Gluconeogenesis and the Maintenance
of Blood Glucose During Fasting
1. Describe the pathway for gluconeogenesis
- Control Enzymes:
- Tissues of interest:
2. There are three irreversible reactions in glycolysis, name the substrates and products of those reactions and the enzymes that catalyze them. There are four enzymes unique to gluconeogenesis that catalyze reactions that circumvent the irreversible reactions of glycolysis. Name the enzymes, reactants and products.
3. What are the sources of the gluconeogenic precursors and how are they converted into pyruvate, TCA cycle intermediates, or dihydroxyacetone phosphate?
4. Name the enzymes that convert lactate and alanine to pyruvate and that convert glycerol to dihydroxyacetone phosphate.
5. Explain why ingestion of large quantities of alcohol inhibits gluconeogenesis.
6. Most of our diet contains even numbered fatty acids. Can we form glucose from them? Some of our diet contains odd numbered fatty acids. Can we form glucose from them? How?
7. Describe the pathway for the conversion of pyruvate to phosphoenolpyruvate by naming the intermediates, the compartments, the control enzyme, and the allosteric regulator for the control enzyme. Include the terms pyruvate carboxylase, biotin, ATP, oxaloacetate, acetyl CoA, malate dehydrogenase, NADH, malate, phosphoenolpyruvate carboxykinase, GTP. Ignore aspartate.
8. Name the phosphatases that convert fructose-1,6-bisphosphate to glucose in liver.
9. How does fasting, stress, exercise, or a high protein meal affect the level of substrates for gluconeogenesis?
10. Explain the control of the conversion of pyruvate to phosphoenolpyruvate during gluconeogenesis. Name two enzymes in the pathway, a positive allosteric modifier activates one and one is activated principally by induction. Why isn't phosphoenolpyruvate converted to pyruvate and why isn't pyruvate converted to acetyl CoA during gluconeogenesis? Include the terms acetyl CoA, cyclic-AMP, phosphorylation, NADH, and, again, acetyl CoA in your answer.
11. Explain the activation of the fructose-1,6-bisphosphatase during gluconeogenesis. What prevents the reverse reaction and a futile cycle from occurring?
12. Name the enzyme that converts glucose-6-phosphate to glucose in liver.
13. Compare the energy used in the conversion of two moles of pyruvate to glucose with the energy generated during glycolysis when one mole of glucose is converted to two moles of pyruvate.
14. How is the energy used for gluconeogenesis obtained?
15. What are the major factors that regulate blood glucose?
16. What happens to the blood concentrations of insulin and glucagon and the insulin/glucagon ratio following ingestion of a high carbohydrate meal, a high protein meal, and a normal meal?
17. What is the fate of glucose in the liver following a normal or high carbohydrate meal? How does the increased blood glucose and the increased insulin/glucagon ratio affect the cAMP cascade, the activity of protein phosphatase, glycogen synthesis, glycogenolysis, glycolysis, gluconeogenesis, glycerol-3-phosphate synthesis, fatty acid synthesis, triacylglycerol synthesis, and VLDL synthesis?
18. In some tissues, an increase in blood insulin will substantially increase the glucose transporters in the cell membrane and the transport of glucose into cells. Which of these tissues react in this manner and which do not: muscle, adipose tissue, brain, and liver?
19. What is the affect of increased blood insulin upon glycogen synthesis in muscle?
20. What are the affects of increased insulin upon glycerol-3-phosphate synthesis, fatty acid uptake from VLDLs, and triacylglycerol synthesis in adipose tissues?
21. As blood glucose decreases and the insulin to glucagon ratio drops, the cyclic AMP cascade causes a change in the activities of the enzymes concerned with glycogen metabolism so that glucose is released into the blood. Be able to name all the intermediates in the proper order in this pathway. Use the terms glucagon receptor, G-protein, adenyl cyclase, cAMP, protein kinase A, regulatory subunits, catalytic subunits, phosphorylase kinase, phosphorylase, glycogen synthase, glucose-1-P, glucose-6-P, glucose-6-phosphatase, and glucose.
22. As blood glucose decreases and the insulin to glucagon ratio drops, the cyclic AMP cascade causes a change in the activities of the enzymes concerned with gluconeogenesis and glycolysis so that glucose is released into the blood. From the time when glucagon binds it's receptor, be able to name all the intermediates in the proper order in the pathway that activates fructose-1,6-bisphosphatase and inhibits phosphofructokinase-1 and pyruvate kinase. Use the terms glucagon receptor, G-protein, adenyl cyclase, cAMP, protein kinase A, regulatory subunits, catalytic subunits, phosphofructokinase-2/fructose-2,6-bisphosphatase, and fructose-2,6-bisphosphate.
23. As blood glucose decreases and the insulin to glucagon ratio drops, the cyclic AMP cascade causes an increase in lipolysis in adipose tissue. What are the products of lipolysis and how do liver and muscle use them? Include the terms fatty acids, glycerol, gluconeogenesis, energy, and ketone bodies.
24. Between 3 days and 6 weeks of starvation, what happens to the blood concentrations of glucose, free fatty acids, and ketone bodies? What happens to the total utilization of glucose by the body? What happens to the total utilization of fat by the body? Between 3 days and 6 weeks of starvation, what happens to total urinary nitrogen excretion? Note that total urinary nitrogen is at least 80% urea. Explain this change in urea excretion.
25. Be able to state the major source of glucose (ingested, glycogenolysis, or gluconeogenesis) used by a sedentary person following ingestion of a meal. For example, at l hour, 4 hours, 16 hours, and 30 hours. Assume that the subject was sedentary. What would happen to this timetable if the person were running a marathon?
26. What values does the American Diabetes Association use to define diabetes and pre-diabetes from fasting blood glucose? Error in lecture. Correct answer: Normal fasting blood glucose is below 100 mg/dl. A person with pre-diabetes has a fasting blood glucose level between 100 and 125 mg/dl.
27. Concerning Al Martini who has not eaten and has been drinking heavily for the past three days, explain his hypoglycemia in terms of the reactions that are inhibited and why they are inhibited?
28. Concerning Emma Wheezer: What were the effects of dexamethasone that contributed to muscle weakness and hyperglycemia?
29. What is the major glucocorticoid in humans?
30. Concerning Di Abietes, who suffers from Type I diabetes and is in a coma because she took an overdose of insulin 13 hours ago,
- (1) how can you tell from her rate and depth of respiration that she is not suffering from diabetic ketoacidosis?
- (2) what had happened to the normal pathways for energy production in the fasting state? Include fatty acid mobilization, ketone body synthesis, glycogenolysis, and gluconeogenesis.
31. Concerning Di Abietes, who suffers from Type I diabetes, what is the pathogenesis of her disease? What is the pathogenesis of Type 2 diabetes?
32. Concerning Otto Shape who is now in shape and jogs in the morning before breakfast. How does he maintain his blood glucose levels? Does increased blood epinephrine help this process?
33. Understand the meaning of each of the keywords.
Keywords: Acetyl CoA, adenyl cyclase, alanine aminotransferase, amino acids, ATP, biotin, cAMP, catalytic subunits, cortisol, covalent modification, energy, epinephrine, exercise, fasting, fatty acids, feed forward activation, fructose-6-phosphate, fructose-1,6-bisphosphatase,, fructose-1,6-bisphosphate, fructose-2,6-bisphosphate, G-protein, glucagon, glucagon receptor, gluconeogenesis, glucose , glucose-6-phosphatase, glucose-1-P, glucose-6-P, glycerol, glycerol kinase, glycerol-3-phosphate dehydrogenase, glycogen synthase, GTP, high protein diet, induction, insulin, insulin resistance, impaired glucose tolerance, ketone bodies, lactate, lactate dehydrogenase, lipolysis, malate, malate dehydrogenase, mitochondria, muscle degradation, NADH, oxaloacetate, phosphoenolpyruvate, phosphoenolpyruvate carboxykinase, phosphofructokinase-1, phosphofructokinase-2/fructose-2,6-bisphosphatase, phosphorylase, phosphorylase kinase, protein, protein kinase A, pyruvate, pyruvate carboxylase, pyruvate dehydrogenase, pyruvate kinase, regulatory subunits, starvation, stress
Examine questions in Chapter 31.
Examine questions 1, 2, 3, 4, and 5 at the end of Chapter 31.
Practice Questions for Chapter 31 Objectives
Third Edition Figure Map
Definition of Diabetes and Pre-Diabetes
Reference: Marks' Basic Medical Biochemistry: A Clinical Approach, 2nd Edition, 2004, Williams and Wilkins (ISBN: 0-7817-2145-8) by Colleen M. Smith PhD, Allan D. Marks MD, and Michael A. Lieberman PhD