Brain glucose requirements

The ATP required by the human brain is obtained from the complete oxidation of glucose it requires about 4 g of glucose per hour. If the same amount of ATP were to be generated from the conversion of glucose to lactate, approximately 60 g per hour would be required (i.e. almost 1.5 kg of glucose each day). 

Since much less glucose is required by the brain, the rate of gluconeogenesis falls and hence the rate of protein degradation falls. In the obese, the energy provided from the oxidation of glncose that has been provided by amino acids from protein degradation is as little as 5% of the total (it is much higher in the lean see below). 

Figure 16.11 Pattern of fuel utilisation during prolonged starvation. The major metabolic change during this period is that the rates of ketone body formation and their utilisation by the brain increases, indicated by the increased thickness of lines and arrows. Since less glucose is required by the brain, gluconeogenesis from amino acids is reduced so that protein degradation in muscle is decreased. Note thin line compared to that in Figure 16.9.

The other major class of transporter protein is the carrier protein. A prototypic example of a carrier protein is the large neutral amino acid transporter. An important function of the LNAA transporter is to transport molecules across the blood-brain barrier. As discussed previously, most compounds cross the BBB by passive diffusion. However, the brain requires certain compounds that are incapable of freely diffusing across the BBB phenylalanine and glucose are two major examples of such compounds. The LNAA serves to carry phenylalanine across the BBB and into the central nervous system. Carrier proteins, such as the LNAA transporter, can be exploited in drug design. For example, highly polar molecules will not diffuse across the BBB. However, if the pharmacophore of this polar molecule is covalently bonded to another molecule which is a substrate for the LNAA, then it is possible that the pharmacophore will be delivered across the BBB by hitching a ride on the transported molecule. 

Choose the ONE correct answer 23.1 In which one of the following tissues is glucose transport into the cell enhanced by insulin A. Brain B. Lens C. Red blood cells D. Adipose tissue E. Liver Correct answer = D. The major tissues in which glucose transport requires insulin are muscle and adipose tissue. The metabolism of the liver responds to insulin, but hepatic glucose transport is rapid and does not require insulin. 

Carbohydrates are more plentiful and constant in food supplies throughout the world when compared to other nutrients, such as proteins, vitamin A, folic acid, and iodine. A naturally occurring deficiency specifically in carbohydrates is im-known. However, deliberate omission of carbohydrates from the diet with continued consumption of fat as an energy source can lead to specific problems. Glucose is required as an energy source by the central nervous system. When there is a deficiency of glucose, the body adjusts its metabolism to provide ketone bodies, nutrients derived from fat, which can be utilized by the brain and other parts of the central nervous system. However, excessive production of the ketone bodies can result in acidosis, a lowering of the pH of the blood, which is potentially toxic. 

The liver has the major responsibility for maintaining blood glucose levels. Glucose is required particularly by tissues such as the brain and red blood cells. The brain oxidizes glucose to C02 and H20, and red blood cells oxidize glucose to pyruvate and lactate. 

During fasting in humans, virtually all the glucose reserves are consumed in the first day. The brain requires glucose... 

A PET scan requires a substance called a tracer. A suitable tracer must accumulate in the target organ, and it must be modified to contain unstable radioactive atoms that emit positrons. Glucose is used for brain imaging, because the brain processes glucose as the fuel for mental and neural activities. A common tracer for PET brain scans is glucose modified to contain radioactive fluorine atoms. Our molecular inset shows a simplified model of this modified glucose molecule. 

ATP certainly fulfils the criteria for a NT. It is mostly synthesised by mitochondrial oxidative phosphorylation using glucose taken up by the nerve terminal. Much of that ATP is, of course, required to help maintain Na+/K+ ATPase activity and the resting membrane potential as well as a Ca +ATPase, protein kinases and the vesicular binding and release of various NTs. But that leaves some for release as a NT. This has been shown in many peripheral tissues and organs with sympathetic and parasympathetic innervation as well as in brain slices, synaptosomes and from in vivo studies with microdialysis and the cortical cup. There is also evidence that in sympathetically innervated tissue some extracellular ATP originates from the activated postsynaptic cell. While most of the released ATP comes from vesicles containing other NTs, some... 

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