702 METABOLISM 



enzyme glycogenase, which is present, not only in the liver cell, but 

 also in the blood and lymph. It is a difficult matter to explain why 

 glycogen should be able to exist at all in the liver cells in the presence 

 of this powerful enzyme. The following possibilities may be considered: 

 (1) That glycogenase does not really exist in the living liver cells, but 

 .is a postmortem product; (2) that, although present, glycogenase is pre- 

 vented from acting on .the glycogen in the living liver cell on account of 

 the latter being protected from its influence by combination with a 

 sustentacular substance; or (3) that some chemical substance in the liver 

 cell prevents the glycogenase from acting on the glycogen an anti- 

 glycogenase. Since the removal of any one of these inhibiting influ- 

 ences would cause glycogenolysis to become excessive, and so bring 

 about hyperglycemia, it is important, in searching for the possible 

 causes of this condition, to examine the evidence that has been brought 

 forward in support of each of these views. 



Against the first of the above-mentioned possibilities, namely, that glycogenase is a 

 post-mortem product, may be cited the very rapid conversion into glucose that occurs 

 when glycogen is added to living blood, as by injecting some into a vein. On account of 

 the active; glycogenolytic action of blood, it has been suggested that during life glycogen 

 does not become transformed into glucose until after it has been discharged into the 

 blood from the liver cell. When increased sugar must be mobilized, glyeogen passes 

 unchanged, or perhaps as some dextrine, into the blood and lymph of the liver capillaries 

 and lymphatics, the glycogenase of which converts it into glucose, the conversion being 

 so rapid that, by the time the blood has traveled from the liver through the heart 

 and pulmonary vessels to the arteries, all the glycogen has already become transformed 

 into glucose. Postmortem glycogenolysis, according to this view, is due to the opposite 

 occurrence the transference of glycogenase from the blood into the liver cell. Some 

 facts supporting this view are as follows: (1) It has been found that the amount of 

 free glucose in the blood of the vena cava is sometimes less than in that collected simul- 

 taneously from the carotid artery. (2) After giving certain substances, such as phos- 

 phorus or peptone, there is distinct diminution in the amount of glycogen in the liver, 

 accompanied, it is said, by no increase in the amount of glucose in the blood. And 

 (3) if the liver of an animal that has been rendered diabetic by stimulation of the 

 splanchnic nerve or by puncture of the floor of the fourth ventricle is examined micro- 

 scopically, after staining by the carmine method, masses of stained glycogen can be 

 found present in the capillaries (sinusoids) that lie between the liver cells. 



According to the second view, the glycogen is removed from the influence of the in- 

 trahepatic glycogenase on account of its combination with a sustentacular material. 

 By disrupting this combination and thus exposing the glycogen to the action of glyco- 

 genase, glycogenolysis will occur. We may call this the mechanical hypothesis and 

 it deserves serious consideration, for it has been shown that very little postmortem 

 glycogenolysis occurs in the intact liver of frogs in winter, even though at this time 

 the organ contains an excess of glycogen, but becomes marked when the liver is broken 

 down by mechanical means. 



The third view depends on the well-known fact that enzyme activities becomes most 

 markedly altered by slight changes in the chemical nature of the environment in which 

 they act. Diastatic enzymes are particularly susceptible to the reaction (C H ) of their 

 environment, a very slight degree of acidity favoring and a trace of alkalinity mark- 



