Ketone Bodies
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Introduction
The use of ketone bodies as fuel by most tissues during a fast reduces the need for gluconeogenesis from amino acid carbon skeletons, slowing the loss of essential protein.
During a fast, the liver is flooded with liberated FAs from adipose tissue. Liver mitochondria have the capacity to convert excess acetyl CoA, derived from fatty acid oxidation, into ketone bodies when the amount of Acetyl CoA exceeds oxidative capacity.
These include acetoacetate, 3-hydroxybutyrate, and acetone.
As ketone bodies are soluble, they can be transported in the blood to peripheral tissues where they can be reconverted into Acetyl CoA and oxidized in the TCA cycle.
Production of Ketone Bodies
During a fast, the liver is flooded with liberated FAs from adipose tissue. This inhibits pyruvate dehydrogenase in the TCA cycle and activates pyruvate carboxylase, shunting pyruvate towards OAA for transport out of the mitochondria and into gluconeogenesis. This leaves Acetyl CoA available for ketone body synthesis.
HMG CoA Synthase is the rate limiting step of ketone body synthesis.
Use of Ketone Bodies
Ketone bodies are reconverted into acetyl CoA in the periphery, including brain, heart and muscle, although the liver cannot use them as fuel.
Excessive Production of Ketone Bodies
Excessive ketone production results in ketonemia and ketonuria, often observed in Type I diabetes. This results from high levels of fatty acid degradation and concomitant acetyl CoA synthesis. In diebetic individuals, urinary excretion can be as high as 5000 mg/d, and blood levels can go from 3 mg/dl (normal) to 90 mg/dl.
Elevated ketone levels causes acidemia, as the pKa of the carboxyl group is 4. Excretion of glucose and ketone bodies also causes dehydration, and as a result, profound acidosis can occur.
Ketoacidosis can also be the result of profound fasting.
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