Gluconeogenesis Lecture Review

Flashcards covering key concepts of gluconeogenesis, its purpose, localization, regulation, precursors, and clinical implications, including its interaction with ethanol metabolism and exercise physiology.

What is the overall purpose of gluconeogenesis?

To synthesize glucose de novo from non-carbohydrate precursors to maintain blood glucose levels.

Which tissues require a continuous supply of glucose as a primary energy source?

Mature RBCs, brain, kidney medulla, lens, cornea, testes, and muscle during exercise.

When does gluconeogenesis primarily occur?

When the levels of glucose and glycogen stores are low.

Where does most of the gluconeogenesis take place in the body?

Approximately 90% takes place in the liver. The remaining 10% occurs in the kidneys and intestinal epithelial cells (increasing to 40% in kidneys during prolonged fasting).

Name some non-carbohydrate precursors that can be used for glucose synthesis during gluconeogenesis.

Pyruvate, glycerol, lactate, and glucogenic amino acids.

Which two common amino acids are exceptions and are not glucogenic?

Leucine and Lysine.

What role do ketone bodies play during prolonged fasting?

They are products of beta-oxidation of fatty acids and can be used as an energy source by the brain, heart, and other tissues.

Name the four key enzymes involved in gluconeogenesis that bypass irreversible steps of glycolysis.

Pyruvate Carboxylase, PEP Carboxykinase, Fructose 1,6-Bisphosphatase, and Glucose 6-Phosphatase.

How is Pyruvate Carboxylase allosterically regulated?

It is positively regulated by high levels of Acetyl-CoA and negatively regulated by low levels of Acetyl-CoA.

How does glucagon affect Pyruvate Kinase activity in gluconeogenesis?

Glucagon activates protein kinase A, which phosphorylates and inactivates Pyruvate Kinase, thereby inhibiting glycolysis and favoring gluconeogenesis.

Which enzyme is responsible for bypassing the irreversible PFK1 step in glycolysis during gluconeogenesis?

Fructose 1,6-bisphosphatase.

Describe the Cori Cycle.

It is a metabolic pathway where lactate produced by muscles during anaerobic exercise is transported to the liver, converted to pyruvate and then to glucose via gluconeogenesis, and the glucose is returned to the muscles.

How does glycerol enter the gluconeogenesis pathway?

Glycerol is converted to Glycerol 3-Phosphate (Gro3P), which is then oxidized to Dihydroxyacetone Phosphate (DHAP) and enters the pathway.

How does ethanol metabolism impair gluconeogenesis?

Ethanol metabolism generates a large amount of NADH, which shifts the equilibrium of several reactions, preventing the conversion of lactate to pyruvate, malate to oxaloacetate, and glyceraldehyde 3-P to DHAP. This can lead to hypoglycemia and lactic acidosis.

What are the common clinical consequences of impaired gluconeogenesis due to ethanol metabolism?

Hypoglycemia (especially if fasting) and lactic acidosis.

In a fed state (blood glucose ~5–7 mM), which substrate is preferred for ATP production in exercising muscle, carbohydrates or fats?

Carbohydrates are preferred for ATP production in exercising muscle in a fed state.

What can be said about the role of GLUT4 in exercising muscle in a fed state?

In a fed state, insulin levels are high, stimulating GLUT4 translocation to the cell surface, leading to increased glucose uptake by muscle cells for energy.