Ketone bodies brain

The primary fate of acetyl CoA under normal metabolic conditions is degradation in the citric acid cycle to yield C02. When the body is stressed by prolonged starvation, however, acetyl CoA is converted into compounds called ketone bodies, which can be used by the brain as a temporary fuel. Fill in the missing information indicated by the four question marks in the following biochemical pathway for the synthesis of ketone bodies from acetyl CoA ... 

Brain Coordination of the nervous system Glycolysis, amino acid metabolism Glucose, amino acid, ketone bodies (in starvation) Polyunsaturated fatty acids in neonate Lactate ... 

In starvation, glucose must be ptovided for the brain and erythrocytes initially, this is supphed from hver glycogen reserves. To spare glucose, muscle and other tissues reduce glucose uptake in response to lowered insuhn secretion they also oxidize fatty acids and ketone bodies preferentially to glucose. 

Brain Brain does not burn fat as an energy source however, after adapting to long-term starvation, brain can use ketone bodies for fuel. 

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). 

Brain, which is usually very reliant on glucose for energy, adapts in a few days of starvation to use ketone bodies as a source of energy. This spares the body some glucose, which is still essential to maintain red cell function. 

The formation of ketone bodies is a consequence of prolonged metabolism of fat (Fig. 17-12). Their formation in the liver actually enables liver to metabolize even more fat by freeing up CoA that would otherwise be tied up as acetyl-CoA waiting to get into the TCA cycle. The liver exports the ketone bodies and other tissues, particularly the brain, can adapt to use them. 

With increasing metabolism of fat through p oxidation, much of the mitochondrial CoA pool may become tied up as acyl- or acetyl-CoA. In such cases, the supply of free CoA can be diminished, and this may limit the rate of p oxidation. Upon prolonged fasting and heavy reliance on fat for energy, the liver induces the enzymes required for the formation of ketone bodies and brain induces enzymes required for their metabolism. 

KETONE BODIES are generated by the liver and used by muscle and brain (after adaptation during starvation). 

Nehhg, A. Brain uptake and metabolism of ketone bodies in animal models. Prostaglandins Leukot. Essent. Fatty Acids 70 265-275, 2004. 

Patel, M. S., Johnson, C. A., Rajan, R. etal. The metabolism of ketone bodies in developing human brain development of ketone-body-utilizing enzymes and ketone bodies as precursors for lipid synthesis. /. Neurochem. 25 905-908, 1975. 

The role of fatty acids as oxidizable fuels for brain metabolism is negligible, but ketone bodies, derived from fatty acid oxidation, can be utilized, particularly in the neonatal period. Diseases of carbohydrate and fatty acid metabolism may affect the brain directly or indirectly [1,10]. 

Finally, we may add that fluorocitrate interferes with fat metabolism in vivo, because it leads to rapid and marked urinary appearance of ketone bodies.1 Unlike fluoroacetate, intraperi-toneal fluorocitrate (20 mg./kg.) (synthetic), though increasing the citrate in the brain, produces no convulsions in 2 hr. 

Because glucose is the preferred fuel for the brain, an individual who experiences a rapid fall in glucose concentration leading to acute neuroglycopenia will initially feel confusion and may progress to coma and even death. In the event that the person survives 3-4 days, the brain can adapt its metabolism to utilize ketone bodies, metabolically derived from acetyl-CoA (see Figure 6.17), as a source of energy. 

Although the acetyl CoA from fatty acids cannot he converted to glucose, it can be converted to ketone bodies as an alternative fuel for cells, induding the brain. Chronic hypoglycemia is thus often accompanied physiologically by an increase in ketone bodies. 

In the brain, when ketones are metabolized to acetyl CoA, pyruvate dehydrogenase is inhibited. Glycolysis and subsequently glucose uptake in brain decreases. This important switch spares body protein (which otherwise would be catabolized to form glucose by gluconeogenesis in the liver) by allowing the brain to indirectly metabolize fetty acids as ketone bodies. 

Figure 3.18 Oxidation of glucose and ketone bodies by the brain. Glucose is the sole fuel used by the brain, except in prolonged starvation in adults or relatively short-term starvation in children. In both cases, ketone bodies plus glucose are used.

Ketone bodies (acetoacetate, hydroxybutyrate) free liver cardiac muscle, brain, kidney, skeletal muscle, small intestine... 

During starvation or hypoglycaemia, the liver partially oxidises fatty acids to form ketone bodies, which are released and oxidised by the brain, intestine and the essential muscles (see below) (Figure 7.7). 

Acetoacetate and 3-hydroxybutyrate are known as ketone bodies. They are classified as fat fuels since they arise from the partial oxidation of fatty acids in the liver, from where they are released into the circulation and can be used by most if not all aerobic tissues (e.g. muscle, brain, kidney, mammary gland, small intestine) (Figure 7.7, Table 7.1). There are two important points (i) ketone bodies are used as fuel by the brain and small intestine, neither of which can use fatty acids (ii) ketone bodies are soluble in plasma so that they do not require albumin for transport in the blood. 

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