meyerhof has expressed the view that this is due to its preliminary 

 reduction to lactic acid. We have thus no evidence of the intermediate 

 substances between lactic acid and glycogen in this synthesis. On the 

 other hand, we have the very positive evidence that it occurs only in the 

 presence of oxygen. Although this suggests that a coupled reaction is 

 concerned involving the utilisation for synthesis of energy provided by 

 oxidation, no satisfactory picture of an oxidative reaction of lactic acid 

 which would result in the production of glycogen, water and carbon dioxide 

 has been put forward. 



A consideration of all the data which have been acciimulated regarding 

 the synthesis of glycogen makes it probable that more than the mere 

 reversal of enzyme action is concerned. It is certain that the cells in which 

 it occurs must be supplied with oxygen. Fletcher and Hopkins also showed 

 with muscle that its structure must be maintained and with liver the syn- 

 thesis certainly only takes place in the intact organ. Do not these facts 

 point to the conclusion that it is only the living cell that can bring about 

 this synthesis ? And if this be so, cannot we go further and suggest that 

 the substances from which glycogen are produced or bodies derived from 

 them must first become bound up with, or at some stage form an integral 

 part of the living structure before they are converted into glycogen. The 



