Brain starvation

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 ... 

The first hormonal signal found to comply with the characteristics of both a satiety and an adiposity signal was insulin [1]. Insulin levels reflect substrate (carbohydrate) intake and stores, as they rise with blood glucose levels and fall with starvation. In addition, they may reflect the size of adipose stores, because a fatter person secretes more insulin than a lean individual in response to a given increase of blood glucose. This increased insulin secretion in obesity can be explained by the reduced insulin sensitivity of liver, muscle, and adipose tissue. Insulin is known to enter the brain, and direct administration of insulin to the brain reduces food intake. The adipostatic role of insulin is supported by the observation that mutant mice lacking the neuronal insulin receptor (NDRKO mice) develop obesity. 

Starvation or disease can lead to rapid release of the stored xenobiotic and to delayed toxic effects. In one well-documented case in the Netherlands (see Chapter 5), wild female eider ducks (Somateria mollissima) experienced delayed neurotoxicity caused by dieldrin. The ducks had laid down large reserves of depot fat before breeding, and these reserves were run down during the course of egg laying. Dieldrin concentrations quickly rose to lethal levels in the brain. Male eider ducks did not lay down and mobilize body fat in this way and did not show delayed neurotoxicity due to dieldrin. 

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. 

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

Figure 1-16-5. Fuel Use in the Brain During Fasting and Starvation...

In the options above, each graph depicts the primary source of fuel used by the brain during fasting/starvation. For each condition listed below, select the most closely matched graph. 

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.

The extract from Colin Blakemore s book provides a vivid account of the behavionral consequences of a low blood glucose level. This is because the brain uses glucose as the only fuel, except in prolonged starvation. Problems also arise if the blood glucose level increases well above the normal. An increase of only about twofold above the... 

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). 

Ketone bodies are oxidised by most aerobic tissues including skeletal muscle, heart, kidney, lung, intestine and brain. Since the last two cannot oxidise fatty acids, their ability to oxidise ketone bodies is very important, because they provide another fuel in addition to, or as an alternative to, glucose. Hence, they can be used to replace some of the glucose to maintain the blood glucose concentration (e.g. in prolonged starvation or hypoglycaemia). 

Figure 7.21 Provision of the fat fueb for the brain during hypo-glycaemia. During hypoglycaemia it is essential that ketone bodies are available for the brain to provide a fat fuel for ATP generation to maintain mental functions. This sequence of processes from adipose tissue to the brain is therefore, a survival pathway especially for children during short-term starvation or hypoglycaemia. (Box 7.2) (Chapter 16).

In the 1970s the physiological importance of ketone bodies was revived, quite dramatically, when George Cahill and his colleagues demonstrated that ketone bodies could be used by the human brain during prolonged starvation and, furthermore, contributed significantly to ATP... 

The situation is, however, different in starvation. In this condition, it is the degradation of muscle protein that provides the amino acids for gluconeo-genesis, so that all the oxo-acids generated (except those for lysine and lencine) are nsed to synthesise the glucose required for oxidation by the brain. Hence, a process other than amino acid oxidation mnst generate the ATP required by gluconeogenesis. This process is fatty acid oxidation. 

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