Questions and Answers
Which organ is primarily responsible for the production of ketone bodies?
What condition can arise from the excessive accumulation of ketone bodies in untreated diabetes?
Why can't acetyl-CoA be utilized in the citric acid cycle during untreated diabetes?
What triggers the overproduction of ketone bodies in starvation?
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What happens to blood levels of acetoacetate and d-β-hydroxybutyrate during untreated diabetes?
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What are the ketone bodies produced in the liver?
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Which tissue can adapt to using ketone bodies during starvation?
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What is the first step in the formation of acetoacetate?
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Which enzyme catalyzes the conversion of d-β-hydroxybutyrate to acetoacetate in extrahepatic tissues?
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How is acetoacetate activated before entering the citric acid cycle?
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Why can't the brain use fatty acids as a fuel source?
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What is the role of thiolase in the formation of acetoacetate?
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Which ketone body is produced in smaller quantities and is exhaled?
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Study Notes
Ketone Body Metabolism
- Acetyl-CoA in the liver can enter the citric acid cycle or be converted into ketone bodies: acetone, acetoacetate, and d-β-hydroxybutyrate.
- Acetone is produced in smaller amounts and is primarily exhaled.
- Acetoacetate and d-β-hydroxybutyrate are transported via blood to extrahepatic tissues, where they convert back to acetyl-CoA for energy production.
Brain's Energy Adaptation
- The brain prefers glucose but can use acetoacetate and d-β-hydroxybutyrate during starvation when glucose is scarce.
- Fatty acids cannot cross the blood-brain barrier, making ketone bodies a crucial alternative fuel source during periods of low glucose availability.
Ketone Body Formation
- First step involves the condensation of two acetyl-CoA molecules, catalyzed by thiolase, leading to the formation of acetoacetyl-CoA.
- Acetoacetyl-CoA combines with another acetyl-CoA to create HMG-CoA, which is then split into acetoacetate and acetyl-CoA.
- d-β-hydroxybutyrate is formed by the reduction of acetoacetate, mediated by d-β-hydroxybutyrate dehydrogenase, specific to the d stereoisomer.
Enzymatic Specificity and Pools
- Differences in enzyme specificity allow the cell to maintain distinct pools of β-hydroxyacyl-CoAs for breakdown or synthesis in fatty acid metabolism.
Utilization of Ketone Bodies
- In extrahepatic tissues, d-β-hydroxybutyrate is converted back to acetoacetate, activating it for entry into metabolic pathways via β-ketoacyl-CoA transferase.
- Acetoacetyl-CoA is cleaved by thiolase to produce two molecules of acetyl-CoA for the citric acid cycle.
- The liver produces ketone bodies but does not utilize them due to the lack of β-ketoacyl-CoA transferase.
Conditions Leading to Ketosis
- Starvation and untreated diabetes cause increased ketone body production due to depletion of citric acid cycle intermediates by gluconeogenesis.
- In untreated diabetes, insufficient insulin reduces glucose uptake, decreasing malonyl-CoA levels, allowing fatty acids to be oxidized, resulting in excess acetyl-CoA.
- Accumulated acetyl-CoA converts to ketone bodies, overwhelming extrahepatic tissue oxidation capacity.
Health Implications
- Elevated levels of acetoacetate and d-β-hydroxybutyrate lead to decreased blood pH, causing acidosis.
- Severe acidosis can result in coma or death.
- Blood ketone body concentrations in untreated diabetes can reach 90 mg/100 mL, significantly higher than normal levels.
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Description
Explore the metabolic pathways involving acetyl-CoA and the formation of ketone bodies in humans and mammals. This quiz covers the production, transport, and utilization of acetone, acetoacetate, and d-β-hydroxybutyrate. Test your understanding of their roles in energy metabolism, particularly during fatty acid oxidation.
