Podcast
Questions and Answers
What role does biotin play in the conversion of pyruvate to oxaloacetate?
What role does biotin play in the conversion of pyruvate to oxaloacetate?
- It acts as a substrate for phosphoenolpyruvate.
- It facilitates the decarboxylation of oxaloacetate.
- It inhibits the activity of pyruvate carboxylase.
- It functions as a cofactor in pyruvate carboxylation. (correct)
Which of the following statements is true regarding fructose 1,6-bisphosphate in gluconeogenesis?
Which of the following statements is true regarding fructose 1,6-bisphosphate in gluconeogenesis?
- Fructose 1,6-bisphosphatase catalyzes its dephosphorylation. (correct)
- Its hydrolysis is catalyzed by glucokinase.
- It promotes the glycolytic pathway when AMP levels are high.
- It is synthesized from glucose 6-phosphate.
Which hormone primarily influences the regulation of gluconeogenesis by decreasing fructose 2,6-bisphosphate levels?
Which hormone primarily influences the regulation of gluconeogenesis by decreasing fructose 2,6-bisphosphate levels?
- Glucagon (correct)
- Epinephrine
- Cortisol
- Insulin
What is the main function of PEP-carboxykinase in gluconeogenesis?
What is the main function of PEP-carboxykinase in gluconeogenesis?
Which organ is primarily involved in converting glucose 6-phosphate to free glucose?
Which organ is primarily involved in converting glucose 6-phosphate to free glucose?
What is the primary function of gluconeogenesis?
What is the primary function of gluconeogenesis?
Which organ primarily synthesizes glucose during gluconeogenesis?
Which organ primarily synthesizes glucose during gluconeogenesis?
Under what condition does gluconeogenesis primarily take place?
Under what condition does gluconeogenesis primarily take place?
What is a direct precursor of phosphoenolpyruvate (PEP) in gluconeogenesis?
What is a direct precursor of phosphoenolpyruvate (PEP) in gluconeogenesis?
Which of the following substrates is NOT used in gluconeogenesis?
Which of the following substrates is NOT used in gluconeogenesis?
Which tissue has the greatest need for a continuous supply of glucose?
Which tissue has the greatest need for a continuous supply of glucose?
Lactate is primarily derived from which metabolic process?
Lactate is primarily derived from which metabolic process?
Why might red blood cells primarily rely on anaerobic glycolysis?
Why might red blood cells primarily rely on anaerobic glycolysis?
Flashcards
Bypass Irreversible Steps
Bypass Irreversible Steps
Gluconeogenesis avoids the irreversible steps of glycolysis to synthesize glucose from non-carbohydrate sources. These steps include the pyruvate kinase, phosphofructokinase-1 (PFK-1), and hexokinase/glucokinase reactions.
Pyruvate to PEP Conversion
Pyruvate to PEP Conversion
Gluconeogenesis converts pyruvate to phosphoenolpyruvate (PEP) by a two-step process:
- Pyruvate carboxylase converts pyruvate to oxaloacetate (OAA), requiring biotin and functioning as an anaplerotic reaction.
- PEP carboxykinase decarboxylates and phosphorylates OAA to PEP in the cytosol.
Fructose 1,6-bisphosphate Dephosphorylation
Fructose 1,6-bisphosphate Dephosphorylation
Gluconeogenesis bypasses the irreversible PFK-1 reaction of glycolysis by hydrolyzing fructose 1,6-bisphosphate to fructose 6-phosphate using fructose 1,6-bisphosphatase. This step is a crucial regulatory point.
Glucose 6-phosphate Dephosphorylation
Glucose 6-phosphate Dephosphorylation
Gluconeogenesis bypasses the irreversible hexokinase/glucokinase step by dephosphorylating glucose 6-phosphate to free glucose using glucose 6-phosphatase. This occurs primarily in the liver and kidneys.
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Regulation of Gluconeogenesis
Regulation of Gluconeogenesis
Gluconeogenesis is regulated by factors such as glucagon, substrate availability, and allosteric effectors. Glucagon increases the rate of gluconeogenesis by modulating enzyme activity and synthesis. Acetyl CoA allosterically activates pyruvate carboxylase, while AMP inhibits it.
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Gluconeogenesis
Gluconeogenesis
The process of creating glucose from non-carbohydrate sources, such as glycerol, lactate, and amino acids.
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Function of Gluconeogenesis
Function of Gluconeogenesis
To maintain blood glucose levels when dietary intake or stored glycogen is insufficient to meet the needs of the body, especially for tissues like the brain and red blood cells.
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Why is Glucose Essential?
Why is Glucose Essential?
Glucose is the primary energy source for certain tissues, like the brain and red blood cells. It's also needed for building structures like DNA and RNA.
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Substrates for Gluconeogenesis
Substrates for Gluconeogenesis
The ingredients that gluconeogenesis uses to make glucose include glycerol from fat, lactate from muscle and red blood cells, and amino acids from protein.
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Glycerol in Gluconeogenesis
Glycerol in Gluconeogenesis
Glycerol, derived from fat storage (triacylglycerol), is converted into dihydroxyacetone phosphate, a key intermediate in both glycolysis and gluconeogenesis.
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Lactate in Gluconeogenesis
Lactate in Gluconeogenesis
Lactate, produced during anaerobic glycolysis, especially in muscles and red blood cells, is transported to the liver and converted back to glucose in the Cori cycle.
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Amino Acids in Gluconeogenesis
Amino Acids in Gluconeogenesis
Amino acids, from protein breakdown, are a major source of glucose during fasting. They generate α-keto acids, which can be converted to glucose.
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Why Doesn't Gluconeogenesis Simply Reverse Glycolysis?
Why Doesn't Gluconeogenesis Simply Reverse Glycolysis?
Gluconeogenesis and glycolysis are not simply reverse processes. They have different regulatory mechanisms and key steps that are unique to each pathway.
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Gluconeogenesis Overview
- Gluconeogenesis is the process of producing glucose from non-carbohydrate precursors.
- This process is essential when dietary glucose is insufficient.
- Specific tissues, such as the brain, red blood cells, and exercising muscles, require a constant supply of glucose.
Function of Gluconeogenesis
- Gluconeogenesis produces glucose when dietary or circulating glucose levels are insufficient for tissue needs
- This happens during starvation, prolonged fasting, or abnormal glucose homeostasis.
Sources of Glucose
- Food
- Stored glycogen
- Non-carbohydrate sources (e.g., glycerol, lactate, amino acids)
Need for Glucose
- Energy: While not the only source, glucose is the preferred source for some tissues (e.g., brain)
- Synthesis of ribose for nucleotide production: (e.g., DNA/RNA)
- Synthesis of glycoproteins and glycolipids.
When Gluconeogenesis Occurs
- When blood glucose levels drop too low to maintain cell/tissue demands.
Substrates for Gluconeogenesis
- Glycerol: Derived from triglycerides. The liver phosphorylates glycerol to glycerol-3-phosphate. It's then oxidized to dihydroxyacetone phosphate, an intermediate in glycolysis. This traps the glycerol molecule within the cell.
- Lactate: Derived from anaerobic glycolysis (e.g., exercising muscle). Lactate is transported to the liver and eventually converted back to glucose—part of the Cori cycle.
- Amino acids: Especially alanine, derived from protein breakdown. Catabolism produces α-keto acids like α-ketoglutarate, creating oxaloacetate—a crucial precursor to phosphoenolpyruvate.
Glycolysis vs. Gluconeogenesis
- Glycolysis and gluconeogenesis are not simply reverse processes.
- Gluconeogenesis uses unique steps to bypass the three irreversible steps of glycolysis.
Pyruvate to Phosphoenolpyruvate
- Pyruvate carboxylase converts pyruvate to oxaloacetate.
- Oxaloacetate is decarboxylated and phosphorylated by PEP carboxykinase to form phosphoenolpyruvate..
Conversion of PEP to Fructose 1,6-Bisphosphate
- The reactions involved reverse the direction of glycolysis.
Dephosphorylation of Fructose 1,6-Bisphosphate
- Fructose 1,6-bisphosphatase hydrolyzes fructose 1,6-bisphosphate bypassing the PFK-1 step in glycolysis.
- This step is hormonally regulated (e.g., high AMP, low insulin/high glucagon ratios).
Dephosphorylation of Glucose 6-Phosphate
- Glucose 6-phosphatase removes the phosphate group from glucose 6-phosphate, producing free glucose.
- The liver and kidneys are the only organs capable of this process
Regulation of Gluconeogenesis
- Glucagon plays a crucial role, influencing allosteric effectors and enzyme activity (e.g., phosphorylation of key enzymes).
- Substrate availability (e.g., amino acids, glycerol) also impacts the rate of gluconeogenesis.
- Hormonal regulation (e.g., insulin/glucagon ratio) has a significant effect.
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