Podcast
Questions and Answers
Which of the following conditions is associated with gluconeogenesis?
Which of the following conditions is associated with gluconeogenesis?
- Cori's Disease
- Von Gierke’s Disease (correct)
- Phenylketonuria
- Maple Syrup Urine Disease
What is one of the functions of gluconeogenesis?
What is one of the functions of gluconeogenesis?
- Maintains adequate blood sugar during starvation (correct)
- Generates glucose from fatty acid
- Synthesis of steroids
- Supports anaerobic respiration
Which tissues require a continuous supply of glucose?
Which tissues require a continuous supply of glucose?
- Brain and lens of the eye (correct)
- Cartilage and Bone
- Adipose tissues
- Skeletal muscle
Gluconeogenesis allows the use of which substrate during extended exercise?
Gluconeogenesis allows the use of which substrate during extended exercise?
What role does gluconeogenesis play in metabolic acidosis?
What role does gluconeogenesis play in metabolic acidosis?
Which process contributes to glucose generation from intermediates of the TCA cycle?
Which process contributes to glucose generation from intermediates of the TCA cycle?
Which deficiency is closely related to the impact on gluconeogenesis?
Which deficiency is closely related to the impact on gluconeogenesis?
During periods of low carbohydrate intake, which metabolic pathway becomes more active?
During periods of low carbohydrate intake, which metabolic pathway becomes more active?
Which of the following does NOT require a continuous glucose supply?
Which of the following does NOT require a continuous glucose supply?
What is the primary source for gluconeogenesis?
What is the primary source for gluconeogenesis?
What is the primary location for gluconeogenesis under normal conditions?
What is the primary location for gluconeogenesis under normal conditions?
Which of the following compounds can serve as gluconeogenic precursors?
Which of the following compounds can serve as gluconeogenic precursors?
During starvation, which organ may contribute up to 50% of the glucose produced through gluconeogenesis?
During starvation, which organ may contribute up to 50% of the glucose produced through gluconeogenesis?
What is the first step in the gluconeogenic pathway?
What is the first step in the gluconeogenic pathway?
Which enzyme is involved in the conversion of Fructose 1,6-Bisphosphate to Fructose 6-Phosphate?
Which enzyme is involved in the conversion of Fructose 1,6-Bisphosphate to Fructose 6-Phosphate?
What is a major substrate for gluconeogenesis derived from triglycerides?
What is a major substrate for gluconeogenesis derived from triglycerides?
Which metabolic condition would most likely increase gluconeogenesis in the kidneys?
Which metabolic condition would most likely increase gluconeogenesis in the kidneys?
What is one of the final steps in the gluconeogenic pathway after the conversion of G6P?
What is one of the final steps in the gluconeogenic pathway after the conversion of G6P?
What are ketogenic compounds primarily used for in metabolism?
What are ketogenic compounds primarily used for in metabolism?
Which of the following mechanisms does glucagon NOT utilize to stimulate gluconeogenesis?
Which of the following mechanisms does glucagon NOT utilize to stimulate gluconeogenesis?
What effect does glucagon have on fructose 2,6-bisphosphate levels?
What effect does glucagon have on fructose 2,6-bisphosphate levels?
How does glucagon induce covalent modification of enzyme activity?
How does glucagon induce covalent modification of enzyme activity?
What role does fructose 2,6-biphosphate play in glucose metabolism?
What role does fructose 2,6-biphosphate play in glucose metabolism?
Which statement is true regarding insulin's role in gluconeogenesis?
Which statement is true regarding insulin's role in gluconeogenesis?
Where does glucose 6-phosphate dephosphorylation primarily occur?
Where does glucose 6-phosphate dephosphorylation primarily occur?
Which hormones stimulate the synthesis of enzymes needed for gluconeogenesis?
Which hormones stimulate the synthesis of enzymes needed for gluconeogenesis?
Why can't glucose 6-phosphate derived from muscle glycogen yield free glucose?
Why can't glucose 6-phosphate derived from muscle glycogen yield free glucose?
What is the role of fructose 1,6-bisphosphatase in gluconeogenesis?
What is the role of fructose 1,6-bisphosphatase in gluconeogenesis?
What is the effect of glucagon on fructose 2,6-biphosphate levels?
What is the effect of glucagon on fructose 2,6-biphosphate levels?
Which enzyme's activity is inhibited by increased fructose 2,6-bisphosphate levels?
Which enzyme's activity is inhibited by increased fructose 2,6-bisphosphate levels?
Which enzyme is responsible for the irreversible step in gluconeogenesis that fructose 2,6-biphosphate inhibits?
Which enzyme is responsible for the irreversible step in gluconeogenesis that fructose 2,6-biphosphate inhibits?
What is the primary impact of glucagon on pyruvate kinase activity?
What is the primary impact of glucagon on pyruvate kinase activity?
How does fructose 2,6-biphosphate serve as an example of reciprocal control?
How does fructose 2,6-biphosphate serve as an example of reciprocal control?
What is one of the key functions of glucagon in relation to glycolysis?
What is one of the key functions of glucagon in relation to glycolysis?
Which metabolic pathway does fructose 2,6-biphosphate inhibit?
Which metabolic pathway does fructose 2,6-biphosphate inhibit?
Which of the following statements about covalent modification in gluconeogenesis is correct?
Which of the following statements about covalent modification in gluconeogenesis is correct?
What is the consequence of fructose 2,6-biphosphate concentration decreasing?
What is the consequence of fructose 2,6-biphosphate concentration decreasing?
What metabolic effect does the presence of fructose 2,6-biphosphate have on glucose 6-phosphatase?
What metabolic effect does the presence of fructose 2,6-biphosphate have on glucose 6-phosphatase?
Which factor has a prominent influence on the rate of hepatic glucose synthesis?
Which factor has a prominent influence on the rate of hepatic glucose synthesis?
What is the result of decreased insulin levels in the context of gluconeogenesis?
What is the result of decreased insulin levels in the context of gluconeogenesis?
What causes the accumulation of acetyl CoA during starvation?
What causes the accumulation of acetyl CoA during starvation?
Which enzyme is inhibited by elevated AMP levels?
Which enzyme is inhibited by elevated AMP levels?
What effect does acetyl CoA have in gluconeogenesis when it accumulates in the liver?
What effect does acetyl CoA have in gluconeogenesis when it accumulates in the liver?
What is the effect of AMP elevation on metabolic pathways?
What is the effect of AMP elevation on metabolic pathways?
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Study Notes
Overview of Gluconeogenesis
- Gluconeogenesis is the synthesis of carbohydrates from noncarbohydrate precursors.
- Primarily occurs in the liver (85-95% of glucose production); kidneys contribute 10%, especially during starvation or metabolic acidosis.
Substrates for Gluconeogenesis
- Key gluconeogenic precursors include lactate, pyruvate, alanine, glycerol (from triglycerides), alpha-keto acids, and specific amino acids.
Pathway Steps
- Begins with pyruvate carboxylation.
- Oxaloacetate (OAA) is transported to the cytosol.
- Cytosolic OAA undergoes decarboxylation.
- Conversion of phosphoenolpyruvate (PEP) to fructose 1,6-bisphosphate (F1,6-BP) occurs.
- Fructose 1,6-BP is dephosphorylated to fructose 6-phosphate (F6P).
- Glucose 6-phosphate (G6P) is dephosphorylated to yield free glucose.
Regulation of Gluconeogenesis
- Hormonal regulation involves glucagon, insulin, and epinephrine which influence enzyme activity.
- Non-hormonal regulation is dependent on substrate availability and allosteric effectors.
Hormonal Regulation
- Glucagon stimulates gluconeogenesis via:
- Lowering fructose 2,6-bisphosphate levels, activating fructose 1,6-bisphosphatase and inhibiting phosphofructokinase (PFK).
- Covalent modification of enzymes, converting pyruvate kinase to an inactive form.
- Inducing enzyme synthesis for gluconeogenesis enzymes while suppressing glycolytic enzymes (hexokinase, PFK, and pyruvate kinase).
- Insulin suppresses gluconeogenesis while promoting glycolysis.
Non-Hormonal Regulation
- Substrate availability is crucial; decreased insulin levels lead to amino acid mobilization for carbon skeletons in gluconeogenesis.
- Allosteric activation occurs when there is an accumulation of acetyl CoA from fatty acid oxidation during starvation.
- AMP serves as an allosteric inhibitor of fructose 1,6-bisphosphatase, stimulating PFK and energy-producing pathways.
Functions of Gluconeogenesis
- Generates glucose from glycolysis intermediates, fatty acids, or TCA cycle products.
- Maintains blood sugar levels during starvation or low carbohydrate intake.
- Excretes protons during metabolic acidosis.
- Utilizes dietary protein in carbohydrate pathways.
- Uses lactate during prolonged exercise.
Continuous Glucose Requiring Tissues
- Essential organs and tissues include the brain, lens and cornea of the eye, red blood cells (RBCs), testes, renal medulla, and exercising muscle.
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