Amino acid transport across each side of the blood-brain barrier

R. A. Hawkins, J. R. Viña, D. R. Peterson, R. O'Kane, A. Mokashi, Ian Simpson

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Citations (Scopus)

Abstract

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 languageEnglish (US)
Title of host publicationAmino Acids in Human Nutrition and Health
PublisherCABI Publishing
Pages189-214
Number of pages26
ISBN (Print)9781845937980
StatePublished - Nov 24 2011

Fingerprint

blood-brain barrier
Blood-Brain Barrier
Brain
Amino Acids
amino acids
brain
Membranes
Neutral Amino Acids
Pyrrolidonecarboxylic Acid
Facings
Extracellular Fluid
Endothelial cells
extracellular fluids
Glutamic Acid
Neutral Amino Acid Transport Systems
Endothelial Cells
glutamates
endothelial cells
Acidic Amino Acids
Amino Acid Transport Systems

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hawkins, R. A., Viña, J. R., Peterson, D. R., O'Kane, R., Mokashi, A., & Simpson, I. (2011). Amino acid transport across each side of the blood-brain barrier. In Amino Acids in Human Nutrition and Health (pp. 189-214). CABI Publishing.
Hawkins, R. A. ; Viña, J. R. ; Peterson, D. R. ; O'Kane, R. ; Mokashi, A. ; Simpson, Ian. / Amino acid transport across each side of the blood-brain barrier. Amino Acids in Human Nutrition and Health. CABI Publishing, 2011. pp. 189-214
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Hawkins, RA, Viña, JR, Peterson, DR, O'Kane, R, Mokashi, A & Simpson, I 2011, Amino acid transport across each side of the blood-brain barrier. in Amino Acids in Human Nutrition and Health. CABI Publishing, pp. 189-214.

Amino acid transport across each side of the blood-brain barrier. / Hawkins, R. A.; Viña, J. R.; Peterson, D. R.; O'Kane, R.; Mokashi, A.; Simpson, Ian.

Amino Acids in Human Nutrition and Health. CABI Publishing, 2011. p. 189-214.

Research output: Chapter in Book/Report/Conference proceedingChapter

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N2 - 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.

AB - 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.

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Hawkins RA, Viña JR, Peterson DR, O'Kane R, Mokashi A, Simpson I. Amino acid transport across each side of the blood-brain barrier. In Amino Acids in Human Nutrition and Health. CABI Publishing. 2011. p. 189-214