3 ketone bodies

• Ketone bodies


  • Acetone
  • Acetoacetate
  • β-hydroxybutyrate
• Ketogenesis


  Synthesis of ketone bodies in the liver
• Ketogenesis reactions


  1. Condensation of acetyl CoA to acetoacetyl CoA

  2. Formation of HMG CoA

  3. Cleavage of HMG CoA to acetoacetate and acetyl CoA

  4. Decarboxylation of acetoacetate to form acetone

  5. Reduction of acetoacetate to β-hydroxybutyrate
• Ketone bodies serve as important sources of energy for peripheral tissues.
• The production of ketone bodies becomes significant when glucose is in short supply.
• During prolonged starvation, ketone bodies are the major fuel source for the brain.
• The brain can utilize 50-70% of its energy needs from ketone bodies.
• In normal individuals, there is a constant production of ketone bodies by the liver.
• Ketonemia is when the rate of synthesis of ketone bodies exceeds the rate of utilization.
• Ketonuria represents the excretion of ketone bodies in urine.
• Ketosis is the overall picture of ketonemia and ketonuria.
• Smell of acetone in breath is a common feature in ketosis.
• Ketosis is most commonly associated with starvation and severe uncontrolled diabetes mellitus.
• Starvation causes increased degradation of fatty acids to meet energy needs.
• Starvation results in an accumulation of acetyl CoA and overproduction of ketone bodies.
• Diabetes mellitus is associated with insulin deficiency.
• Ketonemia


  Increase in concentration of ketone bodies in blood
• Ketonuria


  Excretion of ketone bodies in urine
• Ketosis


  Overall picture of ketonemia and ketonuria
• Common feature in ketosis

  • Smell of acetone in breath
• Ketosis is most commonly associated with

  Starvation and severe uncontrolled diabetes mellitus
• Starvation is accompanied by increased degradation of fatty acids to meet the energy needs of the body
• Starvation causes an overproduction of acetyl CoA which cannot be fully handled by the citric acid cycle
• TCA cycle is impaired due to deficiency of oxaloacetate
• Most oxaloacetate is diverted for glucose synthesis
• Accumulation of acetyl CoA leads to overproduction of ketone bodies
• Diabetes mellitus is associated with insulin deficiency
• Insulin deficiency results in impaired carbohydrate metabolism and increased lipolysis
• In severe diabetes, ketone body concentration in blood plasma may reach 100 mg/dl
• In severe diabetes, urinary excretion of ketone bodies may be as high as 500 mg/day
• Regulation of ketogenesis


  Ketone body formation occurs primarily due to non-availability of carbohydrates to the tissues
• Glucagon


  Stimulates ketogenesis
• Insulin


  Inhibits ketogenesis
• In diabetes mellitus


  Increased ratio of glucagon/insulin promotes ketone body formation
• Ketogenic substances


  Promote ketone body formation
• Antiketogenic substances


  Inhibit ketone body formation
• Ketogenic substances


  • Fatty acids
  • Certain amino acids (leucine, lysine, tyrosine)
• Antiketogenic substances


  • Glucose
  • Glycerol
  • Glucogenic amino acids (glycine, alanine, serine, glutamate)
• Both acetoacetate and β-hydroxybutyrate are strong acids
• Increase in their concentration in blood would cause acidosis