Brain capillary endothelial cells form theblood-brain barrier (BBB). They are connectedby extensive tight junctions, and arepolarized into luminal (blood-facing) andabluminal (brain-facing) plasma membranedomains. The polar distribution of transportproteins mediates amino acid (AA) homeostasisin the brain. The existence of two facilitativetransporters for neutral amino acids(NAA) on both membranes provides thebrain access to essential AA. Four Na+-dependent transporters of NAA exist in theabluminal membranes of the BBB. Togetherthese systems have the capability to activelytransfer every naturally occurring NAA fromthe extracellular fluid (ECF) to endothelialcells and thence to the circulation. The presenceof Na+-dependent carriers on the abluminalmembrane provides a mechanism bywhich NAA concentrations in the ECF ofbrain are maintained at about 10% of those of the plasma. Also present on the abluminalmembrane are at least three Na+-dependentsystems transporting acidic AA (EAAT)and a Na+-dependent system transportingglutamine (N). Facilitative carriers forglutamine and glutamate are found only inthe luminal membrane of the BBB. Thisorganization promotes the net removal ofacidic and nitrogen-rich AA from brain, andaccounts for the low level of glutamate penetrationinto the central nervous system (CNS).The presence of a g -glutamyl cycle at theluminal membrane and Na+-dependent AAtransporters at the abluminal membrane mayserve to modulate movement of AA fromblood to brain. The g -glutamyl cycle isexpected to generate pyroglutamate withinthe endothelial cells. Pyroglutamate stimulatessecondary active AA transporters at theabluminal membrane, thereby reducing netinflux of AA to the brain. It is now clear theBBB participates in the active regulation ofthe AA content of the brain.
|Original language||English (US)|
|Title of host publication||Amino Acids in Human Nutrition and Health|
|Number of pages||26|
|State||Published - Nov 24 2011|
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)