Ketone Bodies

• Ketone bodies are acetone, acetoacetate, and D-beta-hydroxybutyrate. They are formed from acetyl-CoA in the liver.
• Aceton is exhaled.
• Acetoacetate and D-beta-hydroxybutyrate are transported to extrahepatic tissues and converted to acetyl-CoA to be oxidized in the citric acid cycle.
• Acetone resulting from ketone body production is:

  • Removed from the body by exhalation
  • Used as fuel in tissues other than the liver
  • Not a ketone body
  • Produced by nonenzymatically and enzymatically by decarboxylation of D-beta-hydroxybutyrate


  Removed from the body by exhalation
• Acetone, a volatile compound produced in smaller quantities than other ketone bodies, is exhaled. The exhaled acetone imparts a characteristic odor to the breath.
• Ketone bodies, formed in the liver, are exported to other organs as fuel.
• Thiolase catalyzes the enzymatic condensation of two acetyl-CoA molecules to form acetoacetyl-CoA. This is a reversal of the last step of beta oxidation
• HMG-CoA synthase catalyzes the condensation of acetoacetyl-CoA with acetyl-CoA to form beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA)
• HMG-CoA lyase catalyzes the cleavage of HMG-CoA to free acetoacetate and acetyl-CoA
• Acetoacetate decarboxylase catalyzes the decarboxylation of acetoacetate to aceton
• D-beta-hydroxybutyrate dehydrogenase catalyzes the reversible reduction of acetoacetate to D-beta-hydroxybutyrate
• D-beta-hydroxybutyrate dehydrogenase catalyzes the oxidation of D-beta-hydroxybutyrate to acetoacetate in extrahepatic tissue.
• Beta-ketoacyl-CoA transferase catalyzes the activation of acetoacetate
• Acetyl-CoA enters the citric acid cycle.
• Which statement is true regarding the reactions of ketone body metabolism?

  • The enzymes that catalyze biosynthesis of ketone bodies are found in the cytosol of hepatocytes.
  • NADH is produced by catabolism of D-beta-hydroxybutyrate
  • Conversion of 2 acetyl-CoA to acetoacetyl-CoA is accompanied by hydrolysis of ATP to AMP and PPi
  • The liver lacks thiolase and therefore cannot use ketone bodies as fuel

  NADH is produced by catabolism of D-beta-hydroxybutyrate
• The oxidation of D-beta-hydroxybutyrate to acetoacetate by D-beta-hydroxybutyrate dehydrogenase reduced NAD+ to NADH
• Ketone bodies are used as fuel in all tissues except the liver
• The liver lacks beta-ketoacyl-CoA transferase
• The liver is a producer of ketone bodies, not a consumer.
• Ketone bodies are overproduced in diabetes and during starvation
• The accumulation of acetyl-CoA accelerates formation of ketone bodies .

  • extrahepatic tissues do not have the capacity to oxidize them all.
• Which molecule is produced in high concentration as a result of both enhanced gluconeogenesis during starvation and in untreated diabetes, which has the same fate under those two conditions?

  • Acetyl-CoA
  • Glyceraldehyde 3-phosphate
  • Succinate
  • NADH
  • FADH2

  Aceyl-CoA
• The citric acid cycle is severely slowed under both conditions, and acetyl-CoA concentrations increase, leading to acetoacetate formation, ie ketone bodies.
• Acidosis is lowered blood pH that can be caused by increased levels of acetoacetate, and D-beta-hydroxybutyrate
• Ketosis is when there are high levels of ketone bodies in the blood and urine
• Ketoacidosis is the condition when ketosis and acidosis are combined.
• Acetoacetate decarboxylase catalyzes the decarboxylation of acetoacetate to acetone
• Individuals with untreated diabetes produce large quantities of acetoacetate
• Acetone formed from the decarboxylation of acetoacetate is volatile. It imparts a characteristic odor to the breath.
• Starvation and uncontrolled diabetes mellitus can both result in

  • Ketosis, implying the body of a person with uncontrolled diabetes mellitus is acting metabolically as though starving
  • Ketosis, implying that ketoacidosis is a result of uncontrolled diabetes mellitus but not starvation
  • Ketosis, implying that high levels of ketone bodies in the blood must be well tolerated
  • Ketosis, where cells are impaired in the uptake of ketone bodies


  Ketosis, implying that the body of a person with uncontrolled diabetes mellitus is acting metabolically as though it is starving.
• When the insulin level is insufficient, extrahepatic tissues cannot take up glucose efficiently from the blood. Fatty acid oxidation increases, but the resulting acetyl-CoA cannot pass through the citric acid cycle because cycle intermediates have been drawn off for use as substrates in gluconeogenesis. The accumulation of acetyl-CoA accelerates the formation of ketone bodies.