Starvation ketone body utilization

Hawkins, R.A., Mans, A.M., and Davis, D.W. (1986) Regional ketone body utilization by rat brain in starvation and diabetes. The American Journal of Physiology. 250, E169-E178. 

Fatty acids do not serve as fuel for the brain but rather are utilized for membrane synthesis. In starvation, ketone bodies generated by the liver partly replace glucose as fuel for the brain. 

Ketone bodies provide important alternative fuels to body tissues when carbohydrate is in short supply or cannot be efficiently utilized. A particular example is the central nervous systems which cannot utilize plasma fatty acids for energy. Thus in prolonged starvation, ketone bodies become more important than glusose as a fuel source. The possibility of the utilization of ketone bodies obviates the harmful degradation of muscle protein for gluconeogenesis. In addition, acetoacetate and 3-hydroxybutyrate are thought to be important precursors for lipid synthesis in neonatal brain (Webber and Edmond, 1979). 

The increased rate of ketone body utilization in starvation is essentially not determined by a raised capacity of the enz3mies of ketone body utilization. By far the most important factor would appear to be the concentration of ketone bodies in the blood. 

Skeletal muscle can utilize ketone bodies during starvation. 

Many tissues (muscle, liver, renal cortex) prefer fat for an energy supply, at least in the resting state. The exception is red blood cells and brain. These tissues depend heavily on glycolysis for energy. Red cells cannot survive without glucose (no mitochondria), but during prolonged starvation, brain can adapt to utilize fat metabolites produced by the liver (ketone bodies). 

Protein degradation rate is lowered drastically as the organism adapts to starvation. Glucagon levels remain about the same, as do ketone body and fatty acid utilization (see Figure 21.2). 

Figure 36-5. The metabolic flow during prolonged starvation. The brain adapts to use ketone bodies as a source of energy, thus decreasing its utilization of glucose.

In normal liver, only relatively small amounts of ketone bodies are formed. Their concentration in the blood is 0.5-D.8 mg per 100 ml plasma. The acetoacetate produced by this physiological K. is degraded in the peripheral musculature. Coenzyme A from succi-nyl-CoA is transferred to the acetoacetate by aceto-acetate succinyl-CoA transferase. Direct activation of acetoacetate by coenzyme A and ATP can also occur (Fig, 2). The acetoacetyl-CoA produced in either case is thioclastically cleaved into two molecules of acetyl-CoA, consuming a CoA molecule in the process. In carbohydrate deficiency (starvation, ketone-mia in ruminants), or deficient carbohydrate utilization (diabetes mellitus), K. is greatly increased. The cause of this pathological K. is a disturbance of the equilibrium between the degradation of fatty acids to acetyl-CoA and its utilization in the tricarboxylic acid cycle. The several-fold increase in the oxidation of the fatty acids leads under these conditions to an increase in the intracellular acetyl-CoA concentration. This leads to the condensation of 2 molecules of... 

The utilization of ketone bodies by the brain is not limited to the neonatal period Smith et reported a six-fold increase of the activity of 3-hydroxybutyrate dehydrogenase in rat brain in starvation. Unlike the hyperketonaemia of starvation, the hyper-ketonaemia of suckling is accompanied by normal blood glucose concentrations and it is thus possible that in the brain the ketone bodies serve another function (i.e. myeliniza-tion) apart from serving as a fuel for respiration and the sparing of glucose. 

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