DEWITT STETTEN, JR. 



source of blood glucose. The immediate hepatic source of 

 glucose is from the hydrolysis of glucose-6-phosphate in the 

 presence of a specific glucose-6-phosphatase. Glucose-6-phos- 

 phate arises in liver from various sources, and among these are 

 glycogen, via glucose- 1 -phosphate, and such noncarbohydrate 

 compounds as are capable of contributing organic fragments to 

 the several intermediates of the glycolytic sequence and the 

 citric acid cycle. These latter contributions derive ultimately 

 from the glycogenic amino acids, glycerol, and other compounds, 

 and the over-all process under consideration is termed glyconeo- 

 genesis. 



Of the disease processes which influence the generation of 

 glucose in the liver, the best defined is glycogen storage disease 

 (von Gierke). In an elegant analysis of these patients (5), it has 

 been shown that in many instances the defect is attributable 

 simply to a relative or absolute deficiency of glucose-6-phospha- 

 tase activity in the liver. Such an abnormality makes the liver, 

 like normal muscle, incapable of contributing significant amounts 

 of glucose to the blood, but in no wise interferes with the steps of 

 glycogenesis. Other patients suffering from glycogen storage 

 disease exhibit normal glucose-6-phosphatase activity but 

 appear to deposit glycogen which deviates markedly from 

 normal liver glycogen in its branching pattern. Such glycogen 

 seems, in some cases, to be less readily degraded by the com- 

 bined action of phosphorylase and amylo-l,6-glucosidase. A 

 consequence of either type of glycogen storage disease is a failure 

 to elicit the usual hyperglycemia in response to administered 

 epinephrine. 



Recent evidence indicates that a mode of action of epi- 

 nephrine, as well as of glucagon, is to favor the conversion of 

 inactive phosphorylase into active phosphorylase (21). Whereas 

 this finding, is, of itself, not a complete explanation of the mode 

 of action of these agents, it is highly suggestive that these stimu- 

 lants of glycogenolysis operate at the initial steps of glycogen 

 breakdown. The failure of the blood glucose to rise in response 

 to epinephrine in von Gierke's disease is best explained by the 



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