Chapter 25

Match the terms on the left with the descriptions on the right. (a) UDP-glucose _____ (b) UDP-glucose pyrophosphorylase _____ (c) Glycogen synthase _____ (d) Glycogenin _____ (e) Branching enzyme _____ (f) Glucose 6 -phosphate _____ (g) Glycogen synthase kinase _____ (h) Protein phosphatase 1 _____ (i) Insulin _____ (j) Glycogen phosphorylase \(a\) _____ 1\. Glucose 1 -phosphate is one of its substrates. 2\. Potent activator of glycogen synthase \(b\) 3\. Glucose sensor in the liver. 4\. Activated substrate for glycogen synthesis. 5\. Synthesizes \(\alpha-1,4\) linkages between glucose molecules. 6\. Leads to the inactivation of glycogen synthase kinase. 7\. Synthesizes \(\alpha-1,6\) linkages between glucose molecules. 8\. Catalyzes the formation of glycogen synthase \(b\). 9\. Catalyzes the formation of glycogen synthase \(a\). 10\. Synthesizes the primer for glycogen synthesis.

What enzymes are required for the synthesis of a glycogen particle starting from glucose 6 -phosphate?

UDP-glucose is the activated precursor for glycogen synthesis, but ultimately ATP is the power behind glycogen synthesis. Prove it by showing the reactions required to convert glucose 6 -phosphate into a unit of glycogen with the concomitant regeneration of UTP.

The following reaction accounts for the synthesis of UDP-glucose. This reaction is readily reversible. How is it made irreversible in vivo? $$\text { Glucose 1-phosphate }+\text { UTP } \rightleftharpoons \text { UDP-glucose }+\mathrm{PP}_{\mathrm{i}}$$

Why does activation of the phosphorylated \(b\) form of glycogen synthase by high concentrations of glucose 6 -phosphate make good biochemical sense?

Describe the separate roles of glycogenin and glycogen synthase in glycogen synthesis.

The complete oxidation of glucose 6 -phosphate derived from free glucose yields 30 molecules ATP, whereas the complete oxidation of glucose 6-phosphate derived from glycogen yields 31 molecules of ATP. Account for this difference.

Phosphoglucomutase is crucial for glycogen breakdown as well as for glycogen synthesis. Explain the role of this enzyme in each of the two processes.

Write a balanced equation showing the effect of the simultaneous activation of glycogen phosphorylase and glycogen synthase. Include the reactions catalyzed by phosphoglucomutase and UDP-glucose pyrophosphorylase.

Suggest an explanation for the fact that the amount of glycogen in type I glycogen-storage disease (von Gierke disease) is increased.

Briefly predict the major consequences of each of the following mutations affecting glycogen utilization. (a) Loss of GTPase activity of the G-protein \(\alpha\) subunit. (b) Loss of phosphodiesterase activity.

Von Gierke disease is frequently the result of a defect in glucose 6 -phosphatase. Suggest another mutation in glucose metabolism that causes symptoms similar to those of von Gierke disease.

UDP-glucose is the activated form of glucose used in glycogen synthesis. However, we have already met other similar activated forms of carbohydrate in our consideration of metabolism. Where else have we seen UDP-carbohydrate?

In human liver extracts, the catalytic activity of glycogenin was detectable only after treatment with \(\alpha\) -amylase, an enzyme that hydrolyzes \(\alpha-1,4\) -glucosidic bonds. Why was \(\alpha\) -amylase necessary to reveal the glycogenin activity?

A sample of glycogen from a patient with liver disease is incubated with orthophosphate, phosphorylase, the transferase, and the debranching enzyme \((\alpha-1,6-\text { glucosidase }) .\) The ratio of glucose 1 -phosphate to glucose formed in this mixture is \(100 .\) What is the most likely enzymatic deficiency in this patient?