Podcast
Questions and Answers
Why can't the liver utilize ketone bodies as fuel?
Why can't the liver utilize ketone bodies as fuel?
The liver lacks β-ketoacyl-CoA transferase, preventing it from using ketone bodies as fuel.
What are the conditions under which ketone body production increases significantly?
What are the conditions under which ketone body production increases significantly?
Ketone body production increases during starvation and untreated diabetes mellitus.
How does starvation affect the citric acid cycle and ketone body production?
How does starvation affect the citric acid cycle and ketone body production?
Starvation depletes citric acid cycle intermediates, diverting acetyl-CoA towards ketone body production.
What hormonal condition affects glucose uptake in extrahepatic tissues during untreated diabetes?
What hormonal condition affects glucose uptake in extrahepatic tissues during untreated diabetes?
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What health risks can arise from elevated levels of ketone bodies in the blood?
What health risks can arise from elevated levels of ketone bodies in the blood?
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What are the primary ketone bodies produced in the liver?
What are the primary ketone bodies produced in the liver?
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How does the brain adapt to use ketone bodies under starvation conditions?
How does the brain adapt to use ketone bodies under starvation conditions?
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What is the first step in the formation of acetoacetate from acetyl-CoA?
What is the first step in the formation of acetoacetate from acetyl-CoA?
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What role does the enzyme d-β-hydroxybutyrate dehydrogenase play in ketone body metabolism?
What role does the enzyme d-β-hydroxybutyrate dehydrogenase play in ketone body metabolism?
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What happens to acetoacetate in the extrahepatic tissues?
What happens to acetoacetate in the extrahepatic tissues?
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Why can't the brain use fatty acids as a fuel source?
Why can't the brain use fatty acids as a fuel source?
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What is the function of β-ketoacyl-CoA transferase in ketone body metabolism?
What is the function of β-ketoacyl-CoA transferase in ketone body metabolism?
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How is the production and export of ketone bodies beneficial for the liver?
How is the production and export of ketone bodies beneficial for the liver?
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Study Notes
Ketone Bodies and Their Metabolism
- Acetyl-CoA from fatty acid oxidation in the liver can enter the citric acid cycle or be converted into ketone bodies: acetone, acetoacetate, and d-β-hydroxybutyrate.
- Acetone is primarily exhaled, while acetoacetate and d-β-hydroxybutyrate are transported via blood to tissues for energy.
- Skeletal muscle, heart muscle, and renal cortex utilize ketone bodies as a significant energy source.
- The brain typically relies on glucose but can adapt to using acetoacetate and d-β-hydroxybutyrate when glucose is scarce during starvation.
- Fatty acids cannot be used as fuel by the brain due to the blood-brain barrier.
Production and Conversion of Ketone Bodies
- Ketone body production begins in the liver with the enzymatic condensation of two acetyl-CoA molecules, catalyzed by thiolase.
- The product, acetoacetyl-CoA, further condenses with another acetyl-CoA to form β-hydroxy-β-methylglutaryl-CoA (HMG-CoA), which is cleaved into acetoacetate and acetyl-CoA.
- Acetoacetate can be reversibly reduced to d-β-hydroxybutyrate by d-β-hydroxybutyrate dehydrogenase, which is stereospecific for the d form.
- This stereospecificity allows the cell to maintain separate pools of β-hydroxyacyl-CoAs for either breakdown (fatty acid oxidation) or synthesis (fatty acid synthesis).
Utilization of Ketone Bodies
- In extrahepatic tissues, d-β-hydroxybutyrate is oxidized back to acetoacetate by d-β-hydroxybutyrate dehydrogenase.
- Acetoacetate is activated by transferring CoA from succinyl-CoA in a reaction catalyzed by β-ketoacyl-CoA transferase (thiophorase).
- Acetoacetyl-CoA is then cleaved by thiolase to generate two acetyl-CoA molecules, which enter the citric acid cycle.
- Liver does not consume ketone bodies since it lacks β-ketoacyl-CoA transferase, functioning mainly as a producer for other tissues.
Implications of Starvation and Diabetes
- Starvation, very-low-calorie diets, and untreated diabetes mellitus can cause excessive production of ketone bodies.
- During starvation, gluconeogenesis depletes intermediates from the citric acid cycle, leading to increased ketone body production.
- In untreated diabetes, insufficient insulin prevents extrahepatic tissues from effectively utilizing glucose, leading to the production of fatty acids and escalated ketone body levels.
- Rising levels of acetoacetate and d-β-hydroxybutyrate in blood can result in acidosis, marked by lowered blood pH.
- Extreme acidosis can be fatal, with potentially elevated ketone body concentrations in blood and urine, reaching levels significantly above normal.
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Description
This quiz explores the liver's inability to utilize ketone bodies as fuel, the conditions that lead to increased ketone production, and how starvation impacts the citric acid cycle. Additionally, it examines hormonal influences on glucose uptake during untreated diabetes and the health risks associated with high levels of ketone bodies in the blood.