Ketone bodies
)[2] Ketone bodies are also produced in glial cells under periods of food restriction to sustain memory formation.
In all other tissues, the fatty acids that enter the metabolizing cells are combined with coenzyme A to form acyl-CoA chains.
[2][8] The acetyl-CoA produced by β-oxidation enters the citric acid cycle in the mitochondrion by combining with oxaloacetate to form citrate.
In the liver oxaloacetate is wholly or partially diverted into the gluconeogenic pathway during fasting, starvation, a low carbohydrate diet, prolonged strenuous exercise, and in uncontrolled type 1 diabetes mellitus.
[2] In the liver, therefore, oxaloacetate is unavailable for condensation with acetyl-CoA when significant gluconeogenesis has been stimulated by low (or absent) insulin and high glucagon concentrations in the blood.
All cells with mitochondria can take ketone bodies up from the blood and reconvert them into acetyl-CoA, which can then be used as fuel in their citric acid cycles, as no other tissue can divert its oxaloacetate into the gluconeogenic pathway in the way that the liver does this.
[2] The occurrence of high levels of ketone bodies in the blood during starvation, a low carbohydrate diet and prolonged heavy exercise can lead to ketosis, and in its extreme form in out-of-control type 1 diabetes mellitus, as ketoacidosis.
On the other hand, most people can smell acetone, whose "sweet & fruity" odor also characterizes the breath of persons in ketosis or, especially, ketoacidosis.
Ketone bodies are transported from the liver to other tissues, where acetoacetate and β-hydroxybutyrate can be reconverted to acetyl-CoA to produce reducing equivalents (NADH and FADH2), via the citric acid cycle.
Acetone in high concentrations, as can occur with prolonged fasting or a ketogenic diet, is absorbed by cells outside the liver and metabolized through a different pathway via propylene glycol.
Though the pathway follows a different series of steps requiring ATP, propylene glycol can eventually be turned into pyruvate.
[12] For several decades the liver has been considered as the main supplier of ketone bodies to fuel brain energy metabolism.
However, recent evidence has demonstrated that glial cells can fuel neurons with locally synthesized ketone bodies to sustain memory formation upon food restriction.
[15] Many studies suggest that human brain cells can survive with little or no glucose, but proving the point is ethically questionable.
Under these circumstances, the low or absent insulin levels in the blood, combined with the inappropriately high glucagon concentrations,[19] induce the liver to produce glucose at an inappropriately increased rate, causing acetyl-CoA resulting from the beta-oxidation of fatty acids, to be converted into ketone bodies.
