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Ketone bodies are synthesized from Acetyl-CoA only when carbohydrates are not available. Why? Describe how gluconeogenesis,...

Ketone bodies are synthesized from Acetyl-CoA only when carbohydrates are not available. Why? Describe how gluconeogenesis, TCA, ACC, and circulating hormones play a role in directing carbon toward these molecules.

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Expert Solution

Answer:

  • Ketone bodies are Chemicals that the body makes when there is not enough insulin and glucose in the blood and it must break down fat instead of the sugar glucose for energy.
  • The ketone bodies -- acetone, acetoacetate, and beta-hydroxybutyrate -- are toxic acidic chemicals.
  • In the early stages of a fast there is a shift in liver metabolism from glucose storage to glucose production, coupled with other metabolic alterations that conserve the glucose released for the maintenance of brain and central nervous system function.
  • Following an overnight fast, most of the glucose produced by the liver is utilized by the tissues with an obligatory requirement for glucose as the major fuel.
  • At this stage, tissues such as skeletal muscle are primarily using nonesterified fatty acids (NEFA) as their major fuel supply.
  • Muscle NEFA oxidation causes a decrease in glucose uptake and subsequent glucose metabolism by muscle cells and glucose transport across the muscle cell membrane is decreased.
  • Reduction in the plasma glucose concentration as a result of a prolonged fast or food deprivation will result in the production of glucose from noncarbohydrate precursors.
  • Fatty acids are mobilized from the adipose tissue as the fast takes place and gluconeogenic and ketogenic pathways are activated in the liver.
  • The plasma glucose concentration may fall significantly with the concomitant increase in plasma fatty acids and ketone bodies to about five fold and 20-fold, respectively.
  • In ketone body synthesis, an acetyl-CoA is split off from HMG-CoA, yielding acetoacetate, a four carbon ketone body that is somewhat unstable, chemically.
  • It will decarboxylate spontaneously to some extent to yield acetone.
  • Ketone bodies are made when the blood levels of glucose fall very low.
  • Ketone bodies can be converted to acetyl-CoA, which can be used for ATP synthesis via the citric acid cycle.

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