Chapter 17

They are everywhere. What energetic barrier prevents glycolysis from simply running in reverse to synthesize glucose? What is the energetic cost of overcoming this barrier?

What reactions of glycolysis are not reversible under intracellular conditions? How are these reactions bypassed in gluconeogenesis?

Avidin, a 70 -kDa protein in egg white, has very high affinity for biotin. In fact, it is a highly specific inhibitor of biotin enzymes. Which of the following conversions would be blocked by the addition of avidin to a cell homogenate? (a) Glucose \(\rightarrow\) pyruvate (b) Pyruvate \(\rightarrow\) glucose (c) Oxaloacetate \(\rightarrow\) glucose (d) Malate \(\rightarrow\) oxaloacetate (e) Pyruvate \(\rightarrow\) oxaloacetate (f) Glyceraldehyde 3 -phosphate \(\rightarrow\) fructose 1,6 -bisphosphate

Gluconeogenesis takes place during intense exercise, which seems counterintuitive. Why would an organism synthesize glucose and, at the same time, use glucose to generate energy?

Liver is primarily a gluconeogenic tissue, whereas muscle is primarily glycolytic. Why does this division of labor make good physiological sense?

What would be the effect on an organism's ability to use glucose as an energy source if a mutation inactivated glucose 6 -phosphatase in the liver?

Why does the lack of glucose 6 -phosphatase activity in the brain and muscle make good physiological sense?

Compare the roles of lactate dehydrogenase in gluconeogenesis and in lactic acid fermentation.

In starvation, protein degradation takes place in muscle. Explain how this degradation might affect gluconeogenesis in the liver.

What are the two potential substrate cycles in the glycolytic and gluconeogenic pathways?

What is the regulatory role for the substrate cycles in glycolysis and gluconeogenesis?

How might enzymes that remove amino groups from alanine and aspartate contribute to gluconeogenesis?

Predict the effect of each of the following mutations on the pace of glycolysis in liver cells. (a) Loss of the allosteric site for ATP in phosphofructokinase (b) Loss of the binding site for citrate in phosphofructokinase (c) Loss of the phosphatase domain of the bifunctional enzyme that controls the level of fructose \(2,6-\) bisphosphate (d) Loss of the binding site for fructose \(1,6-\) bisphosphate in pyruvate kinase

Glycerol is released when lipids are used as a fuel. The released glycerol can be salvaged and can be used in glycolysis or gluconeogenesis in the liver. Show the reactions that are required for this conversion.

Yeast are facultative anaerobes-they can grow in the absence of oxygen (anaerobically) using alcoholic fermentation or in the presence of oxygen (aerobically) using cellular respiration. Interestingly, yeast cannot live anaerobically using glycerol as their only fuel source. Explain why yeast cannot survive metabolizing glycerol anaerobically.

Why is the conversion of lactic acid from the blood into glucose in the liver in an organism's best interest?

What are the likely consequences of a genetic disorder rendering fructose 1,6 -bispho=sphatase in the liver less sensitive to regulation by fructose \(-2,6-\) bisphosphate?

If cells synthesizing glucose from lactate are exposed to \(\mathrm{CO}_{2}\) labeled with \(^{14} \mathrm{C}\), what will be the distribution of label in the newly synthesized glucose?

Compare the stoichiometries of glycolysis and gluconeogenesis. Recall that the input of one ATP equivalent changes the equilibrium constant of a reaction by a factor of about \(10^{8}(\mathrm{p} .262) .\) By what factor do the additional high-phosphoryl-transfer compounds alter the equilibrium constant of gluconeogenesis?