Glucose transporters blood-brain barrier

Glucose transporter Blood brain barrier lp35-31.3 ( 138140)... 

The blood-brain barrier (BBB) forms a physiological barrier between the central nervous system and the blood circulation. It consists of glial cells and a special species of endothelial cells, which form tight junctions between each other thereby inhibiting paracellular transport. In addition, the endothelial cells of the BBB express a variety of ABC-transporters to protect the brain tissue against toxic metabolites and xenobiotics. The BBB is permeable to water, glucose, sodium chloride and non-ionised lipid-soluble molecules but large molecules such as peptides as well as many polar substances do not readily permeate the battier. 

Bauer H. Glucose transporters in mammalian brain development. In Introduction to the Blood-Brain Barrier (Partridge WM, Ed.), 1st Edn. Cambridge Cambridge University Press 1998, 175-187. 

Endothelial cells of the blood-brain barrier and brain cells have specific transporters for the uptake of glucose and monocarboxylic acids 533... 

Simpson, I. A., Appel, N. M., Hokari, M. etal. Blood-brain barrier glucose transporter effects of hypo- and hyperglycemia revisited. /. Neurochem. 72 238-247,1999. 

Pelligrino, D. A., LaManna, J. C., Duckrow, R. B. etal. I. Hyperglycemia and blood-brain barrier glucose transport. J. Cereb. Blood Flow Metab. 12 887-899,1992. 

Hasselbalch, S. G., Knudsen, G. M., Capaldo, B. etal. Blood-brain barrier transport and brain metabolism of glucose during acute hyperglycemia in humans. /. Clin. Endocrinol. Metab. 86 1986-1990, 2001. 

Uremia results in increased permeability of the blood-brain barrier to sucrose and insulin K+ transport is enhanced whereas Na+ transport is impaired. There is an increase in brain osmolarity in acute renal failure due to the increase in urea concentrations. However, in contrast to acute renal failure, the increase in osmolarity in chronic renal failure results from the presence of idiogenic osmoles in addition to urea. CBF is increased in uremic patients but CMR02 and CMR are decreased. In the brains of rats with acute renal failure, ATP, phosphocreatine and glucose are increased whereas AMP, ADP and lactate are decreased, most probably as a result of decreased energy demands. 

Defective transport of glucose across the blood-brain barrier is caused by deficiency in the glucose transporter protein 703... 

De Vivo, D. C., Trifiletti, R. R., Jacobson, R. I., Ronen, G. M., Behmand, R. A. and Harik, S. I. Defective glucose transport across the blood-brain barrier as a cause of persistent hypo-glycorrhachia, seizures, and developmental delay. N. Engl. J. Med. 325 703-709,1991. 

The traditional model for the processes by which glucose is made available for the neurones is that glucose is transported across the blood-brain barrier into the extracellular fluid, from where it is taken up by neurones (and gUal cells). However, there are several problems with this model ... 

The constant transport of substances among blood, CSF, and brain cells is influenced by the blood-brain barrier (BBB) (Section 3.2.1). The transport function of the BBB depends on the concentration gradient, molecular weight, ion composition, and liposolubility of compounds as well as on the presence of specific transmitters (i.e., glucose and amino acids). 

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. 

FDG is readily taken tip by this transport system, although the extent of uptake can be influenced by the concentration of plasma glucose, which competes with FDG for uptake. The efficiency of transport across the blood brain barrier is such that blood flow is generally not limiting for tracer delivery but the potential for a drug to have a direct vascular effect that influences tracer delivery should be considered. 

GLUT 1 All tissues, especially red cells, brain 1-2 Basal uptake of glucose transport across the blood-brain barrier... 

Agus, D.B., et al. 1997. Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters. J Clin Invest 100 2842. 

The brain relies on the circulation for nutrients and is a chief consumer of glucose. The brain uses about 15 percent of the energy required for minimal maintenance of body functions (called the basal metabolic rate). Brain tissue doesn t store energy. Instead, the brain must rely on the circulation for its fuel supply. Not all molecules can be transported across the blood-brain barrier to be used for energy. One molecule that can cross the blood-brain barrier is glucose, the preferred fuel source for the brain. Brain tissue can also adapt to ketone bodies such as acetoacetate as a source of fuel. 

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