Glucose 1-phosphate glycogen synthesis

The mechanism of the ketosis and hyperlipidemia observed in von Gierke s disease is not known, and only tentative explanations can be provided. Several pathways are available for the utilization of glucose-6-phosphate glycogen synthesis, glycolysis, oxidation... 

The breakdown of glycogen to glucose 1-phosphate is catalyzed by phosphorylase. Glycogen synthesis involves a different pathway via uridine diphosphate glucose and glycogen synthase (Figure 18-1). 

A positive AG for this reaction conld also be achieved by a marked decrease in the concentration of glucose 6-phosphate. Why is this not feasible Glucose 6-phosphate is an important metabolic intermediate and is involved in several metabolic pathways (e.g. glycogen synthesis, glycolysis, pentose phosphate pathway). Lowering its concentration by the two orders of magnitude, which would be necessary, would markedly decrease the rates at which these important pathways could proceed. 

Figure 6.19 Regulation of the synthesis of glycogen from glucose in liver and muscle. Insulin is the major factor stimulating glycogen synthesis in muscle it increases glucose transport into the muscle and the activity of glycogen synthase, activity which is also activated by glucose 6-phosphate but inhibited by glycogen. The latter represents a feedback mechanism and the former a feedforward. The mechanism by which glycogen inhibits the activity is not known. The mechanism for the insulin effect is discussed in Chapter 12.

The glucose concentration is the major factor regulating glycogen synthesis in liver. Glucose activates glucokinase directly as a substrate and indirectly via an increase in the concentration of fructose 6-phosphate. It also activates glycogen synthase but it inhibits glycogen phosphorylase (see text). 

Source of glucose 6-phosphate for glycogen synthesis in the liver... 

One is the glucose that is absorbed from the intestine and enters the blood in the hepatic portal vein from where some of it is taken np by the Uver and phosphorylated to form glncose 6-phosphate, which then stimulates the formation of glycogen (for discnssion of regulation of this process, see below). This is known as the direct pathway for glycogen synthesis. 

Figure 12.18 Sites at which insulin stimulates glycogen synthesis in muscle. An increase in the blood glucose level, after a meal, increases secretion of insulin from the p-cells in the Islets of Langerhans. Insulin increases the transport of glucose into the muscle fibre and the activity of glycogen synthase (Chapter 6). The result is that insulin increases the rate of glycogen synthesis without marked changes in concentrations of glucose 6-phos-phate, glucose 1-phosphate or UDP-glucose in the liver.

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